Embryology - User contributions [en-gb]

Z3185685

2009-10-22T03:08:58Z

Z3185685:

== '''Lab 1 Questions''' ==

1)What is the protein that sperm binds to on the surface?
ZP3

2)Name the 3 stages of follicle development in the ovary.

- Primordial follicle
- Preantral follicle
- Antral follicle (Graafian)

----

--[[User:Z3185685|Sumaiya Rahman]] 13:08, 6 August 2009 (EST)
== '''Lab 2 Questions''' ==

1. What factor do the synctiotrophoblast cells secrete to support the ongoing pregnancy?

Human Chorionic Gonadotropin (hCG)

2. What does the corpus luteum secrete to prevent continuation of the menstrual cycle?

Progesterone

3. What are the 2 main tissues to be derived from the germ cell layer continuous with the lining of the amniotic sac?

Nervous tissue and epithelium of the skin

----
'''Links for group assignment'''

http://www.reproduction-online.org/cgi/reprint/48/1/43

http://books.google.com/books?id=RY0rXE2HgqsC&pg=PA344&dq=rabbit+embryo+stages&as_brr=3#v=onepage&q=rabbit%20embryo%20stages&f=false - good for what studies in rabbit embryo has been used for. And has a good table for embryological stages!!

http://books.google.com/books?id=ljAKtC-iIrIC&pg=PA264&dq=rabbit+embryo+stages&as_brr=3#v=onepage&q=rabbit%20embryo%20stages&f=false

http://books.google.com/books?id=73bbKzqRvLsC&pg=PA156&dq=rabbit+embryo+stages&lr=&as_brr=3#v=onepage&q=rabbit%20embryo%20stages&f=false - picture of implantation

http://books.google.com/books?id=aZ7DQYFyxswC&pg=PA122&dq=%22rabbit+development+stages%22&lr=&as_brr=3#v=onepage&q=&f=false

----

--[[User:Z3185685|Sumaiya Rahman]] 13:14, 13 August 2009 (EST)
== '''Lab 3 Questions''' ==

1. What period of human development (in weeks) do the 23 Carnegie stages cover? 8 weeks

2. What part of the somite will contribute to the vertebral column? The ventromedial component - sclerotome

3. At what Carnegie stage does the human neural tube normally completely close? Stage 13

----

--[[User:Z3185685|Sumaiya Rahman]] 13:57, 20 August 2009 (EST)
== '''Lab 4 Questions''' ==

1. Into what structure do most blood vessels empty before they enter the embryonic heart? The liver

2. What do the dorsal aortas become in the adult? The descending aorta

3. What are the layers of cells found in a tertiary villi?

----

--[[User:Z3185685|Sumaiya Rahman]] 14:13, 27 August 2009 (EST)
== '''Lab 5 Questions''' ==

1. What was the question I said in the respiratory lecture would be part of this week's assessment?

Is it more common for a congenital diaphragmatic hernia to happen on one side or both?

2. What is the answer to the above question?

It is more common for a diaphragmatic hernia to occur on one side. Majority (80%) occur on the left side.

----

--[[User:Z3185685|Sumaiya Rahman]] 13:59, 3 September 2009 (EST)

== '''Lab 6 Questions''' ==

1. Which is the more common clefting, cleft lip or cleft palate? Cleft lip is more common

2. What structures does pharyngeal pouch 1 form? tympanic membrane, tympanic cavity, mastoid antrum, auditory tube

3. Neural crest forms which cells within the skin? melanocytes

http://www.reproduction-online.org/cgi/reprint/125/4/479
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2694706

----

--[[User:Z3185685|Sumaiya Rahman]] 13:46, 17 September 2009 (EST)

== '''Lab 7 Questions''' ==

1. Briefly; what is a myotube and how is it formed?
- Elongated mulitinucleated cells that have peripherally located myofibrils.
- They are formed by a fusion of myoblasts during skeletal development and eventually develop into mature muscle fibres.

2. What changes would I expect to see in the muscle fibre types in my legs if I:

a) Suffered a spinal cord injury
-Muscle atrophy
-conversion of slow twitch muscle fibres to fast twitch muscle fibres.

b) Took up marathon running
-Conversion of fast twitch muscle fibres to slow twitch muscle fibres
----

--[[User:Z3185685|Sumaiya Rahman]] 13:32, 24 September 2009 (EST)

--[[User:Z3185685|Sumaiya Rahman]] 13:21, 1 October 2009 (EST)

MARK 4/5 SP

== '''Lab 10 Questions''' ==

* Question 1 - Identify and name 3 tissue types which contain adult (somatic) stem cells that were used/studied from the 5 articles discussed during the tutorial.
-Muscle, Bone marrow and adipose tissue

* Question 2 - Name 2 reprogramming strategies/methods used in generating human induced Pluripotent Stem Cells (iPSCs) from the 5 articles discussed during the tutorial.
Lentivirus, Virus-free integration - epizonal factors

* Question 3 - Is the following statement TRUE or FALSE?

"Unlike the nuclear genome, the mitochondrial DNA in the embryo is derived almost exclusively from the egg; that is, it is of maternal origin."
- TRUE

----
--[[User:Z3185685|Sumaiya Rahman]] 15:35, 8 October 2009 (EST)

--[[User:Z3185685|Sumaiya Rahman]] 14:41, 15 October 2009 (EST)
--[[User:Z3185685|Sumaiya Rahman]] 14:08, 22 October 2009 (EST)

Z3185685

2009-10-15T03:41:49Z

Z3185685:

Z3185685

2009-10-14T12:55:52Z

Z3185685: /* Lab 10 Questions */

Z3185685

2009-10-14T12:54:49Z

Z3185685: /* Lab 10 Questions */

== '''Lab 1 Questions''' ==

1)What is the protein that sperm binds to on the surface?
ZP3

2)Name the 3 stages of follicle development in the ovary.

- Primordial follicle
- Preantral follicle
- Antral follicle (Graafian)

----

--[[User:Z3185685|Sumaiya Rahman]] 13:08, 6 August 2009 (EST)
== '''Lab 2 Questions''' ==

1. What factor do the synctiotrophoblast cells secrete to support the ongoing pregnancy?

Human Chorionic Gonadotropin (hCG)

2. What does the corpus luteum secrete to prevent continuation of the menstrual cycle?

Progesterone

3. What are the 2 main tissues to be derived from the germ cell layer continuous with the lining of the amniotic sac?

Nervous tissue and epithelium of the skin

----
'''Links for group assignment'''

http://www.reproduction-online.org/cgi/reprint/48/1/43

http://books.google.com/books?id=RY0rXE2HgqsC&pg=PA344&dq=rabbit+embryo+stages&as_brr=3#v=onepage&q=rabbit%20embryo%20stages&f=false - good for what studies in rabbit embryo has been used for. And has a good table for embryological stages!!

http://books.google.com/books?id=ljAKtC-iIrIC&pg=PA264&dq=rabbit+embryo+stages&as_brr=3#v=onepage&q=rabbit%20embryo%20stages&f=false

http://books.google.com/books?id=73bbKzqRvLsC&pg=PA156&dq=rabbit+embryo+stages&lr=&as_brr=3#v=onepage&q=rabbit%20embryo%20stages&f=false - picture of implantation

http://books.google.com/books?id=aZ7DQYFyxswC&pg=PA122&dq=%22rabbit+development+stages%22&lr=&as_brr=3#v=onepage&q=&f=false

----

--[[User:Z3185685|Sumaiya Rahman]] 13:14, 13 August 2009 (EST)
== '''Lab 3 Questions''' ==

1. What period of human development (in weeks) do the 23 Carnegie stages cover? 8 weeks

2. What part of the somite will contribute to the vertebral column? The ventromedial component - sclerotome

3. At what Carnegie stage does the human neural tube normally completely close? Stage 13

----

--[[User:Z3185685|Sumaiya Rahman]] 13:57, 20 August 2009 (EST)
== '''Lab 4 Questions''' ==

1. Into what structure do most blood vessels empty before they enter the embryonic heart? The liver

2. What do the dorsal aortas become in the adult? The descending aorta

3. What are the layers of cells found in a tertiary villi?

----

--[[User:Z3185685|Sumaiya Rahman]] 14:13, 27 August 2009 (EST)
== '''Lab 5 Questions''' ==

1. What was the question I said in the respiratory lecture would be part of this week's assessment?

Is it more common for a congenital diaphragmatic hernia to happen on one side or both?

2. What is the answer to the above question?

It is more common for a diaphragmatic hernia to occur on one side. Majority (80%) occur on the left side.

----

--[[User:Z3185685|Sumaiya Rahman]] 13:59, 3 September 2009 (EST)

== '''Lab 6 Questions''' ==

1. Which is the more common clefting, cleft lip or cleft palate? Cleft lip is more common

2. What structures does pharyngeal pouch 1 form? tympanic membrane, tympanic cavity, mastoid antrum, auditory tube

3. Neural crest forms which cells within the skin? melanocytes

http://www.reproduction-online.org/cgi/reprint/125/4/479
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2694706

----

--[[User:Z3185685|Sumaiya Rahman]] 13:46, 17 September 2009 (EST)

== '''Lab 7 Questions''' ==

1. Briefly; what is a myotube and how is it formed?
- Elongated mulitinucleated cells that have peripherally located myofibrils.
- They are formed by a fusion of myoblasts during skeletal development and eventually develop into mature muscle fibres.

2. What changes would I expect to see in the muscle fibre types in my legs if I:

a) Suffered a spinal cord injury
-Muscle atrophy
-conversion of slow twitch muscle fibres to fast twitch muscle fibres.

b) Took up marathon running
-Conversion of fast twitch muscle fibres to slow twitch muscle fibres
----

--[[User:Z3185685|Sumaiya Rahman]] 13:32, 24 September 2009 (EST)

--[[User:Z3185685|Sumaiya Rahman]] 13:21, 1 October 2009 (EST)

MARK 4/5 SP

== '''Lab 10 Questions''' ==

--[[User:Z3185685|Sumaiya Rahman]] 15:35, 8 October 2009 (EST)

* Question 1 - Identify and name 3 tissue types which contain adult (somatic) stem cells that were used/studied from the 5 articles discussed during the tutorial.
-Muscle, Bone marrow and adipose tissue

* Question 2 - Name 2 reprogramming strategies/methods used in generating human induced Pluripotent Stem Cells (iPSCs) from the 5 articles discussed during the tutorial.
Lentivirus, Virus-free integration - epizonal factors

* Question 3 - Is the following statement TRUE or FALSE?

"Unlike the nuclear genome, the mitochondrial DNA in the embryo is derived almost exclusively from the egg; that is, it is of maternal origin."
- TRUE

Z3185685

2009-10-14T12:49:19Z

Z3185685: /* Lab 10 Questions */

== '''Lab 1 Questions''' ==

1)What is the protein that sperm binds to on the surface?
ZP3

2)Name the 3 stages of follicle development in the ovary.

- Primordial follicle
- Preantral follicle
- Antral follicle (Graafian)

----

--[[User:Z3185685|Sumaiya Rahman]] 13:08, 6 August 2009 (EST)
== '''Lab 2 Questions''' ==

1. What factor do the synctiotrophoblast cells secrete to support the ongoing pregnancy?

Human Chorionic Gonadotropin (hCG)

2. What does the corpus luteum secrete to prevent continuation of the menstrual cycle?

Progesterone

3. What are the 2 main tissues to be derived from the germ cell layer continuous with the lining of the amniotic sac?

Nervous tissue and epithelium of the skin

----
'''Links for group assignment'''

http://www.reproduction-online.org/cgi/reprint/48/1/43

http://books.google.com/books?id=RY0rXE2HgqsC&pg=PA344&dq=rabbit+embryo+stages&as_brr=3#v=onepage&q=rabbit%20embryo%20stages&f=false - good for what studies in rabbit embryo has been used for. And has a good table for embryological stages!!

http://books.google.com/books?id=ljAKtC-iIrIC&pg=PA264&dq=rabbit+embryo+stages&as_brr=3#v=onepage&q=rabbit%20embryo%20stages&f=false

http://books.google.com/books?id=73bbKzqRvLsC&pg=PA156&dq=rabbit+embryo+stages&lr=&as_brr=3#v=onepage&q=rabbit%20embryo%20stages&f=false - picture of implantation

http://books.google.com/books?id=aZ7DQYFyxswC&pg=PA122&dq=%22rabbit+development+stages%22&lr=&as_brr=3#v=onepage&q=&f=false

----

--[[User:Z3185685|Sumaiya Rahman]] 13:14, 13 August 2009 (EST)
== '''Lab 3 Questions''' ==

1. What period of human development (in weeks) do the 23 Carnegie stages cover? 8 weeks

2. What part of the somite will contribute to the vertebral column? The ventromedial component - sclerotome

3. At what Carnegie stage does the human neural tube normally completely close? Stage 13

----

--[[User:Z3185685|Sumaiya Rahman]] 13:57, 20 August 2009 (EST)
== '''Lab 4 Questions''' ==

1. Into what structure do most blood vessels empty before they enter the embryonic heart? The liver

2. What do the dorsal aortas become in the adult? The descending aorta

3. What are the layers of cells found in a tertiary villi?

----

--[[User:Z3185685|Sumaiya Rahman]] 14:13, 27 August 2009 (EST)
== '''Lab 5 Questions''' ==

1. What was the question I said in the respiratory lecture would be part of this week's assessment?

Is it more common for a congenital diaphragmatic hernia to happen on one side or both?

2. What is the answer to the above question?

It is more common for a diaphragmatic hernia to occur on one side. Majority (80%) occur on the left side.

----

--[[User:Z3185685|Sumaiya Rahman]] 13:59, 3 September 2009 (EST)

== '''Lab 6 Questions''' ==

1. Which is the more common clefting, cleft lip or cleft palate? Cleft lip is more common

2. What structures does pharyngeal pouch 1 form? tympanic membrane, tympanic cavity, mastoid antrum, auditory tube

3. Neural crest forms which cells within the skin? melanocytes

http://www.reproduction-online.org/cgi/reprint/125/4/479
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2694706

----

--[[User:Z3185685|Sumaiya Rahman]] 13:46, 17 September 2009 (EST)

== '''Lab 7 Questions''' ==

1. Briefly; what is a myotube and how is it formed?
- Elongated mulitinucleated cells that have peripherally located myofibrils.
- They are formed by a fusion of myoblasts during skeletal development and eventually develop into mature muscle fibres.

2. What changes would I expect to see in the muscle fibre types in my legs if I:

a) Suffered a spinal cord injury
-Muscle atrophy
-conversion of slow twitch muscle fibres to fast twitch muscle fibres.

b) Took up marathon running
-Conversion of fast twitch muscle fibres to slow twitch muscle fibres
----

--[[User:Z3185685|Sumaiya Rahman]] 13:32, 24 September 2009 (EST)

--[[User:Z3185685|Sumaiya Rahman]] 13:21, 1 October 2009 (EST)

MARK 4/5 SP

== '''Lab 10 Questions''' ==

--[[User:Z3185685|Sumaiya Rahman]] 15:35, 8 October 2009 (EST)

* Question 1 - Identify and name 3 tissue types which contain adult (somatic) stem cells that were used/studied from the 5 articles discussed during the tutorial.
-Muscle, Bone marrow and adipose tissue

* Question 2 - Name 2 reprogramming strategies/methods used in generating human induced Pluripotent Stem Cells (iPSCs) from the 5 articles discussed during the tutorial.

* Question 3 - Is the following statement TRUE or FALSE?

"Unlike the nuclear genome, the mitochondrial DNA in the embryo is derived almost exclusively from the egg; that is, it is of maternal origin."
- TRUE

Z3185685

2009-10-14T12:44:00Z

Z3185685: /* Lab 10 Questions */

== '''Lab 1 Questions''' ==

1)What is the protein that sperm binds to on the surface?
ZP3

2)Name the 3 stages of follicle development in the ovary.

- Primordial follicle
- Preantral follicle
- Antral follicle (Graafian)

----

--[[User:Z3185685|Sumaiya Rahman]] 13:08, 6 August 2009 (EST)
== '''Lab 2 Questions''' ==

1. What factor do the synctiotrophoblast cells secrete to support the ongoing pregnancy?

Human Chorionic Gonadotropin (hCG)

2. What does the corpus luteum secrete to prevent continuation of the menstrual cycle?

Progesterone

3. What are the 2 main tissues to be derived from the germ cell layer continuous with the lining of the amniotic sac?

Nervous tissue and epithelium of the skin

----
'''Links for group assignment'''

http://www.reproduction-online.org/cgi/reprint/48/1/43

http://books.google.com/books?id=RY0rXE2HgqsC&pg=PA344&dq=rabbit+embryo+stages&as_brr=3#v=onepage&q=rabbit%20embryo%20stages&f=false - good for what studies in rabbit embryo has been used for. And has a good table for embryological stages!!

http://books.google.com/books?id=ljAKtC-iIrIC&pg=PA264&dq=rabbit+embryo+stages&as_brr=3#v=onepage&q=rabbit%20embryo%20stages&f=false

http://books.google.com/books?id=73bbKzqRvLsC&pg=PA156&dq=rabbit+embryo+stages&lr=&as_brr=3#v=onepage&q=rabbit%20embryo%20stages&f=false - picture of implantation

http://books.google.com/books?id=aZ7DQYFyxswC&pg=PA122&dq=%22rabbit+development+stages%22&lr=&as_brr=3#v=onepage&q=&f=false

----

--[[User:Z3185685|Sumaiya Rahman]] 13:14, 13 August 2009 (EST)
== '''Lab 3 Questions''' ==

1. What period of human development (in weeks) do the 23 Carnegie stages cover? 8 weeks

2. What part of the somite will contribute to the vertebral column? The ventromedial component - sclerotome

3. At what Carnegie stage does the human neural tube normally completely close? Stage 13

----

--[[User:Z3185685|Sumaiya Rahman]] 13:57, 20 August 2009 (EST)
== '''Lab 4 Questions''' ==

1. Into what structure do most blood vessels empty before they enter the embryonic heart? The liver

2. What do the dorsal aortas become in the adult? The descending aorta

3. What are the layers of cells found in a tertiary villi?

----

--[[User:Z3185685|Sumaiya Rahman]] 14:13, 27 August 2009 (EST)
== '''Lab 5 Questions''' ==

1. What was the question I said in the respiratory lecture would be part of this week's assessment?

Is it more common for a congenital diaphragmatic hernia to happen on one side or both?

2. What is the answer to the above question?

It is more common for a diaphragmatic hernia to occur on one side. Majority (80%) occur on the left side.

----

--[[User:Z3185685|Sumaiya Rahman]] 13:59, 3 September 2009 (EST)

== '''Lab 6 Questions''' ==

1. Which is the more common clefting, cleft lip or cleft palate? Cleft lip is more common

2. What structures does pharyngeal pouch 1 form? tympanic membrane, tympanic cavity, mastoid antrum, auditory tube

3. Neural crest forms which cells within the skin? melanocytes

http://www.reproduction-online.org/cgi/reprint/125/4/479
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2694706

----

--[[User:Z3185685|Sumaiya Rahman]] 13:46, 17 September 2009 (EST)

== '''Lab 7 Questions''' ==

1. Briefly; what is a myotube and how is it formed?
- Elongated mulitinucleated cells that have peripherally located myofibrils.
- They are formed by a fusion of myoblasts during skeletal development and eventually develop into mature muscle fibres.

2. What changes would I expect to see in the muscle fibre types in my legs if I:

a) Suffered a spinal cord injury
-Muscle atrophy
-conversion of slow twitch muscle fibres to fast twitch muscle fibres.

b) Took up marathon running
-Conversion of fast twitch muscle fibres to slow twitch muscle fibres
----

--[[User:Z3185685|Sumaiya Rahman]] 13:32, 24 September 2009 (EST)

--[[User:Z3185685|Sumaiya Rahman]] 13:21, 1 October 2009 (EST)

MARK 4/5 SP

== '''Lab 10 Questions''' ==

--[[User:Z3185685|Sumaiya Rahman]] 15:35, 8 October 2009 (EST)

* Question 1 - Identify and name 3 tissue types which contain adult (somatic) stem cells that were used/studied from the 5 articles discussed during the tutorial.

* Question 2 - Name 2 reprogramming strategies/methods used in generating human induced Pluripotent Stem Cells (iPSCs) from the 5 articles discussed during the tutorial.

* Question 3 - Is the following statement TRUE or FALSE?

"Unlike the nuclear genome, the mitochondrial DNA in the embryo is derived almost exclusively from the egg; that is, it is of maternal origin."

Talk:2009 Group Project 1

2009-10-14T12:40:08Z

Z3185685: /* Actual Changes Made */

== Lab 10 ==
--[[User:Z3283499|Antonio Lee]] 10:52, 2 October 2009 (EST) Hi everyone, I will be working with you during the Lab10 Tutorial and here is the news link and PDF of the manuscript for your group exercise. I encourage you to read the paper before the tutorial. Also, please indicate next to the questions below (using either your initials or student number) which one of the four questions you wish to address.
:'''Group 1 :''' [http://www.nature.com/nature/journal/v461/n7262/full/461354a.html '''Developmental biology: Asexual healing'''] in Nature News and Views - Nature 461, 354-355 (17 September 2009) [[Media:ANAT2341_Lab10_2009_Group 1 Reading.pdf|Manuscript (PDF): Mitochondrial gene replacement in primate offspring and embryonic stem cells]]

:Question 1. What is the background to the existing problem / disease condition? --[[User:Z3187802|Vishnnu Shanmugam]] 22:12, 2 October 2009 (EST)

Mitochondria are found in all eukaryotic cells and contain their own genome (mitochondrial DNA or mtDNA). Unlike the nuclear genome, which is derived from both the egg and sperm at fertilization, the mtDNA in the embryo is derived almost exclusively from the egg; it is of maternal origin.

Mutations in mitochondrial DNA (mtDNA) can lead to a range of chronic incurable diseases such as myopathies, neurodegenerative diseases, diabetes, cancer and infertility. Mutations in mitochondrial DNA could also contribute to other diseases such as Alzheimer’s,
Parkinson’s and Huntington’s diseases

A normal cell should be homoplasmic in its mitochondrial DNA, that is it should only contain one type of mitochondrial DNA. But if the cell has two or more types of mitochondrial DNA (a mixture of normal and mutated DNA) it is known as heteroplasmic and can lead to a range of diseases. These genetic mutations can also be passed to offspring causing disease.
1 in 3,500–6,000 are at risk or presently have a disorder from mutations in mitochondrial DNA. Disease progresses slowly and there are no cure. Limitations in assessing the extent heteroplasmy and accuracy in calculating the risks of developing mtDNA related disease means that a new approach is needed to tackle the problem.

:Question 2. What approach / method did the research team take to tackle / improve the problem?--[[User:Z3126328|Jin Lee]] 12:31, 7 October 2009 (EST)
:Working with rhesus macaque monkeys, the authors reconstructed mature oocytes containing the nuclear genome from one oocyte and the mitochondrial genome from another. To do this they removed the nuclear genetic material from one oocyte, leaving behind all of the mitochondrial DNA, then transferred it to another oocyte whose nucleus had been removed (a cytoplast), but which contained a full complement of mitochondrial DNA.

:Question 3. What was the breakthrough / major advancement OR failure / drawback? and why might this be of significance?
::Drawbacks - --[[User:Z3186093|Jenny Guy]] 22:43, 7 October 2009 (EST)
:::There were difficulties in visualising and isolating the intact chromosomes, as well as the mtDNA being susceptible to damage and translocation/movement. Visualization became easier after the development of techniques for DNA staining with fluorophores and looking under UV light during embryo cloning by the SCNT (somatic cell nuclear transfer). Successful implementation to avoid damage to the cytoplast during spindle removal involved using polarized microscopy. (p368) --[[User:Z3186093|Jenny Guy]] 14:12, 8 October 2009 (EST)
:Question 4. What are the next steps in moving forward? What are the next or new hurdles to overcome?

==Actual Changes Made==

'''Concise Version:''' (Everyone add their changes here)
# Removed cleft palate and cleft lip section (Abnormal development) --[[User:Z3187802|Vishnnu Shanmugam]]
# Altered references (current research and abnormal development) --[[User:Z3187802|Vishnnu Shanmugam]]
# Added picture guide for transgenic rabbit --[[User:Z3187802|Vishnnu Shanmugam]]
# Added picture guide for rabbit cloning --[[User:Z3187802|Vishnnu Shanmugam]]
# Removed newspaper image of rabbit (Current research) --[[User:Z3187802|Vishnnu Shanmugam]]
# Formatted pictures and text to reduce gaps in the assignment (current research and abnormal development) --[[User:Z3187802|Vishnnu Shanmugam]]
# Corrected spelling mistakes in images (current research and abnormal development) --[[User:Z3187802|Vishnnu Shanmugam]]
# Reviewed all images and have written a summary, original source, copyright information (current research and abnormal development) --[[User:Z3187802|Vishnnu Shanmugam]]
# Formatted the look of the genetics section, including 'abnormalities' --[[User:Z3186093|Jenny Guy]] 16:31, 14 October 2009 (EST)
# Fiddled with position of images in genetics section --[[User:Z3186093|Jenny Guy]] 16:31, 14 October 2009 (EST)
# Fixed spelling mistake in History - Jin Lee
# Added images in table of stages. --[[User:Z3185685|Sumaiya Rahman]]
# Added to introduction and related it to the rest of the page. --[[User:Z3185685|Sumaiya Rahman]]
# Scale added to diagram of relative sizes of rabbit embryo --[[User:Z3185685|Sumaiya Rahman]]

'''Long Version:'''

--[[User:Z3187802|Vishnnu Shanmugam]] 23:46, 10 October 2009 (EST) Okies, all done. I'm going to review all my images and add summaries to them. Dr. Hill asked for a concise version to all the changes we make from the peer review process. I suggest everyone add their changes to the list I have started above and place your signature next to it.

--[[User:Z3186093|Jenny Guy]] 14:29, 10 October 2009 (EST)Hey vishnuu, i was thinking could you please alter
* the gaps between the spina bifida images (format this somehow with the images on the side and text on the other)
* the gap under "Brachydactylia & Acheiropodia"...maybe you have entered down too much????
cheers :)

--[[User:Z3187802|Vishnnu Shanmugam]] 21:27, 9 October 2009 (EST)Hey all. I have removed the newspaper image of rabbit (Due to copyright issues), and have replaced it with a series of images that guides the reader through the process of cloning a rabbit. I have NOT altered the text summarizing the creation of transgenic and clone rabbits as there are very important & detailed information which if removed puts complex processes in danger of oversimplification. I also corrected spelling mistakes in some images.

--[[User:Z3187802|Vishnnu Shanmugam]] 20:22, 7 October 2009 (EST) Hey gang. By popular demand (or the stress of reading) people want less text. I have removed the entire cleft palate & cleft lip section from abnormal development. For current research, I have also created a step by step picture guide for transgenic rabbit creation. It was initially meant to be a video, but this wiki page does not display (.gif) or (.mov) files. Sum, I remember that you did your references after me...so when I removed the cleft palate & cleft lip section, the references changed....so I have also adjusted your references accordingly. I don't think it is necessary to make all the changes outlined below as most comments are subjective (different people have different preferences) and seems like some comments were made because people had nothing else to propose.

--[[User:Z3126328|Jin Lee]] 10:01, 8 October 2009 (EST)Hi Guys, I have fixed spelling mistake and some people commented to make table form for advantages and disvantages section. But I liked the way I presented so I will leave in point form.

--[[User:Z3186093|Jenny Guy]] 14:32, 8 October 2009 (EST)
Hey! I looked at what i could change in the genetics section and decided to format a little. Our peers asked:
* genome information into a table - this is a little silly since there'd only be one column.
* Reformating in sections such as hitory and genetics. - have tried to do a little.
* Make pictures appear on the same side of page. maybe aligning the pics on either the left or right side instead of both left and right, and possibly putting them as thumbnails could also work. - i tried to put both of the chromosome images ont he same side (tried both left and right) but found that it looked terrible considering the size (which is needed to see it) as the text wouldnt fit around it very well.
* it will look much better if there is some work to be done for the structure of it especially the paragraph under the heading of 'abnormalities'. - am still in the process. not sure what else i can do since its in basic dot point form with not a large text to format. any ideas? or shall i leave it how it is now?
* maybe instead of writing the entire reference, you could just state The Broad Institute or just the people related to it - i feel that the entire team needs a mention since all people relate to it. noting just the broad institute is almost like noting a team of people here in unsw as just plainly "UNSW" which is just disrespectful.

==Things to work on noted by peers==

Hey, So the changes i will make will be in the introduction section. Also a lot of people have said to add pictures in the stages section to make it more interesting. I couldnt get permission to use the images so i bought tracing paper today! lol will try to draw them and see if they are ok enough to add. I think i am going to leave the timeline section as is because most people liked it. What do u guys think? --[[User:Z3185685|Sumaiya Rahman]] 15:31, 8 October 2009 (EST)

Sounds great Sum....Its gonna take some effort to trace it then scan it. GL --[[User:Z3187802|Vishnnu Shanmugam]] 21:37, 9 October 2009 (EST)

Hey guys,
I read through all the notes our peers have given us and summarised them into the following sections. Majority of them overlap (where ive put a new persons opinions in the same dot point over and over to stress the point on how many people noticed). Some things are easily changed, most of all i reckon its
# formatting
# pictures
# text to be more concise
So we just need to finalise all these minor things to improve our project. Please detail any changes you've made in the the heading above.
Cheers, --[[User:Z3186093|Jenny Guy]] 20:30, 7 October 2009 (EST)

INTRODUCTION
* a little too brief, more information needed
* For the first sentence (the characteristics that make the rabbit an excellent model for study), mention the section 'Why are we using rabbits?' under History section.
* For the second sentence (study that developed and improved micromanipulation techniques), mention the 'Transgenic Rabbit' section below under the genetics section. I've read the entire project page, and the introduction was the only place I found that was not precise enough (which is a great thing). These are minor things, but I think they will help with improving your project page.
*suggestion: Place the history section after the Introduction. This gives the viewer an overview of the use of the rabbit embryo. This way the viewer is first subjected to a few examples of the rabbit embryos use. It also allows him/her to understand where the rabbit embryo sits in with history. I guess this is a matter of personal preference.

HISTORY
* The advantages and Disadvantages would be better in a table. the history you might want to put the advantages and disadvantages into a table to make the page look a bit more tidy and easier to read when we go through it.
* The usage of rabbits for experimental models in science and medicine could be stated under the history section to allow background information for the readers to become aware of the topic and why the rabbit have been used to study specfic medical procedures and diseases.
* Spelling mistake under 'Discovery of Graafian Follicle', 2nd paragraph. I think it's previous instead of 'previcous'.
* Reformating in sections such as hitory and genetics. Make pictures appear on the same side of page.
* The history section can be improved if the infomation is expanded to give some more detailed background knowledge although i like the idea that the information is concise describing each scientists contribution towards the model.
* could be formatted to make the information stand out and a lot more appealing, I would recommend including pictures if possible that link to the text and making the advantages and disadvantages into a table rather than listing it.

TIMELINE
* more images to wholly understand. timeline/staging section was clear and concise, however it could be improved by adding more colour/pictures to maintain the readers' interest. The timeline and staging bits are very well written and clear but i think you should add a few images in there to match up with the text. Perhaps some pictures of embryos throughout development. Pictures for every stage would make it more visually attractive rather than just reading text. lack of pics in the timeline.
* It’s a little confusing that the development jumps back and forth according to the body part developing. Maybe it should be categorised according to time of development instead for greater clarity at first glance
* The timeline is just a little confusing, as its divided into development of different parts, which breaks the time flow.
* some of the information for the timeline section was too heavy for the page - would recommend only using some of the information on your actual page and having the rest as links to separate pages

STAGING
* pictures for stages would have been nice, unless there were none????
* a more even distribution of information, particularly more detail in the stages
* Provide pictures for individual stages. Get visual, and make the stages interesting to read. include pictures in the stages section.
* Staging section is also very well presented but the information presented in a table would even look better if there is use of some pictures to make it more interesting for its audience.
* staging section was very bland and would be more appealing with pictures. I dont think its necessary to cite your entire reference within the text

GENETICS
* genome information into a table
* Reformating in sections such as hitory and genetics.
* Make pictures appear on the same side of page. maybe aligning the pics on either the left or right side instead of both left and right, and possibly putting them as thumbnails could also work.
* it will look much better if there is some work to be done for the structure of it especially the paragraph under the heading of 'abnormalities'.
* maybe instead of writing the entire reference, you could just state The Broad Institute or just the people related to it

ABNORMAL DEVELOPMENT
* There is also a lot of content which might be alleviated by reducing the section on abnormal development. Too much information about the abnormalities. make more concise.
* the abnormalities went a bit over board, and didn't need that much attention I think (as compared witht the research which was good)
* reduce the writing content. for example. In the current research section, you have two scientific process of transgenic rabbits as well as cloning which is described in how these are done. why not draw a step by step diagram, and put these written steps in the link to the image.
* The information provided under Hydrocephalus and Brachydactylia was informative and interesting, but it contained too much text. I suggest you narrow it down and make use of Dots point, numbering, bold/italic words, and/or sub-sub-headings.
* Section for "Abnormal Development" gives the readers useful amount of information but i think its very lenghty, use of dot points can make it look even better and easy to understand.

CURRENT RESEARCH
* the group makes good usage of diagrams but towards the end diagrams die out, you might want to make the current research part of your assignment into diagrams and steps as there is just a bunch of information thrown there and alot of reading needed, if you put it into steps or diagrams it will make the marking process and reading process easier and allow us as reader to understand the information with ease.
* 'Transgenic Rabbit' should be shifted toward the genetic information on the rabbit. (Jenny - i dont agree with this as its research, not its offical genetics. Vishnnu - Neither do I)
* information in regard to stem cells should be brief and truncated. Example in regard to stem cell research should have brief and simple model explaining the process and why it used.
* There is too much information under stem cells. There is 2 examples of studies dealing with stem cells. A suggestion would be to just have one, and have a link saying 'Koga's research on Stem Cells'.
* Have the section 'links to Research labs and researchers' placed at the end of current research. That way, the information on the page will flow smoother.
* more of a focus on current research i.e. what each method is being used for and less on the process behind each method.
* great amount of information but in my perspective replacing the paragraphs with some dot points with heading and subheadings would further enrich understanding of readers.

OVERALL
* "As you start going down the page though the information starts to read a bit haphazardly, for example the developing body; jumping for section to section and the timeline section. it would be great if you could clean this up as it doesn't really flow." - formatting
* condense long slabs of text as the page is long
* format it so there are no huge gaps
* move the links to current research labs up closer to the current research section, just to keep it all together

==Constructive Criticism of Coordinator==
--[[User:S8600021|Mark Hill]] 08:07, 8 October 2009 (EST) The following comments are general in nature in no specific order, as it would be inappropriate to suggest specific changes and then assess the final project. Comments will be added during this week and you still have one week before final submission.

* There is no concise list of changes made to your project on the basis of peer assessments.
* Timeline of Embryo Development early stages, are in the introductory text said to be in hours, but it would be good to see it in the list as well.
* [[:File:Sizes.JPG]] Relative sizes, but no absolute size or scale given.
* A general comment about images. When you click an image and it opens, the information below the image should have an explanation of what the image shows, a reference (if from a paper) and a link to the original source (if available) as well as copyright information.
* Did you actually read the terms of use for this image that you cut n pated into the image description? [[:File:Rabbit_hybrid.jpg]] "For this purpose alone you may retrieve and display the Content on a computer screen. You may also print out, but not photocopy, one copy of individual files on paper and store files in electronic form on disc, but not on any server or any other storage device connected to a network where the Content could be accessed by other users." It clearly states that you cannot use this image online.
* Chromosomes section, images have no legends and structure not clearly organised.
* There needs to be better checking of your spelling and grammar, for example [[:File:Rabbitmalformation3.jpg]] "Plant Patkology of Tke Rockefeller Institute for Medical Researck", these mistakes while not major, suggests a lack of reviewing of your work by the group.
* Just a comment on project "feel", when several people work together on a project and insert their parts, the final project sometimes has an uneven style. Now that you have time to tidy up, try and get a common appearance throughout your project.

==Constructive Criticism of Peers==

--[[User:Z3218657|Sally Clarke]] 09:32, 1 October 2009 (EST)
Nice work Guys!
- Fantastic images used throughout - maybe a few more in the timeline so we can understand what is going on
- As you start going down the page though the information starts to read a bit haphazardly, for example the developing body; jumping for section to section and the timeline section. it would be great if you could clean this up as it doesn't really flow.
- The section on the abnormal development is great.
- The page is quite long - Maybe you could condense some of the text as it is kind of slab like
- i really enjoyed the breeding section
- The advantages and Disadvantages would be better in a table.

--[[User:Z3223194|Bronwyn Lewis-Jones]] 08:08, 1 October 2009 (EST) Hi Group 1! This is obviously a well organised and well researched assignment. I found it very informative. There are (of course) some things I feel could improve the overall submission. I loved that the timeline/staging section was clear and concise, however I think it could be improved by adding more colour/pictures to maintain the readers' interest. There is also a lot of content which might be alleviated by reducing the section on abnormal development. Hope this helps :)

--[[User:Z3218146|Julianna Lam]] 01:11, 1 October 2009 (EST) good job guys.
-Theres alot of relevant information.
-The timeline and staging bits are very well written and clear but i think you should add a few images in there to match up with the text.
-The image for the genetics bit is awesome.
-The page is nicely set out.
-Too much information about the abnormalities.

--[[User:Z3258567|Sando Rashed]] 20:04, 30 September 2009 (EST)hey guys, your page looks good, starts off well as there is not a bunch of information just thrown in, the information used is well thought, with the history you might want to put the advantages and disadvantages into a table to make the page look a bit more tidy and easier to read when we go through it (you can also do this with the info under genome), the group makes good usage of diagrams but towards the end diagrams die out, you might want to make the current research part of your assignment into diagrams and steps as there is just a bunch of information thrown there and alot of reading needed, if you put it into steps or diagrams it will make the marking process and reading process easier and allow us as reader to understand the information with ease, other than that the page looks quite good, well done on all your contributions

--[[User:Z3218792|Gabriela Pinget]] 21:51, 29 September 2009 (EST)

Nice page. I particularly liked the idea of lists of what is to come before each flood of information as was done with the ‘history of model use’ section.

- Nice easing into the topic with ‘advantages’ and ‘disadvantages’ lists.

- I liked the of rabbit embryo development to that of humans- puts it into perspective

- Good glossary- informative but not over- the- top

- Nice genetics section! Easy to read and a great use of illustrations to break up the information

- I also like that you took a page out of Mark’s book in the addition of the abnormalities section

Improvements:

- Perhaps some pictures of embryos throughout development.

- It’s a little confusing that the development jumps back and forth according to the body part developing. Maybe it should be categorised according to time of development instead for greater clarity at first glance

--[[User:Z3295026|Joe Nassif]] 17:01, 29 September 2009 (EST)

Your assessment has come along great in regard to the criteria format. There are a few alterations that could improve your project, the following alterations may enhance your wiki page:

'''-''' The usage of rabbits for experimental models in both science and medicine could be state under the history section to allow background information for the readers to become aware of the topic and why the rabbit have been used to study specfic medical procedures and diseases.

'''-''' Secondly the information on 'Transgenic Rabbit' should be shifted toward the genetic information on the rabbit. So far the project is looking and coming along great except for minor edits.

'''-''' Background information should be placed subsequent to the introduction allowing the reader to understand why this specific animal is used for specfic purposes.

'''-''' Figures/Graphs and the illustration of the anatomy and genetic development of the embryo were useful and clear allowing the viwers to understand and learn through the demonstration of pictures which were extremely informative.

'''-''' Genetics: the Genetics and Abnormalities information was great and very informative. It was great how the group compared the embryo with the human chromosome allowing the audience to understand the difference between both.

'''-''' Abnormalities: Information and details which were in the genetic section provided informative and interesting information, and it could be truncated a bit, additionally just discussing the chromosome development of the rabbit.

'''-''' Current Embryology Research: information in regard to stem cells should be brief and truncated. Example in regard to stem cell research should have brief and simple model explaining the process and why it used.

'''-''' Consequently, I thought the project was good it flowed and was very informative. The information was detailed, and the illustrations were useful and allowed the readers to gain a brief overview on the topic and it usage in history and in current research. Overall group 1 seem to achieve the critriea outcomes and summarised the topic really well, the comparsion to human embryo development througout the text was great and is a good referencing point in comparsion to the species choosen.
Great job --[[User:Z3295026|Joe Nassif]] 17:01, 29 September 2009 (EST)

--[[User:Z3255007|Sadaf Masood]] 12:09, 30 September 2009 (EST)Hello Group 1! Congrats on your awesome group project! I must say im very impressed with all the information you have posted and i have listed down the good bits and the bits that need to be improved. Since i am posting this a lil late, i have seen that u have already improved your project and few aspects...Good Job guys!

1. Very brief introduction...maybe just a little bit more info will be perfect

2. Abnormalities section is very informative and well researched, but very long, how about making it a little more precise?

3. The Advantages and Disadvantages of the using Rabbit is just simply perfect

4. The timeline is just a little confusing, as its divided into development of different parts, which breaks the time flow.

5. Pictures for every stage would make it more visually attractive rather than just reading text

6. Great Glossary!

There were few things earlier that need to be improved but you guys fixed it as soon as comments were posted so basically you guys rock :)An excellent effort guys. Best Wishes

# --[[User:Z3217015|Mitchell Mathieson]] 09:45, 25 September 2009 (EST)Very nice. The information was maybe a bit spread out, with heaps of gaps everywhere (formatting???), but the information was there, and relevant, and easy to read. I like how there was tonnes of information on current research, as I think that was the main aim, but the abnormalities went a bit over board, and didn't need that much attention I think. pictures for stages would have been nice, unless there were none???? The references are top notch, and the glossary is pretty amazing, and in the right place. Overall very good, I think formatting was the major downfall though, as it makes the page that much longer, and hence a little bit more difficult to read.

--[[User:Z3224449|Elide Newton]] 14:12, 26 September 2009 (EST)
HEllO GROUP 1: Well done on such a great assignemnt, looks like you have all worked very hard. Well my one point of constructive criticism would be to reduce the writing content. for example. In the current research section, you have two scientific process of transgenic rabbits as well as cloning which is described in how these are done. why not draw a step by step diagram, and put these written steps in the link to the image. that way it is more visual, the info is still there under the image link, and the page wont look as daunting to read. :) hope this helps!

--[[User:Z3254857|Begum Sonmez]] 00:46, 26 September 2009 (EST)
Hello Group 1. Firstly, I would like to let you all know that you have all done a great job. I'm impressed. I have a few suggestions that I think mite help to improve the page even more:

*Introduction:

1)For the first sentence (the characteristics that make the rabbit an excellent model for study), mention the section 'Why are we using rabbits?' under History section.

2)For the second sentence (study that developed and improved micromanipulation techniques), mention the 'Transgenic Rabbit' section below under the genetics section. I've read the entire project page, and the introduction was the only place I found that was not precise enough (which is a great thing). These are minor things, but I think they will help with improving your project page.

3)Breeding information was informative.

4) A suggestion: Place the history section after the Introduction. This gives the viewer an overview of the use of the rabbit embryo. This way the viewer is first subjected to a few examples of the rabbit embryos use. It also allows him/her to understand where the rabbit embryo sits in with history. I guess this is a matter of personal preference.

*Timeline:

1)Graphs, and the illustration of the zona pellucida and mucin coat were very clear and informative.

*Staging: I had no problems with it. The lack of information I think was a plus. It touched on the content in the Timeline section.

*History:

1) I loved the idea of the 'Disadvantages' of the rabbit embryo, it seemed unbiased. The brief timeline provided a clear and short summary.

2) Spelling mistake under 'Discovery of Graafian Follicle', 2nd paragraph. I think it's previous instead of 'previcous'. Also, the 2nd paragraph under this heading does not flow that well. Try rephrasing the 2nd sentence.

*Genetics:

The Genetics and Abnormalities section flow into eachother very well. I appreciated the comparison of the rabbit chromosome to the human chromosome.

*Abnormalities:

1) The information provided under Hydrocephalus and Brachydactylia was informative and interesting, but it contained too much text. I suggest you narrow it down and make use of Dots point, numbering, bold/italic words, and/or sub-sub-headings.

*Current Embryology Research:
1) There is too much information under stem cells. There is 2 examples of studies dealing with stem cells. A suggestion would be to just have one, and have a link saying 'Koga's research on Stem Cells'.

2) Have the section 'links to Research labs and researchers' placed at the end of current research. That way, the information on the page will flow smoother.

Overall, I thought there was a consistent structure in each section. The information was informative, and the pictures were relevant and helped me better understand the topics of discussion.

--[[User:Z3252340|Emily Wong]] 10:58, 27 September 2009 (EST) Firstly, great work. It is a well researched, structured and organised page. The content is very in depth and includes information on all of the specified areas. It is well referenced, with an extensive reference list indicating the amount of research put into the page. Some areas are more detailed than others. For example, the staging section is quite short and concise where as the Abnormal development section is extremely long considering it is not a needed topic. There is moderate use of pictures and diagrams, but more use could benefit the page as it may be able to negate some of the large slabs of text. The comparisons made between the human and the rabbit embryos are a good part of the project page. Each member of the group has contributed to the page and provided a lot of information on the section of content they were working on. What would improve this project is a more even distribution of information, particularly more detail in the stages, a few more diagrams or pictures to negate some of the text presented, more of a focus on current research i.e. what each method is being used for and less on the process behind each method.

--[[User:Z3126345|Gang Liu]] 14:26, 27 September 2009 (EST)In my opionion, this is a well constructed page. It includes major subheadings such as history, timeline, stages, genetics and current research. It is very concise and straightforward, which makes it easy to read. For example, a short introduction paragraph,"...the rabbit is an appropriate animal model as the results from many experiments are significant to that of other mammals, including humans.", explains to reader why rabbit is such a suitable model.

It also provides a logic flow. For example, in history of rabbit model use section, it has provided advangtages and disadvantages of model use. This is appropriate, as it demonstrates the significance of rabbit model use in scitific discovery. In addition, it has provided detailed background information for each discovery. This makes it interesting to read.

It is also important to compare development of embryo between rabbit and human. For example, "... the similarities of this developmental pattern in humans and rabbits, suggests that the same growth increment is required to achieve the same stage. The main difference observed between human rabbit gestational duration is due to the fetal growth phase...", this has suggested human and rabbit share many similarities. Not only this page has demonstrated detailed written information of timeline development, it also provided graphics to reinforce the concept. For example, the hand drawing of developing embryo. As well as the comparison between human embryo and rabbit embryo timeline development.

It is also interesting to learn that rabbits have 22 pairs of chromosome, whereas humans have 23 pairs of chromosome.

Sections such as abnormal development and current research have demonstrated extended research and understanding. For example, hydrocephalus, spina Bifida, stem cell research and cloning techniques. All of these have showed the in depth research in textbooks, journals and internet based literatures.

However, this page can be improved by considering the following points.

*Provide pictures for individual stages. Get visual, and make the stages interesting to read.

*Reformating in sections such as hitory and genetics. Make pictures appear on the same side of page.

*Typo: "A rabbits potential for reproduction..."

*Sections such as abnormal development and current research are too lengthy. Might consider shrink the content.

*Lack of glossary.

Overall, big thumbs up!

--[[User:Z3252231|Angama Yaquobi]] 01:12, 28 September 2009 (EST)
First of all i would like to congratulate all the team members for a great team work.
Well done guys!! The group project looks amazing, the information presented is very concise
and straight to the point which makes it very easy for the readers to grab
the important information that they need to enhance their knowledge.
I like the section of history, the information is very clear,
and i like the idea of providing some background knowledge to the readers
about the disadvantages of the use of rabbit.
The history section can be improved if the infomation is expanded
to give some more detailed background knowledge althought
i like the idea that the information is concise describing each
scientists contribution towards the model.
The section for timeline is impressive, in my perspective its a great idea to cover alot of content in a very smart way
which is by the use of subheadings to make it easy to understand for audience.
Staging section is also very well presented but the information presented
in a table would even look better if there is use of some pictures
to make it more interesting for its audience. Genetics section
is beautifully presented, all the information is there with some
amazing pictures but will look much better if there is some work to
be done for the structure of it especially the paragraph under the
heading of 'abnormalities'. Section for "Abnormal Development" gives
the readers useful amount of information but i think its very lenghty,
use of dot points can make it look even better and easy to understand.
The same for Current embryology research, great amount of information but
in my perspective replacing the paragraphs with some dot points with
heading and subheadings would further enrich understanding of readers.
Also glossary would complement the webpage. But overall,
great amount of information which shows alot of research
which has been done by all the team members. Well done guys!!

--[[User:Z3217686|Thomas Dangerfield]] 13:29, 28 September 2009 (EST) Hey guys! Good work on your assignment! Plenty of info which is good, and very well referenced. The glossary is a good idea too! I do agree with a few others about the lots of clear spaces in the formatting, and the lack of pics in the timeline though. Also under the genetics section, maybe aligning the pics on either the left or right side instead of both left and right, and possibly putting them as thumbnails could also work. In the abnormalities section, there might have been a little too much info that probably wasn't needed, but i do like the effort put in. Over all, possibly more time spent on formatting and determining which sections are more important and which sections may need to be limited. Other than those points, the whole assignment seemed very well done!

--[[User:Z3215682|Carly Mooney]] 11:32, 29 September 2009 (EST)
You assignment is visually appealing and the genetic information e.g. the number of chromosomes of a rabbit was very interesting.There are some additional sections you have added which really complement your assignment e.g the abnormalities and I really liked the advantages and disadvantages of using the rabbit model. The few suggestions I would make is to:
* include pictures in the stages section
*place the pictures throughout the text (e.g. to left or right). You did this up until abnormalities and I felt it broke the flow of the written text.
* and maybe move the links to current research labs up closer to the current research section, just to keep it all together.
Overall very impressive though.

--[[User:Z3220040|Joanne Raffel]] 15:25, 29 September 2009 (EST) Nice wikipage, the page looked interesting however I agree with some others that the formatting of the page was inconsistent. I thought the referencing was great but found it a bit confusing with the reference numbers after the paragraphs. I thought the subheadings werent distinct enough, especially in relation to the text, which made it difficult to read. The history section could be formatted to make the information stand out and a lot more appealing, I would recommend including pictures if possible that link to the text and making the advantages and disadvantages into a table rather than listing it. I especially liked the comparison between the rabbit and the human embryo, however some of the information for the timeline section was too heavy for the page, I would recommend only using some of the information on your actual page and having the rest as links to separate pages. The staging section was very bland and would be more appealing with pictures. I dont think its necessary to cite your entire reference within the text, especially in the genetics section, maybe instead of writing the entire reference, you could just state The Broad Institute or just the people related to it. The abnormalities section was a good inclusion however it was very extensive, along with the current research section. Overall a very good wikipage.

----
*Hey, Well done guys!!! I think our group worked pretty well! I think we communicated each other well and did very best for their section. I fixed my spelling mistake and problem with sentence! As Begum mentioned, I think placing the history part after the introduction is better idea. --[[User:Z3126328|Jin Lee]] 13:36, 26 September 2009 (EST)

*Hey guys,
the project has come together brilliantly! it looks quite good. Hopefully mark will like it! ill add some terms to the glossary and try do some formatting (the first image is a little too big i think!) --[[User:Z3186093|Jenny Guy]] 10:28, 24 September 2009 (EST)

Hey. Yep all good. I had to get rid of the pics, so stages table is now blank. Im pretty much done. I'll see what i can add to the glossary. thanks :)--[[User:Z3185685|Sumaiya Rahman]] 23:34, 23 September 2009 (EST)

Hey all, I'm going to start a glossary and add it under the reference section. Scan your text and add to the glossary in alphabetical order. Also under the marking criteria, it says to provide links to researchers and research laboratories.....i'll start that under the glossary. Everyone else OK with their stuff?--[[User:Z3187802|Vishnnu Shanmugam]] 23:08, 23 September 2009 (EST)

Hey Sum, The images look fine but I don't think you can use the images like that since the journal KARGER is being particular about its copyright laws. I tried tracing around the images but it does not seem to resemble anything like an embryo. I did however find this link...go to it and scroll down to the images of the developing embryo. You might be able to edit it to resemble rabbit embryo. --[[User:Z3187802|Vishnnu Shanmugam]] 15:10, 23 September 2009 (EST). To get to the link, Google image search "rabbit gestation"....click on the "rabbit,gestation age" image from nature.com
Also google image search "The Haeckel embryo sequence"...could be useful after some editing

oh my god!! I summarised all of my research and wrote down on the page. Then I blew up everything!!!
it says 'edit conflict' what da?? I lost all of my work...it was my stupid mistake...--[[User:Z3126328|Jin Lee]] 01:06, 23 September 2009 (EST)

Oh also.. let me know if the images look stupid --[[User:Z3185685|Sumaiya Rahman]] 00:34, 23 September 2009 (EST)

Hey thanks vishnuu. I put some images up in the stages table. I did edit the pictures, but im not sure if im allowed to use it like this? have a look and let me know. Also im not sure what is going on with the reference section seems kinda all over the place, so i havnt added mine in yet. Maybe we should fix that up somehow? :) oh LOL about the breeding rabbits bit! haha
--[[User:Z3185685|Sumaiya Rahman]] 00:31, 23 September 2009 (EST)

Hey Sum, Sorry for the late reply. For $330, I'd rather breed rabbits and take the photos myself. I had a look at the original images, what we can do is trace around the developing rabbit embryo using the pencil tool on an image editing software(eg. microsoft paint - already preloaded into most windows). Then upload the image to the assignment. Does your PC have adobe fireworks?...extremely good for tracing images. If not, have a go at it with microsoft paint....I shall also have a go at it, then I shall let you know on this discussion page at about 3PM t'morrow. If any good then I'll send it to your student email. If not, we discuss potential alternatives. good luck Sum! --[[User:Z3187802|Vishnnu Shanmugam]] 23:51, 22 September 2009 (EST)

Yep thats the article i used for the developmental stages and put in a table. I should have my timeline posted by end of today. I also couldn't get permission to use the pictures as they wanted about $330 for me to use it!! no thanks. I'll see if i can work it in somehow. Vishnuu did u have any ideas on editing the images?? --[[User:Z3185685|Sumaiya Rahman]] 12:29, 22 September 2009 (EST)

Have a look at this article, it's helpful for comparison bt rabbit and human in developmental stages!--[[User:Z3126328|Jin Lee]] 13:35, 21 September 2009 (EST)
*Sampled rabbit embryos were staged using the Carnegie criteria, in order first to determine if they were consistent with the rabbit developmental pattern, and second to compare this pattern with the human one. Our results show a suitable '''comparison of rabbits and humans in early developmental stages''', except for the neural growth.
[http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowAbstract&ArtikelNr=73136&Ausgabe=229537&ProduktNr=224239
]

Absolutely correct Juliana, my research articles and their links are labelled 1-6 so far, the rest is yours..... I'll fix it for you. A timeline image seems tricky and i'm unsure, send Dr. Hill an email on m.hill@unsw.edu.au and see what he says. We still have till thursday to finish everything, so don't be too worried....try to finish all your other stuff and leave the drawing of the timeline last.--[[User:Z3187802|Vishnnu Shanmugam]] 17:49, 20 September 2009 (EST)

*no.1-7 in reference section is mine. and I think links under Vishnnu's research on the discussion board is mine. let me know please. (I can't remember all of my researches)
I want to make a timeline image but I can't do it;;; I asked Mark few weeks ago but havn't replied yet....can somebody help me???--[[User:Z3126328|Jin Lee]] 17:26, 20 September 2009 (EST)

'''** Hey Jenny, dont worry!! the project is not due until next week! (24th) we will have it done by then!! I am still waiting for permission to use the pictures in my stages section, thats why it hasnt been done yet. Hopefully i can get permission, otherwise i'll have to draw them (or something) myself.''' --[[User:Z3185685|Sumaiya Rahman]] 14:03, 17 September 2009 (EST)

It says project due date 24th september.......if the due date had been brought forward why was it not posted on the project main page? --[[User:Z3187802|Vishnnu Shanmugam]] 13:48, 17 September 2009 (EST)

EVERYONE...WHY IS THE REST OF OUR PROJECT NOT DONE??
* vishnuu...its due TODAY!! how can you post things up next Monday? Please make sure youve referenced EVERY image and all text (i know youve said you need to do this...but its easiest done when writing the section as now you have to go back and find everything, insert numbers etc. Remember to put the reference in the reference section. For the current research section i thought this might help you (as during my lecture in another class they spoke about how rabbits are used in heart development. Is there anything that you've found to include this?). Also I found this website during my research so it may help you? [http://www.evergen.com/rabbit_experience.html/ Rabbit Experiments]
* sum - where is the timeline???? It doesn't exist? Where is it? Also, we need some sort of visual for the staging. Have you found an images? Could you draw the stages of embryo development? It just looks incredibly boring.
* julianna...you need to put up more other than just two historians...there is NO referencing whatsoever in your entire section. where have you found this information? have you put it in your own words or copied it? You need to add some more refences to the reference section at the bottom..there just aren't many to back up your research.

seriously guys. ive added photos and tried to spice up the project but i am NOT going to finish your sections for you. ITS DUE IN 3 HRS! i cant believe you guys haven't bothered to even try finish this. Im very disappointed and i think its slack to let the team down. --[[User:Z3186093|Jenny Guy]] 10:34, 17 September 2009 (EST)

----

Hey all, just need to finish editing the current research part before i post it up, also need to edit some of my images under abnormal development and also references. Should be all done by Monday. --[[User:Z3187802|Vishnnu Shanmugam]] 07:02, 17 September 2009 (EST)

--[[User:S8600021|Mark Hill]] 01:40, 8 September 2009 (EST) OK guys, this is still just a page of text......

--[[User:Z3126328|Jin Lee]] 14:50, 3 September 2009 (EST) I want to make a timeline?

--[[User:S8600021|Mark Hill]] 08:42, 21 August 2009 (EST) z3187802 has contacted me and has been away sick. He should still complete his components of the group project.

Our group is Sum, Vishnnu, Juliana and Jenny. Today in the lab we have decided to research the RABBIT! [http://embryology.med.unsw.edu.au/OtherEmb/Rabbit.htm/ Rabbit embryology from Mark Hill]

(Juliana's email belebele85@msn.com)

----
This is apparently what we need to include in our case study:
#Timeline of Embryo Development - how long (SUM)
#Staging - are there species specific staging, what occurs when (SUM)
#History of Model Use - when was it first used, (JULIANNA)
#Genetics - chromosome number, sequencing (JENNY)
#Abnormal Development (VISHNNU)
#Current Embryology Research - research papers and findings (VISHNNU)

Hey guys, maybe we should add a section comparing rabbit to human development
--[[User:Z3185685|Sumaiya Rahman]] 16:45, 6 August 2009 (EST)

That sounds like a good idea Sum....seeing that human development is the primary theme of the course, not including it would be criminal!. -vishnnu

Report:
* Links to resources and discussions are to be posted on the group talk page, the project page is for the actual assignment
* Final assignment will be marked by another group and everyone will be given a marking criteria
* No information should be obtained from Wikipedia and all information (tables & graphs included) must be referenced
* Please feel free to suggest any further topics which can be included

== Research: ==
So i think the main rabbit used in research is the oryctolagus cuniculus. Lets focus mostly on that (or at least i, Jenny, will since im going genetics). This link is great for the specific genetics: [http://www.ncbi.nlm.nih.gov/nuccore/AJ001588/ Oryctolagus cuniculus complete mitochondrial genome]

Here's some stuff about benefits of modeling from a textbook. I haven't yet written as my own so its still the authors material. Just thought it might benefit us all (and raise our morale as we thought the rabbit might suck..but it doesn't!) We're not "submitting" this as our own work so technically we're not yet copyrighting their material.
Ive cited the book here and the website i got it from:
[http://books.google.com.au/books?id=RY0rXE2HgqsC&pg=PA344&lpg=PA344&dq=rabbit+embryology+genetics&source=bl&ots=rbr3CuBRxY&sig=p8055w9oYQmsQeuN78mgXBGmRK4&hl=en&ei=NI2KStaQJIvSsQOEpMjEDQ&sa=X&oi=book_result&ct=result&resnum=3#v=onepage&q=&f=false/ Cibelli, J., Lanza, R., Campbell, K. and West, M. 2002. Principles of Cloning. Academic Press]

“Rabbits were one of the first species in which blastomere nuclear transfer succeeded; as a model species, rabbits placed a central role in developing the micromanipulation technologies in embryos.” Other advantages for using rabbits are:

# “The costs to animal procurement, animal care, and oocyte production in rabbits are relatively low compared to large animals.” e.g. a cow embryo is 30x more expensive that a rabbit embryo
# “The developmental biology of rabbit embryos and fetuses resembles more closely that of large farm animals than that of rodent model species, including the transition from maternal to embryonic control of embryo development.”
# “The pregnancy of rabbits is relatively short (1 month), allowing rapid evaluation of fetal and postnatal development. In comparison, the gestation length for cattle is 9x longer.”
# “The sizeable milk production of rabbits allows their use as test animals for therapeutic protein expression in milk, or as a living bioreactor.”
# “Rabbits are induced ovulators. Domesticated rabbits are nonseasonal breeders and produce multiple offspring in one litter. These reproductive patterns make the use of rabbits for reproductive research highly efficient.”

----
Here are some links i (sum) found which may help. Need to go through all the info and sort it out, But there are a couple of good diagrams.

'''Links for group assignment'''

http://www.reproduction-online.org/cgi/reprint/48/1/43

http://books.google.com/books?id=RY0rXE2HgqsC&pg=PA344&dq=rabbit+embryo+stages&as_brr=3#v=onepage&q=rabbit%20embryo%20stages&f=false - good for what studies in rabbit embryo have been used for. And has a good table for embryological stages!!

http://books.google.com/books?id=ljAKtC-iIrIC&pg=PA264&dq=rabbit+embryo+stages&as_brr=3#v=onepage&q=rabbit%20embryo%20stages&f=false

http://books.google.com/books?id=73bbKzqRvLsC&pg=PA156&dq=rabbit+embryo+stages&lr=&as_brr=3#v=onepage&q=rabbit%20embryo%20stages&f=false - picture of implantation

http://books.google.com/books?id=aZ7DQYFyxswC&pg=PA122&dq=%22rabbit+development+stages%22&lr=&as_brr=3#v=onepage&q=&f=false
-------
Hi I(Juliana) uploaded file, you guys can have a look.
Go to 'Upload File' tab and click ' early growth of rabbit trophoblast' file.

-------------
also I found an interesting article!
'''An Electron Microscope Study of the Embryology of the Intercalated Disc in the Heart of the Rabbit'''
Alan R. Muir
The Journal of Biophysical and Biochemical Cytology, Vol. 3, No. 2 (Mar. 25, 1957), pp. 193-202
Published by: The Rockefeller University Press

http://info.library.unsw.edu.au/cgi-bin/local/access/ej-access.cgi?url=http://links.jstor.org/sici?origin=sfx%3Asfx&sici=0095-9901(1957)3%3A2%3C193%3AAEMSOT%3E2.0.CO%3B2-S
--

[[User:Z3126328|Jin Lee]] 10:48, 25 August 2009 (EST)

----------------
I found helpful book in the library
'''Bensley's Practical Anatomy of the Rabbit 8thE by E.Horne Craigie, Toronto, University of Toronto Press 1948'''
--[[User:Z3126328|Jin Lee]] 13:27, 27 August 2009 (EST)

==Vishnnu's Research==

'''Background reading (Vishnnu)'''

Hey everyone. I'm starting my background reading section where I shall describe my research resources. They contain a summary and a link to the resource itself. I shall keep this "notes" section updated with each new entry I add.

'''Notes:'''

*Articles 1 & 2 - Juliana this could be useful to you.

*Article 2 - Sum this could be useful to you.

*Articles 3 & 4 - Abnormal development articles (added: 02/09/2009)

*Articles 5 & 6 - Abnormal development articles (added: 13/09/2009)

'''Article 1'''

'''The rabbit as a model for reproductive and developmental toxicity studies''' --[[User:Z3187802|Vishnnu Shanmugam]] 21:05, 30 August 2009 (EST)

''Robert H. Foote and Edward W. Carney'' ''Reproductive Toxicology 14 (2000) 477–493'' ''Department of Animal Science, Cornell University, 204 Morrison Hall, Ithaca, New York 14853-4801, USA Developmental and Reproductive Toxicology, ''The Dow Chemical Company Midland, Michigan 48674, USA''

'''Summary'''

This is a review article of a study looking at the use of rabbits in toxicological studies. The article describes the advantages in using the rabbit experimental model as opposed to the rodent model (mice & rats) and outlines the differences that make toxicological studies on rabbit embryos more accurate than rodents to resemble similar toxicological effects in human embryos. The article describes various techniques that can be used (eg. blood collection from marginal ear vein, artificial insemination, embryo collection) and solutions to some common problems that researchers face when using animal models. Very interesting article with a great quote from Robert Koch to open the eyes of researchers to other animal models:

“Gentlemen, never forget that mice are not human beings”

Want to find out more? Follow the link!

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6TC0-41SBGDH-1&_user=37161&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_acct=C000004218&_version=1&_urlVersion=0&_userid=37161&md5=4db60dc9352996fc4865b9d781b0128d

'''Article 2'''

'''Developmental stages in the rabbit embryo: guidelines to choose an appropriate experimental model''' --[[User:Z3187802|Vishnnu Shanmugam]] 21:05, 30 August 2009 (EST)

''S. Beaudoin; P. Barbet; F. Bargy''
''Fetal Diagnosis and Therapy; Nov/Dec 2003; 18, 6; Academic Research Library''
''pg. 422''

'''Summary'''

The article describes the various stages in the developing rabbit embryo and the rationale for using rabbits to study normal and abnormal embryology. The article details normal developments in the rabbit embryo and compares it to the developing human embryo. By making this comparison the article argues for the validity of rabbit embryology to better understand human embryology and also suggests that due to the similarities in the developing rabbit and human embryos, experiments on rabbit embryo’s yield more reliable results for human embryology. The article has some rare images on normally developing rabbits and breaks the developmental stages down (in days) describing the observable characteristics that form (eg. Limb development & body formation).
I have decided to use the image provided in the journal.

Definitely worth reading people, follow the link!

http://content.karger.com/produktedb/produkte.asp?typ=fulltext&file=FDT2003018006422

'''Article 3'''

'''Acheiropodia is caused by a genomic deletion in C7orf2, the human orthologue of the Lmbr1 gene''' --[[User:Z3187802|Vishnnu Shanmugam]] 04:32, 2 September 2009 (EST)

''P. Ianakiev, M. J. van Baren, M. J. Daly, S. P. A. Toledo, M. G. Cavalcanti, J. Correa Neto, E. Lemos Silveira, A. Freire-Maia, P. Heutink, M. W. Kilpatrick, P. Tsipouras''
''Am. J. Hum. Genet. 68:38–45, 2001''
''Department of Pediatrics, University of Connecticut Health Center, Farmington, CT;''
''Department of Clinical Genetics, Erasmus University, Rotterdam;''
''Whitehead Institute for Biomedical Research, Cambridge, MA;''
''LIM/25-D, University of Sao Paulo School of Medicine,''
''And Private Practice, Sao Paulo;''
''Private Practice, Porto Alegre, Brazil;''
''Department of Genetics, UNESP-Universidade Estadual Paulista, Botucatu SP, Brazil''

'''Summary'''

The article describes the developmental abnormality Acheiropodia can be passed down genetically from parent to offspring. Acheiropodia (also known as Horn Kolb Syndrome) is a condition where the distal extremities of the embryo fail to form. Although it is not fatal, the individual endures a very difficult life without hands and feet. The article notes that the disorder only affects the development of the limbs and has no other reported manifestations. The article defines this to be an autosomal recessive disorder which means that two copies of an abnormal gene must be present in the affected individual in order for the disease to develop. Thus, each parent passes an abnormal gene to the offspring. It is interesting to note the process of the malformation from genotype to phenotype: small deletions on the chromosomes produce abnormal genes, the abnormal genes are then passed down to the offspring, the offspring that inherits two of the abnormal genes is unable to code for the correct proteins and as a result, there is failure in normal development of limb extremities in the embryo phenotype. The article also has a shocking image of an individual with Acheiropodia which highlights the extent to which it can impact a person’s life and the urgent need to find a cure.

Read more about the exact nature of the abnormal gene using the link.

http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=1109034

'''Article 4'''

'''Epidemiology of congenital clefts of the lip and palate''' --[[User:Z3187802|Vishnnu Shanmugam]] 04:32, 2 September 2009 (EST)

''JOHN C. GREENE'' ''D.M.D. ,M.P.H.'' ''Public Health Rep. 1963 July; 78(7): 589–602''

'''Summary'''

This review article combines research to study the factors causing the developmental abnormalities cleft palate and cleft lip in populations. “Cleft palate (palatoschisis)” and “cleft lip (cheiloschisis)” are the terms used to describe the non- fusion of the upper lip, hard or soft palate and typically occur during the gestation phase of embryonic development. The article tables the occurrence of cleft palate and cleft lip in populations of people in various cities across the world. It also compares the occurrence of cleft palate and cleft lip in males and females. The article finds that the incidence of cleft palate and cleft lip is:

*Is random in males and females (ie. Occurs approximately evenly in both sexes)

*Is random in people living in different cities

*Is higher in children of mothers over the age of 35

*Is higher in white populations and lower in the negro populations which suggests possible role of environmental factors

*No concrete proof that cleft palate and cleft lip is hereditary

*Is higher in rats exposed to radiation and those fed riboflavin

*Is higher in rabbits and other lab animals exposed to higher stress through cortisone injections

Although the article is now quite ancient, it is interesting to note the incidence of cleft palate and cleft lip among people. It also shows the historical foundation of research into the causes of cleft palate and cleft lip through animal experimentation.

Read more about cleft palate epidemiology using the link.

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1915191

'''Article 5'''

'''Chromosome abnormalities in human embryos''' --[[User:Z3187802|Vishnnu Shanmugam]] 00:10, 13 September 2009 (EST)

''Santiago Munne & Jaques Cohen The Center for Reproductive Medicine and science of Saint Barnabas Medical Center, New Jersey, USA Human Reproductive Update 1998, Vol. 4, No. 6 pp. 842-855 European Society of Human Reproduction and Embryology''

'''Summary'''

As the title suggests, this article focuses on chromosomal abnormalities in the developing human embryo. To understand this article, it is necessary to first establish some basic definitions that are used throughout the article. Aneuploidy can be defined as the occurrence of one or more extra or missing chromosomes leading to an unbalanced chromosome number. Although most babies with an unbalanced amount of chromosomal material miscarry during the first trimester of pregnancy, those that are born have crippling conditions such as:

* Birth defects

* Turner's syndrome (disorder where a female child is born with only 1 X chromosome)

* Down's syndrome (disorder where child is born with 3 copies of chromosome 21)

* Edward's syndrome (disorder where child is born with 3 copies of chromosome 18)

* Patau's syndrome (disorder where child is born with 3 copies of chromosome 13)

* Klinefelter's syndrome (disorder where male child is born with 2 copies of the X chromosome and 1 Y chromosome)

Polyploidy is a type of aneuploidy where the baby has three, four, or more sets of chromosomes instead of the two present in diploids. Chromosomal mosaicism is when different cells within an individual, who has developed from a single fertilized egg, have a different chromosomal makeup. Most commonly there will be some cells with a typical number of chromosomes (46 chromosomes) and other cells with an altered number or structure of chromosomes.

The article explores the possible causes of chromosomal abnormalities resulting from pregnancy though techniques such as IVF (In-Vitro Fertilization) and ICSI (Intracytoplasmic Sperm Injection). It also analyses the role of FSH (follicle stimulation hormone), temperature, water and light in chromosomal abnormalities.

The article finds:

* High FSH concentration increases likelihood of chromosomal abnormalities

* ICSI & IVF techniques have increased likelihood of chromosomal abnormalities

* Chromosomes exhibit temperature sensitivity and changes in temperature can cause chromosomal abnormalities

Although the article makes a number of findings, it is yet to be backed up with convincing evidence; the article has some really cool images of the developing embryo soon after fertilization. Overall, an interesting read.

Interested? Follow the link!

http://humupd.oxfordjournals.org/cgi/reprint/4/6/842.pdf

'''Article 6'''

'''Evaluation of the Safety and Pharmacokinetics of the Multi-Targeted Receptor Tyrosine Kinase Inhibitor Sunitinib During Embryo–Fetal Development in Rats and Rabbits''' --[[User:Z3187802|Vishnnu Shanmugam]] 00:10, 13 September 2009 (EST)

''S. Patyna, J. Haznedar, D. Morris, K. Freshwater, G. Peng, J. Sukbuntherng, G. Chmielewski, and D. Matsumoto''
''Pfizer Global Research and Development, San Diego, California''
''Roche LLC, Palo Alto, California''
''Pfizer Global Research and Development, Kalamazoo, Michigan''
''Xenoport Inc., Santa Clara, California''
''Pfizer Global Research and Development,'' ''Groton, Connecticut '' ''Birth Defects Research (Part B) 86:204–213 (2009)''

'''Summary'''

The article looks at how toxicity affects embryo-fetal development. The article describes the abnormal changes that occur when Sunitinib (an oral inhibitor of multiple receptor tyrosine kinases) is administered to pregnant rabbits and rats. This experiment was performed in an attempt to mirror the effects of antiangiogenic agents used in cancer treatment. Sunitinib is an antiangiogenic agent and the use of antiangiogenic agents is not recommended for treating cancer in pregnant patients because of the potential harm to embryo-fetal development. Angiogenesis (the formation of blood vessels) plays a critical role in embryo–fetal development and antiangiogenic agents slow down and/or stop the formation of blood vessels in order to control cancer and stop its spread. In pregnant patients however, this has the potential to adversely affect the developing embryo and these adverse effects is what is investigated in this article.

The article finds the antiangiogenic agent Sunitinib at toxic levels can result in:

* Embryo death

* Fetal skeletal malformations including vertebrae malformation and cleft lip/palate

* Teratogenic effects in rabbits

* Decreased maternal and fetal body weight

This article is a recent study and provides important findings regarding the use of antiangiogenic agents, especially during pregnancy. Although the maternal effects are minimal, the adverse effects to the embryo are significant and permanent. The article makes good use of tables and graphs to juxtapose pieces of information and to show trends. It is very interesting to note the extent to which chemicals can impact the vulnerable developing embryo.

Read more at link. (Use institutional login from UNSW computers)

http://www3.interscience.wiley.com/journal/122262246/abstract?CRETRY=1&SRETRY=0

------
thank you so much Vishnuu~~^^ from Juliana
-----
I also changed the format if you guys dont mind--[[User:Z3126328|Jin Lee]] 18:33, 31 August 2009 (EST)
----

Hey '''Vishnuu''', that link you found with the stages is awesome! thanks so much. Do you know if i am allowed to use the embryo pics in that article on our wiki page?? i'm not sure about the copyright rules. It says at the bottom of the article "Reproduced with permission of the copyright owner. Further reproduction prohibited without permission."
Does this mean we can only provide a link to it on our page? if so that's a shame, because those pics were fantastic!! '''SUM'''

Oh i also added an introduction - sum

Hey Sum,
Unfortunately, since its copyright protected we can't use the image directly......but there is a way of getting around it....You can modify the image using picture editing tools, then simply reference where the original picture came from and state that it has been modified by you. Alternatively, you can trace around the picture and provide only an outline (this will be very difficult to do with detailed pictures, a good picture editing software is recommended). Either way according to whats written under '''editing basics''' we need to include a picture that has been drawn up ourselves in the project. Also, not sure if you are aware, but the project is NOT due on Thursday (3rd September), Dr. Hill has very generously given everyone an extension till after mid-session break. --[[User:Z3187802|Vishnnu Shanmugam]] 02:35, 2 September 2009 (EST)

==Julianna's Research==
[http://netvet.wustl.edu/species/rabbits/rabtmodl.txt]
HISTORY OF THE RABBIT (IN RESEARCH)

A. Discovered in Spain about 100 B.C.
B. Domesticated in the 1500's
C. Standardization of breeds in 1800's
1. Research Uses
a. 1852: Rabbits have DL-hyoscyamine
(a) Can survive belladonna
(b) Endogenous atropine esterase
b. 1884: Pasteur develops rabies vaccine
c. 1891: Heape performs embryo transfer
(a) Influence on phenotype of the
uterine environment
d. 1908: Ignatowsky produces atherosclerosis
(a) Fed diets of milk, meat, and
eggs
(b) Produced intimal lesions
(c) Believed lesions due to protein
e. 1928: Demonstrated intranuclear development
of herpes virus
f. Graafian follicle was first observed
g. Coat colors and Mendelian inheritance
h. Immunology studies
i. Testing of human use products
j. Basic science studies
k. Diagnostic requirements
l. Eye Research
m. Pyrogen testing
n. Fetal drug induced teratology
o. Parasite research

LITERATURE REVIEW OF RABBIT USE

A. 1956 to 1800 ... Over 8000 citations
B. 1966 to 1987 ... 130,000 citations linking the rabbit to
all areas of research
C. 1988 to present ... 821 citations under the search
criteria: Rabbit: Model: Human Disease
D. Numbers of Rabbits Used (APHIS; ILAR records 1989)

1967 504,500
1978 439,986
1982 547,312
1983 466,810
1984 529,101
1985 544,621
1986 521,773
1987 534,385

ADVANTAGES OF USING RABBITS
A. Provides repeatability of animal model studies
B. Large enough for single samples
C. Many stocks/strains as animal models
D. Easily managed
E. Quality of immunologic products
F. Ease of reproductive control

DISADVANTAGES OF USING RABBITS
A. Most colonies are a storehouse of diseases
B. Extremely variable to responses to general anesthetics

[http://www.ncbi.nlm.nih.gov/pubmed/18430597]
The rabbit as a model to study asthma and other lung diseases.Keir S, Page C.
Sackler Institute of Pulmonary Pharmacology, Division of Pharmaceutical Sciences, 5th Floor Hodgkin Building, King's College London, Guy's Campus, London SE1 9RT, UK.

No single animal model is able to reproduce all the features of human asthma. However, the similarities between neonatally immunised rabbits and human asthma highlight the value of this model in the investigation of asthma pathophysiology and in the development of therapeutic agents. Airway inflammation and airway responses to various stimuli including histamine, adenosine 5'monophosphte and antigen in allergic rabbits have shown similarities with the responses observed in asthmatics. Furthermore, functional studies in rabbit airways show they are poorly responsive to capsaicin as are human airways. Chronic pre-treatment with capsaicin desensitises the TRPV(1) receptor enabling studies into the effect of this drug in both rabbits and man. The allergic rabbit model has been used extensively in assessing the various classes of anti-asthma drugs and is sensitive to similar drugs as patients with asthma, including beta-adrenoceptor agonists, corticosteroids, phosphodiesterase inhibitors and theophylline. This article highlights the usefulness of the rabbit as a species to study lung biology.

[http://www.ncbi.nlm.nih.gov/pubmed/8447943]
Effects of strain and embryo transfer model (embryos from one versus two donor does/recipient) on results of cryopreservation in rabbit.Vicente JS, García-Ximénez F.
Departamento de Ciencia Animal, Universidad Politécnica de Valencia, Spain.

Differential effects of 2 transfer models for normal thawed embryos of 1 donor doe were studied on the offspring rate and their embryo survival at birth from 3 selected rabbit strains (SY and SB: synthetic strains, NZ: New Zealand White). Morulae were obtained 64-66 h post-coitum from 93 adult does treated with 25 IU of hCG (SY:36, NZ:27, SB:30). Morphologically normal morulae were frozen in the presence of 1.5M DMSO and stored in liquid nitrogen. Normal thawed embryos were transferred into the oviducts of synchronized recipient does of the same strain 48 h after being injected with 25 IU of hCG (SY:28, NZ:21, SB:24). Each recipient received embryos from 1 (single transfer) or 2 different donor does (double transfer). Significant differences were observed in the post-thawing percentage of normal embryos between strains (SY:95 +/- 1% and SB:85 +/- 3%, P < 0.05; NZ: ,91 +/- 2%). After transfer, no significant differences were observed in pregnancy rate and offspring rate between the transfer models, whereas significant differences were only found in survival rate when all transfers were analyzed (double: 24 +/- 4% vs single: 14 +/- 3%, P < 0.05). An effect of strain was detected in the pregnancy rate (NZ: 33% vs SB: 71%, P < 0.05; SY: 61%) and in the survival rate per donor doe on pregnant recipient doe (SY: 42 +/- 5 vs SB: 19 +/- 5, P < 0.05; NZ: 34 +/- 7%). These results suggest a differential embryo sensitivity with respect to their genetic origin in both the freezing-thawing and transfer procedures.

--[[User:Z3126328|Jin Lee]] 13:06, 3 September 2009 (EST)

[http://www.ncbi.nlm.nih.gov/pubmed/14064965?log$=activity]GROSS EFFECTS ON RABBIT EMBRYOS AND MEMBRANES OF X-IRRADIATION IN THE BLASTOCYST STAGE.

[http://www.ncbi.nlm.nih.gov/pubmed/11139224?ordinalpos=408&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum]Onset of zygotic transcription and maternal transcript legacy in the rabbit embryo.Brunet-Simon A, Henrion G, Renard JP, Duranthon V.
Laboratoire de Biologie du Développement, INRA, Jouy en Josas Cedex, France.

Onset of zygotic transcription is progressive from the one-cell stage onward in the rabbit embryo. Maternal transcripts remain fairly stable until the 8-16 cell stage when major transcriptional activation of the zygotic genome takes place. To understand the mechanisms of the maternal-to-zygotic transition in the genetic information governing development, we asked whether a progressive synthesis of zygotic transcripts takes over the maternal molecules, or whether the synthesis of zygotic transcripts is very abrupt and independent of the persistence of the maternal counterparts. To answer this question, we set up mRNA differential display experiments comparing the mRNA content of rabbit embryos at different stages during the preimplantation period. We isolated eight zygotic transcripts whose synthesis is abruptly turned on at the 8-16 cell stage. These transcripts are involved in general cellular metabolism and their maternal counterparts are still present up to the four-cell and even the 8-16 cell stage. This identification of early zygotic transcripts suggests that global long range modifications of chromatin structure result in a rapid increase in transcription rates during the major transcriptional activation of the zygotic genome.

[http://www.ncbi.nlm.nih.gov/pubmed/11245264?ordinalpos=409&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum]
Reconstruction of the heteroparental diploid condition in rabbit zygotes by nuclear transfer.Escribá MJ, García-Ximénez F.
Departamento de Ciencia Animal Universidad Politécnica de Valencia, Spain. mescriba@dca.upv.es

Studies on genomic imprinting showed that parental genomes have complementary roles during embryogenesis, are both essential and need to be synchronized in their embryonic stage for successful development to term. To our knowledge, these studies have not been performed in species other than mice. We studied the in vitro and in vivo development of reconstructed zygotes by combining female haploid nuclear donors and androgenetic hemizygous recipients. Haploid donor embryos at the 8- or 32-cell stage were obtained from electroactivated young rabbit ova (eight pulses maximum, consisting of 0 6 kVcm(-1) for 60 microsec each, 38 min apart) which were further cultured for 24 h or 32 h. Couplets formed by both the haploid male hemizygous recipients and haploid female donor cells were electrofused (2.2 kVcm(-1) for 60 microsec duration each, 30 min apart) and their nuclear configuration determined 122 of those fused (43%: 122/286) were diploid. Reconstructed diploid zygotes developed in vitro up to the compacted morula, blastocyst and hatched stages (1/8-nuclei x 50%, 18% and 9% vs. 1/32-nuclei: 47%, 25% and 19%; P > 0.05), respectively. In embryo transfer assays, both 1/32-reconstructed zygotes and control, non-manipulated zygotes were transferred to synchronized does Four live reconstructed fetuses (4/49: 8 1% survival rate) and five in regression stage (9/49: 18% implantation rate) were observed on Day 21 post-ovulation, whereas from control zygotes, 11 fetuses were alive (11/53 21% fetal survival rate) and 2 degenerated (13/53 x 24 5% implantation rate). Similar results were obtained from a final experiment, in which development was allowed to progress to term. Six live rabbit pups derived front experimentally reconstructed zygotes (11%; 6/54) and three fetuses in regression stage were obtained; values slightly lower than those derived from non-manipulated and transferred control zygotes (18% 9/50, live born rate).

[http://www.ncbi.nlm.nih.gov/pubmed/11589623?ordinalpos=412&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum]
Effects of leukaemia inhibitory factor on endometrial receptivity and its hormonal regulation in rabbits.Liu CQ, Yuan Y, Wang ZX.
Shanghai Institute of Planned Parenthood Research, Shanghai, P. R. China.

The effects of hormones on production of leukaemia inhibitory factor (LIF) and the uterine receptivity in rabbits were studied. In ovariectomised rabbits, LIF protein was not detected in control but upregulated by progesterone alone. Oestrogen had a slightly negative effect when the rabbits were treated with both oestrogen and progesterone. Mifepristone (Mi) inhibited the progesterone-stimulated production of LIF in rabbit uterus. The transfer of embryos to LIF-treated recipients significantly increased pregnancy rate (70%) and implantation rate (27%) as compared with control (pregnancy rate=40% and implantation rate=17%). The transfer of embryos to LIF and mifepristone-treated recipients significantly decreased pregnancy rate (30%) and implantation rate (9%). The results indicated that LIF protein had a beneficial effect on uterine receptivity and mifepristone prevented this effect. Copyright 2001 Academic Press.

[http://www.ncbi.nlm.nih.gov/pubmed/8447943]
Effects of strain and embryo transfer model (embryos from one versus two donor does/recipient) on results of cryopreservation in rabbit.Vicente JS, García-Ximénez F.
Departamento de Ciencia Animal, Universidad Politécnica de Valencia, Spain.

Differential effects of 2 transfer models for normal thawed embryos of 1 donor doe were studied on the offspring rate and their embryo survival at birth from 3 selected rabbit strains (SY and SB: synthetic strains, NZ: New Zealand White). Morulae were obtained 64-66 h post-coitum from 93 adult does treated with 25 IU of hCG (SY:36, NZ:27, SB:30). Morphologically normal morulae were frozen in the presence of 1.5M DMSO and stored in liquid nitrogen. Normal thawed embryos were transferred into the oviducts of synchronized recipient does of the same strain 48 h after being injected with 25 IU of hCG (SY:28, NZ:21, SB:24). Each recipient received embryos from 1 (single transfer) or 2 different donor does (double transfer). Significant differences were observed in the post-thawing percentage of normal embryos between strains (SY:95 +/- 1% and SB:85 +/- 3%, P < 0.05; NZ: ,91 +/- 2%). After transfer, no significant differences were observed in pregnancy rate and offspring rate between the transfer models, whereas significant differences were only found in survival rate when all transfers were analyzed (double: 24 +/- 4% vs single: 14 +/- 3%, P < 0.05). An effect of strain was detected in the pregnancy rate (NZ: 33% vs SB: 71%, P < 0.05; SY: 61%) and in the survival rate per donor doe on pregnant recipient doe (SY: 42 +/- 5 vs SB: 19 +/- 5, P < 0.05; NZ: 34 +/- 7%). These results suggest a differential embryo sensitivity with respect to their genetic origin in both the freezing-thawing and transfer procedures.

[http://www.ncbi.nlm.nih.gov/pubmed/14564113]
'''Developmental stages in the rabbit embryo: guidelines to choose an appropriate experimental model.'''Beaudoin S, Barbet P, Bargy F.
Department of Pediatric Surgery, Groupe Hospitalier Cochin-Saint-Vincent de Paul, Paris, France. sylvie.beaudoine@svp.ap-hop-paris.fr

Researchers involved in the field of congenital malformations are often forced to work on an animal model. Both accurate description of its normal development and comparative staging with human development will be mandatory. To complete the lacking medical literature, we herein provide such data for the rabbit model. Sampled rabbit embryos were staged using the Carnegie criteria, in order first to determine if they were consistent with the rabbit developmental pattern, and second to compare this pattern with the human one. Our results show a suitable comparison of rabbits and humans in early developmental stages, except for the neural growth. Copyright 2003 S. Karger AG, Basel

Talk:2009 Group Project 1

2009-10-14T12:39:38Z

Z3185685: /* Actual Changes Made */

== Lab 10 ==
--[[User:Z3283499|Antonio Lee]] 10:52, 2 October 2009 (EST) Hi everyone, I will be working with you during the Lab10 Tutorial and here is the news link and PDF of the manuscript for your group exercise. I encourage you to read the paper before the tutorial. Also, please indicate next to the questions below (using either your initials or student number) which one of the four questions you wish to address.
:'''Group 1 :''' [http://www.nature.com/nature/journal/v461/n7262/full/461354a.html '''Developmental biology: Asexual healing'''] in Nature News and Views - Nature 461, 354-355 (17 September 2009) [[Media:ANAT2341_Lab10_2009_Group 1 Reading.pdf|Manuscript (PDF): Mitochondrial gene replacement in primate offspring and embryonic stem cells]]

:Question 1. What is the background to the existing problem / disease condition? --[[User:Z3187802|Vishnnu Shanmugam]] 22:12, 2 October 2009 (EST)

Mitochondria are found in all eukaryotic cells and contain their own genome (mitochondrial DNA or mtDNA). Unlike the nuclear genome, which is derived from both the egg and sperm at fertilization, the mtDNA in the embryo is derived almost exclusively from the egg; it is of maternal origin.

Mutations in mitochondrial DNA (mtDNA) can lead to a range of chronic incurable diseases such as myopathies, neurodegenerative diseases, diabetes, cancer and infertility. Mutations in mitochondrial DNA could also contribute to other diseases such as Alzheimer’s,
Parkinson’s and Huntington’s diseases

A normal cell should be homoplasmic in its mitochondrial DNA, that is it should only contain one type of mitochondrial DNA. But if the cell has two or more types of mitochondrial DNA (a mixture of normal and mutated DNA) it is known as heteroplasmic and can lead to a range of diseases. These genetic mutations can also be passed to offspring causing disease.
1 in 3,500–6,000 are at risk or presently have a disorder from mutations in mitochondrial DNA. Disease progresses slowly and there are no cure. Limitations in assessing the extent heteroplasmy and accuracy in calculating the risks of developing mtDNA related disease means that a new approach is needed to tackle the problem.

:Question 2. What approach / method did the research team take to tackle / improve the problem?--[[User:Z3126328|Jin Lee]] 12:31, 7 October 2009 (EST)
:Working with rhesus macaque monkeys, the authors reconstructed mature oocytes containing the nuclear genome from one oocyte and the mitochondrial genome from another. To do this they removed the nuclear genetic material from one oocyte, leaving behind all of the mitochondrial DNA, then transferred it to another oocyte whose nucleus had been removed (a cytoplast), but which contained a full complement of mitochondrial DNA.

:Question 3. What was the breakthrough / major advancement OR failure / drawback? and why might this be of significance?
::Drawbacks - --[[User:Z3186093|Jenny Guy]] 22:43, 7 October 2009 (EST)
:::There were difficulties in visualising and isolating the intact chromosomes, as well as the mtDNA being susceptible to damage and translocation/movement. Visualization became easier after the development of techniques for DNA staining with fluorophores and looking under UV light during embryo cloning by the SCNT (somatic cell nuclear transfer). Successful implementation to avoid damage to the cytoplast during spindle removal involved using polarized microscopy. (p368) --[[User:Z3186093|Jenny Guy]] 14:12, 8 October 2009 (EST)
:Question 4. What are the next steps in moving forward? What are the next or new hurdles to overcome?

==Actual Changes Made==

'''Concise Version:''' (Everyone add their changes here)
# Removed cleft palate and cleft lip section (Abnormal development) --[[User:Z3187802|Vishnnu Shanmugam]]
# Altered references (current research and abnormal development) --[[User:Z3187802|Vishnnu Shanmugam]]
# Added picture guide for transgenic rabbit --[[User:Z3187802|Vishnnu Shanmugam]]
# Added picture guide for rabbit cloning --[[User:Z3187802|Vishnnu Shanmugam]]
# Removed newspaper image of rabbit (Current research) --[[User:Z3187802|Vishnnu Shanmugam]]
# Formatted pictures and text to reduce gaps in the assignment (current research and abnormal development) --[[User:Z3187802|Vishnnu Shanmugam]]
# Corrected spelling mistakes in images (current research and abnormal development) --[[User:Z3187802|Vishnnu Shanmugam]]
# Reviewed all images and have written a summary, original source, copyright information (current research and abnormal development) --[[User:Z3187802|Vishnnu Shanmugam]]
# Formatted the look of the genetics section, including 'abnormalities' --[[User:Z3186093|Jenny Guy]] 16:31, 14 October 2009 (EST)
# Fiddled with position of images in genetics section --[[User:Z3186093|Jenny Guy]] 16:31, 14 October 2009 (EST)
# Fixed spelling mistake in History - Jin Lee
# Added images in table of stages. --[[User:Z3185685|Sumaiya Rahman]]
# Added to introduction and related it to the rest of the page. --[[User:Z3185685|Sumaiya Rahman]]
# Scale added to diagram of relative sizes of rabbit embryo

'''Long Version:'''

--[[User:Z3187802|Vishnnu Shanmugam]] 23:46, 10 October 2009 (EST) Okies, all done. I'm going to review all my images and add summaries to them. Dr. Hill asked for a concise version to all the changes we make from the peer review process. I suggest everyone add their changes to the list I have started above and place your signature next to it.

--[[User:Z3186093|Jenny Guy]] 14:29, 10 October 2009 (EST)Hey vishnuu, i was thinking could you please alter
* the gaps between the spina bifida images (format this somehow with the images on the side and text on the other)
* the gap under "Brachydactylia & Acheiropodia"...maybe you have entered down too much????
cheers :)

--[[User:Z3187802|Vishnnu Shanmugam]] 21:27, 9 October 2009 (EST)Hey all. I have removed the newspaper image of rabbit (Due to copyright issues), and have replaced it with a series of images that guides the reader through the process of cloning a rabbit. I have NOT altered the text summarizing the creation of transgenic and clone rabbits as there are very important & detailed information which if removed puts complex processes in danger of oversimplification. I also corrected spelling mistakes in some images.

--[[User:Z3187802|Vishnnu Shanmugam]] 20:22, 7 October 2009 (EST) Hey gang. By popular demand (or the stress of reading) people want less text. I have removed the entire cleft palate & cleft lip section from abnormal development. For current research, I have also created a step by step picture guide for transgenic rabbit creation. It was initially meant to be a video, but this wiki page does not display (.gif) or (.mov) files. Sum, I remember that you did your references after me...so when I removed the cleft palate & cleft lip section, the references changed....so I have also adjusted your references accordingly. I don't think it is necessary to make all the changes outlined below as most comments are subjective (different people have different preferences) and seems like some comments were made because people had nothing else to propose.

--[[User:Z3126328|Jin Lee]] 10:01, 8 October 2009 (EST)Hi Guys, I have fixed spelling mistake and some people commented to make table form for advantages and disvantages section. But I liked the way I presented so I will leave in point form.

--[[User:Z3186093|Jenny Guy]] 14:32, 8 October 2009 (EST)
Hey! I looked at what i could change in the genetics section and decided to format a little. Our peers asked:
* genome information into a table - this is a little silly since there'd only be one column.
* Reformating in sections such as hitory and genetics. - have tried to do a little.
* Make pictures appear on the same side of page. maybe aligning the pics on either the left or right side instead of both left and right, and possibly putting them as thumbnails could also work. - i tried to put both of the chromosome images ont he same side (tried both left and right) but found that it looked terrible considering the size (which is needed to see it) as the text wouldnt fit around it very well.
* it will look much better if there is some work to be done for the structure of it especially the paragraph under the heading of 'abnormalities'. - am still in the process. not sure what else i can do since its in basic dot point form with not a large text to format. any ideas? or shall i leave it how it is now?
* maybe instead of writing the entire reference, you could just state The Broad Institute or just the people related to it - i feel that the entire team needs a mention since all people relate to it. noting just the broad institute is almost like noting a team of people here in unsw as just plainly "UNSW" which is just disrespectful.

==Things to work on noted by peers==

Hey, So the changes i will make will be in the introduction section. Also a lot of people have said to add pictures in the stages section to make it more interesting. I couldnt get permission to use the images so i bought tracing paper today! lol will try to draw them and see if they are ok enough to add. I think i am going to leave the timeline section as is because most people liked it. What do u guys think? --[[User:Z3185685|Sumaiya Rahman]] 15:31, 8 October 2009 (EST)

Sounds great Sum....Its gonna take some effort to trace it then scan it. GL --[[User:Z3187802|Vishnnu Shanmugam]] 21:37, 9 October 2009 (EST)

Hey guys,
I read through all the notes our peers have given us and summarised them into the following sections. Majority of them overlap (where ive put a new persons opinions in the same dot point over and over to stress the point on how many people noticed). Some things are easily changed, most of all i reckon its
# formatting
# pictures
# text to be more concise
So we just need to finalise all these minor things to improve our project. Please detail any changes you've made in the the heading above.
Cheers, --[[User:Z3186093|Jenny Guy]] 20:30, 7 October 2009 (EST)

INTRODUCTION
* a little too brief, more information needed
* For the first sentence (the characteristics that make the rabbit an excellent model for study), mention the section 'Why are we using rabbits?' under History section.
* For the second sentence (study that developed and improved micromanipulation techniques), mention the 'Transgenic Rabbit' section below under the genetics section. I've read the entire project page, and the introduction was the only place I found that was not precise enough (which is a great thing). These are minor things, but I think they will help with improving your project page.
*suggestion: Place the history section after the Introduction. This gives the viewer an overview of the use of the rabbit embryo. This way the viewer is first subjected to a few examples of the rabbit embryos use. It also allows him/her to understand where the rabbit embryo sits in with history. I guess this is a matter of personal preference.

HISTORY
* The advantages and Disadvantages would be better in a table. the history you might want to put the advantages and disadvantages into a table to make the page look a bit more tidy and easier to read when we go through it.
* The usage of rabbits for experimental models in science and medicine could be stated under the history section to allow background information for the readers to become aware of the topic and why the rabbit have been used to study specfic medical procedures and diseases.
* Spelling mistake under 'Discovery of Graafian Follicle', 2nd paragraph. I think it's previous instead of 'previcous'.
* Reformating in sections such as hitory and genetics. Make pictures appear on the same side of page.
* The history section can be improved if the infomation is expanded to give some more detailed background knowledge although i like the idea that the information is concise describing each scientists contribution towards the model.
* could be formatted to make the information stand out and a lot more appealing, I would recommend including pictures if possible that link to the text and making the advantages and disadvantages into a table rather than listing it.

TIMELINE
* more images to wholly understand. timeline/staging section was clear and concise, however it could be improved by adding more colour/pictures to maintain the readers' interest. The timeline and staging bits are very well written and clear but i think you should add a few images in there to match up with the text. Perhaps some pictures of embryos throughout development. Pictures for every stage would make it more visually attractive rather than just reading text. lack of pics in the timeline.
* It’s a little confusing that the development jumps back and forth according to the body part developing. Maybe it should be categorised according to time of development instead for greater clarity at first glance
* The timeline is just a little confusing, as its divided into development of different parts, which breaks the time flow.
* some of the information for the timeline section was too heavy for the page - would recommend only using some of the information on your actual page and having the rest as links to separate pages

STAGING
* pictures for stages would have been nice, unless there were none????
* a more even distribution of information, particularly more detail in the stages
* Provide pictures for individual stages. Get visual, and make the stages interesting to read. include pictures in the stages section.
* Staging section is also very well presented but the information presented in a table would even look better if there is use of some pictures to make it more interesting for its audience.
* staging section was very bland and would be more appealing with pictures. I dont think its necessary to cite your entire reference within the text

GENETICS
* genome information into a table
* Reformating in sections such as hitory and genetics.
* Make pictures appear on the same side of page. maybe aligning the pics on either the left or right side instead of both left and right, and possibly putting them as thumbnails could also work.
* it will look much better if there is some work to be done for the structure of it especially the paragraph under the heading of 'abnormalities'.
* maybe instead of writing the entire reference, you could just state The Broad Institute or just the people related to it

ABNORMAL DEVELOPMENT
* There is also a lot of content which might be alleviated by reducing the section on abnormal development. Too much information about the abnormalities. make more concise.
* the abnormalities went a bit over board, and didn't need that much attention I think (as compared witht the research which was good)
* reduce the writing content. for example. In the current research section, you have two scientific process of transgenic rabbits as well as cloning which is described in how these are done. why not draw a step by step diagram, and put these written steps in the link to the image.
* The information provided under Hydrocephalus and Brachydactylia was informative and interesting, but it contained too much text. I suggest you narrow it down and make use of Dots point, numbering, bold/italic words, and/or sub-sub-headings.
* Section for "Abnormal Development" gives the readers useful amount of information but i think its very lenghty, use of dot points can make it look even better and easy to understand.

CURRENT RESEARCH
* the group makes good usage of diagrams but towards the end diagrams die out, you might want to make the current research part of your assignment into diagrams and steps as there is just a bunch of information thrown there and alot of reading needed, if you put it into steps or diagrams it will make the marking process and reading process easier and allow us as reader to understand the information with ease.
* 'Transgenic Rabbit' should be shifted toward the genetic information on the rabbit. (Jenny - i dont agree with this as its research, not its offical genetics. Vishnnu - Neither do I)
* information in regard to stem cells should be brief and truncated. Example in regard to stem cell research should have brief and simple model explaining the process and why it used.
* There is too much information under stem cells. There is 2 examples of studies dealing with stem cells. A suggestion would be to just have one, and have a link saying 'Koga's research on Stem Cells'.
* Have the section 'links to Research labs and researchers' placed at the end of current research. That way, the information on the page will flow smoother.
* more of a focus on current research i.e. what each method is being used for and less on the process behind each method.
* great amount of information but in my perspective replacing the paragraphs with some dot points with heading and subheadings would further enrich understanding of readers.

OVERALL
* "As you start going down the page though the information starts to read a bit haphazardly, for example the developing body; jumping for section to section and the timeline section. it would be great if you could clean this up as it doesn't really flow." - formatting
* condense long slabs of text as the page is long
* format it so there are no huge gaps
* move the links to current research labs up closer to the current research section, just to keep it all together

==Constructive Criticism of Coordinator==
--[[User:S8600021|Mark Hill]] 08:07, 8 October 2009 (EST) The following comments are general in nature in no specific order, as it would be inappropriate to suggest specific changes and then assess the final project. Comments will be added during this week and you still have one week before final submission.

* There is no concise list of changes made to your project on the basis of peer assessments.
* Timeline of Embryo Development early stages, are in the introductory text said to be in hours, but it would be good to see it in the list as well.
* [[:File:Sizes.JPG]] Relative sizes, but no absolute size or scale given.
* A general comment about images. When you click an image and it opens, the information below the image should have an explanation of what the image shows, a reference (if from a paper) and a link to the original source (if available) as well as copyright information.
* Did you actually read the terms of use for this image that you cut n pated into the image description? [[:File:Rabbit_hybrid.jpg]] "For this purpose alone you may retrieve and display the Content on a computer screen. You may also print out, but not photocopy, one copy of individual files on paper and store files in electronic form on disc, but not on any server or any other storage device connected to a network where the Content could be accessed by other users." It clearly states that you cannot use this image online.
* Chromosomes section, images have no legends and structure not clearly organised.
* There needs to be better checking of your spelling and grammar, for example [[:File:Rabbitmalformation3.jpg]] "Plant Patkology of Tke Rockefeller Institute for Medical Researck", these mistakes while not major, suggests a lack of reviewing of your work by the group.
* Just a comment on project "feel", when several people work together on a project and insert their parts, the final project sometimes has an uneven style. Now that you have time to tidy up, try and get a common appearance throughout your project.

==Constructive Criticism of Peers==

--[[User:Z3218657|Sally Clarke]] 09:32, 1 October 2009 (EST)
Nice work Guys!
- Fantastic images used throughout - maybe a few more in the timeline so we can understand what is going on
- As you start going down the page though the information starts to read a bit haphazardly, for example the developing body; jumping for section to section and the timeline section. it would be great if you could clean this up as it doesn't really flow.
- The section on the abnormal development is great.
- The page is quite long - Maybe you could condense some of the text as it is kind of slab like
- i really enjoyed the breeding section
- The advantages and Disadvantages would be better in a table.

--[[User:Z3223194|Bronwyn Lewis-Jones]] 08:08, 1 October 2009 (EST) Hi Group 1! This is obviously a well organised and well researched assignment. I found it very informative. There are (of course) some things I feel could improve the overall submission. I loved that the timeline/staging section was clear and concise, however I think it could be improved by adding more colour/pictures to maintain the readers' interest. There is also a lot of content which might be alleviated by reducing the section on abnormal development. Hope this helps :)

--[[User:Z3218146|Julianna Lam]] 01:11, 1 October 2009 (EST) good job guys.
-Theres alot of relevant information.
-The timeline and staging bits are very well written and clear but i think you should add a few images in there to match up with the text.
-The image for the genetics bit is awesome.
-The page is nicely set out.
-Too much information about the abnormalities.

--[[User:Z3258567|Sando Rashed]] 20:04, 30 September 2009 (EST)hey guys, your page looks good, starts off well as there is not a bunch of information just thrown in, the information used is well thought, with the history you might want to put the advantages and disadvantages into a table to make the page look a bit more tidy and easier to read when we go through it (you can also do this with the info under genome), the group makes good usage of diagrams but towards the end diagrams die out, you might want to make the current research part of your assignment into diagrams and steps as there is just a bunch of information thrown there and alot of reading needed, if you put it into steps or diagrams it will make the marking process and reading process easier and allow us as reader to understand the information with ease, other than that the page looks quite good, well done on all your contributions

--[[User:Z3218792|Gabriela Pinget]] 21:51, 29 September 2009 (EST)

Nice page. I particularly liked the idea of lists of what is to come before each flood of information as was done with the ‘history of model use’ section.

- Nice easing into the topic with ‘advantages’ and ‘disadvantages’ lists.

- I liked the of rabbit embryo development to that of humans- puts it into perspective

- Good glossary- informative but not over- the- top

- Nice genetics section! Easy to read and a great use of illustrations to break up the information

- I also like that you took a page out of Mark’s book in the addition of the abnormalities section

Improvements:

- Perhaps some pictures of embryos throughout development.

- It’s a little confusing that the development jumps back and forth according to the body part developing. Maybe it should be categorised according to time of development instead for greater clarity at first glance

--[[User:Z3295026|Joe Nassif]] 17:01, 29 September 2009 (EST)

Your assessment has come along great in regard to the criteria format. There are a few alterations that could improve your project, the following alterations may enhance your wiki page:

'''-''' The usage of rabbits for experimental models in both science and medicine could be state under the history section to allow background information for the readers to become aware of the topic and why the rabbit have been used to study specfic medical procedures and diseases.

'''-''' Secondly the information on 'Transgenic Rabbit' should be shifted toward the genetic information on the rabbit. So far the project is looking and coming along great except for minor edits.

'''-''' Background information should be placed subsequent to the introduction allowing the reader to understand why this specific animal is used for specfic purposes.

'''-''' Figures/Graphs and the illustration of the anatomy and genetic development of the embryo were useful and clear allowing the viwers to understand and learn through the demonstration of pictures which were extremely informative.

'''-''' Genetics: the Genetics and Abnormalities information was great and very informative. It was great how the group compared the embryo with the human chromosome allowing the audience to understand the difference between both.

'''-''' Abnormalities: Information and details which were in the genetic section provided informative and interesting information, and it could be truncated a bit, additionally just discussing the chromosome development of the rabbit.

'''-''' Current Embryology Research: information in regard to stem cells should be brief and truncated. Example in regard to stem cell research should have brief and simple model explaining the process and why it used.

'''-''' Consequently, I thought the project was good it flowed and was very informative. The information was detailed, and the illustrations were useful and allowed the readers to gain a brief overview on the topic and it usage in history and in current research. Overall group 1 seem to achieve the critriea outcomes and summarised the topic really well, the comparsion to human embryo development througout the text was great and is a good referencing point in comparsion to the species choosen.
Great job --[[User:Z3295026|Joe Nassif]] 17:01, 29 September 2009 (EST)

--[[User:Z3255007|Sadaf Masood]] 12:09, 30 September 2009 (EST)Hello Group 1! Congrats on your awesome group project! I must say im very impressed with all the information you have posted and i have listed down the good bits and the bits that need to be improved. Since i am posting this a lil late, i have seen that u have already improved your project and few aspects...Good Job guys!

1. Very brief introduction...maybe just a little bit more info will be perfect

2. Abnormalities section is very informative and well researched, but very long, how about making it a little more precise?

3. The Advantages and Disadvantages of the using Rabbit is just simply perfect

4. The timeline is just a little confusing, as its divided into development of different parts, which breaks the time flow.

5. Pictures for every stage would make it more visually attractive rather than just reading text

6. Great Glossary!

There were few things earlier that need to be improved but you guys fixed it as soon as comments were posted so basically you guys rock :)An excellent effort guys. Best Wishes

# --[[User:Z3217015|Mitchell Mathieson]] 09:45, 25 September 2009 (EST)Very nice. The information was maybe a bit spread out, with heaps of gaps everywhere (formatting???), but the information was there, and relevant, and easy to read. I like how there was tonnes of information on current research, as I think that was the main aim, but the abnormalities went a bit over board, and didn't need that much attention I think. pictures for stages would have been nice, unless there were none???? The references are top notch, and the glossary is pretty amazing, and in the right place. Overall very good, I think formatting was the major downfall though, as it makes the page that much longer, and hence a little bit more difficult to read.

--[[User:Z3224449|Elide Newton]] 14:12, 26 September 2009 (EST)
HEllO GROUP 1: Well done on such a great assignemnt, looks like you have all worked very hard. Well my one point of constructive criticism would be to reduce the writing content. for example. In the current research section, you have two scientific process of transgenic rabbits as well as cloning which is described in how these are done. why not draw a step by step diagram, and put these written steps in the link to the image. that way it is more visual, the info is still there under the image link, and the page wont look as daunting to read. :) hope this helps!

--[[User:Z3254857|Begum Sonmez]] 00:46, 26 September 2009 (EST)
Hello Group 1. Firstly, I would like to let you all know that you have all done a great job. I'm impressed. I have a few suggestions that I think mite help to improve the page even more:

*Introduction:

1)For the first sentence (the characteristics that make the rabbit an excellent model for study), mention the section 'Why are we using rabbits?' under History section.

2)For the second sentence (study that developed and improved micromanipulation techniques), mention the 'Transgenic Rabbit' section below under the genetics section. I've read the entire project page, and the introduction was the only place I found that was not precise enough (which is a great thing). These are minor things, but I think they will help with improving your project page.

3)Breeding information was informative.

4) A suggestion: Place the history section after the Introduction. This gives the viewer an overview of the use of the rabbit embryo. This way the viewer is first subjected to a few examples of the rabbit embryos use. It also allows him/her to understand where the rabbit embryo sits in with history. I guess this is a matter of personal preference.

*Timeline:

1)Graphs, and the illustration of the zona pellucida and mucin coat were very clear and informative.

*Staging: I had no problems with it. The lack of information I think was a plus. It touched on the content in the Timeline section.

*History:

1) I loved the idea of the 'Disadvantages' of the rabbit embryo, it seemed unbiased. The brief timeline provided a clear and short summary.

2) Spelling mistake under 'Discovery of Graafian Follicle', 2nd paragraph. I think it's previous instead of 'previcous'. Also, the 2nd paragraph under this heading does not flow that well. Try rephrasing the 2nd sentence.

*Genetics:

The Genetics and Abnormalities section flow into eachother very well. I appreciated the comparison of the rabbit chromosome to the human chromosome.

*Abnormalities:

1) The information provided under Hydrocephalus and Brachydactylia was informative and interesting, but it contained too much text. I suggest you narrow it down and make use of Dots point, numbering, bold/italic words, and/or sub-sub-headings.

*Current Embryology Research:
1) There is too much information under stem cells. There is 2 examples of studies dealing with stem cells. A suggestion would be to just have one, and have a link saying 'Koga's research on Stem Cells'.

2) Have the section 'links to Research labs and researchers' placed at the end of current research. That way, the information on the page will flow smoother.

Overall, I thought there was a consistent structure in each section. The information was informative, and the pictures were relevant and helped me better understand the topics of discussion.

--[[User:Z3252340|Emily Wong]] 10:58, 27 September 2009 (EST) Firstly, great work. It is a well researched, structured and organised page. The content is very in depth and includes information on all of the specified areas. It is well referenced, with an extensive reference list indicating the amount of research put into the page. Some areas are more detailed than others. For example, the staging section is quite short and concise where as the Abnormal development section is extremely long considering it is not a needed topic. There is moderate use of pictures and diagrams, but more use could benefit the page as it may be able to negate some of the large slabs of text. The comparisons made between the human and the rabbit embryos are a good part of the project page. Each member of the group has contributed to the page and provided a lot of information on the section of content they were working on. What would improve this project is a more even distribution of information, particularly more detail in the stages, a few more diagrams or pictures to negate some of the text presented, more of a focus on current research i.e. what each method is being used for and less on the process behind each method.

--[[User:Z3126345|Gang Liu]] 14:26, 27 September 2009 (EST)In my opionion, this is a well constructed page. It includes major subheadings such as history, timeline, stages, genetics and current research. It is very concise and straightforward, which makes it easy to read. For example, a short introduction paragraph,"...the rabbit is an appropriate animal model as the results from many experiments are significant to that of other mammals, including humans.", explains to reader why rabbit is such a suitable model.

It also provides a logic flow. For example, in history of rabbit model use section, it has provided advangtages and disadvantages of model use. This is appropriate, as it demonstrates the significance of rabbit model use in scitific discovery. In addition, it has provided detailed background information for each discovery. This makes it interesting to read.

It is also important to compare development of embryo between rabbit and human. For example, "... the similarities of this developmental pattern in humans and rabbits, suggests that the same growth increment is required to achieve the same stage. The main difference observed between human rabbit gestational duration is due to the fetal growth phase...", this has suggested human and rabbit share many similarities. Not only this page has demonstrated detailed written information of timeline development, it also provided graphics to reinforce the concept. For example, the hand drawing of developing embryo. As well as the comparison between human embryo and rabbit embryo timeline development.

It is also interesting to learn that rabbits have 22 pairs of chromosome, whereas humans have 23 pairs of chromosome.

Sections such as abnormal development and current research have demonstrated extended research and understanding. For example, hydrocephalus, spina Bifida, stem cell research and cloning techniques. All of these have showed the in depth research in textbooks, journals and internet based literatures.

However, this page can be improved by considering the following points.

*Provide pictures for individual stages. Get visual, and make the stages interesting to read.

*Reformating in sections such as hitory and genetics. Make pictures appear on the same side of page.

*Typo: "A rabbits potential for reproduction..."

*Sections such as abnormal development and current research are too lengthy. Might consider shrink the content.

*Lack of glossary.

Overall, big thumbs up!

--[[User:Z3252231|Angama Yaquobi]] 01:12, 28 September 2009 (EST)
First of all i would like to congratulate all the team members for a great team work.
Well done guys!! The group project looks amazing, the information presented is very concise
and straight to the point which makes it very easy for the readers to grab
the important information that they need to enhance their knowledge.
I like the section of history, the information is very clear,
and i like the idea of providing some background knowledge to the readers
about the disadvantages of the use of rabbit.
The history section can be improved if the infomation is expanded
to give some more detailed background knowledge althought
i like the idea that the information is concise describing each
scientists contribution towards the model.
The section for timeline is impressive, in my perspective its a great idea to cover alot of content in a very smart way
which is by the use of subheadings to make it easy to understand for audience.
Staging section is also very well presented but the information presented
in a table would even look better if there is use of some pictures
to make it more interesting for its audience. Genetics section
is beautifully presented, all the information is there with some
amazing pictures but will look much better if there is some work to
be done for the structure of it especially the paragraph under the
heading of 'abnormalities'. Section for "Abnormal Development" gives
the readers useful amount of information but i think its very lenghty,
use of dot points can make it look even better and easy to understand.
The same for Current embryology research, great amount of information but
in my perspective replacing the paragraphs with some dot points with
heading and subheadings would further enrich understanding of readers.
Also glossary would complement the webpage. But overall,
great amount of information which shows alot of research
which has been done by all the team members. Well done guys!!

--[[User:Z3217686|Thomas Dangerfield]] 13:29, 28 September 2009 (EST) Hey guys! Good work on your assignment! Plenty of info which is good, and very well referenced. The glossary is a good idea too! I do agree with a few others about the lots of clear spaces in the formatting, and the lack of pics in the timeline though. Also under the genetics section, maybe aligning the pics on either the left or right side instead of both left and right, and possibly putting them as thumbnails could also work. In the abnormalities section, there might have been a little too much info that probably wasn't needed, but i do like the effort put in. Over all, possibly more time spent on formatting and determining which sections are more important and which sections may need to be limited. Other than those points, the whole assignment seemed very well done!

--[[User:Z3215682|Carly Mooney]] 11:32, 29 September 2009 (EST)
You assignment is visually appealing and the genetic information e.g. the number of chromosomes of a rabbit was very interesting.There are some additional sections you have added which really complement your assignment e.g the abnormalities and I really liked the advantages and disadvantages of using the rabbit model. The few suggestions I would make is to:
* include pictures in the stages section
*place the pictures throughout the text (e.g. to left or right). You did this up until abnormalities and I felt it broke the flow of the written text.
* and maybe move the links to current research labs up closer to the current research section, just to keep it all together.
Overall very impressive though.

--[[User:Z3220040|Joanne Raffel]] 15:25, 29 September 2009 (EST) Nice wikipage, the page looked interesting however I agree with some others that the formatting of the page was inconsistent. I thought the referencing was great but found it a bit confusing with the reference numbers after the paragraphs. I thought the subheadings werent distinct enough, especially in relation to the text, which made it difficult to read. The history section could be formatted to make the information stand out and a lot more appealing, I would recommend including pictures if possible that link to the text and making the advantages and disadvantages into a table rather than listing it. I especially liked the comparison between the rabbit and the human embryo, however some of the information for the timeline section was too heavy for the page, I would recommend only using some of the information on your actual page and having the rest as links to separate pages. The staging section was very bland and would be more appealing with pictures. I dont think its necessary to cite your entire reference within the text, especially in the genetics section, maybe instead of writing the entire reference, you could just state The Broad Institute or just the people related to it. The abnormalities section was a good inclusion however it was very extensive, along with the current research section. Overall a very good wikipage.

----
*Hey, Well done guys!!! I think our group worked pretty well! I think we communicated each other well and did very best for their section. I fixed my spelling mistake and problem with sentence! As Begum mentioned, I think placing the history part after the introduction is better idea. --[[User:Z3126328|Jin Lee]] 13:36, 26 September 2009 (EST)

*Hey guys,
the project has come together brilliantly! it looks quite good. Hopefully mark will like it! ill add some terms to the glossary and try do some formatting (the first image is a little too big i think!) --[[User:Z3186093|Jenny Guy]] 10:28, 24 September 2009 (EST)

Hey. Yep all good. I had to get rid of the pics, so stages table is now blank. Im pretty much done. I'll see what i can add to the glossary. thanks :)--[[User:Z3185685|Sumaiya Rahman]] 23:34, 23 September 2009 (EST)

Hey all, I'm going to start a glossary and add it under the reference section. Scan your text and add to the glossary in alphabetical order. Also under the marking criteria, it says to provide links to researchers and research laboratories.....i'll start that under the glossary. Everyone else OK with their stuff?--[[User:Z3187802|Vishnnu Shanmugam]] 23:08, 23 September 2009 (EST)

Hey Sum, The images look fine but I don't think you can use the images like that since the journal KARGER is being particular about its copyright laws. I tried tracing around the images but it does not seem to resemble anything like an embryo. I did however find this link...go to it and scroll down to the images of the developing embryo. You might be able to edit it to resemble rabbit embryo. --[[User:Z3187802|Vishnnu Shanmugam]] 15:10, 23 September 2009 (EST). To get to the link, Google image search "rabbit gestation"....click on the "rabbit,gestation age" image from nature.com
Also google image search "The Haeckel embryo sequence"...could be useful after some editing

oh my god!! I summarised all of my research and wrote down on the page. Then I blew up everything!!!
it says 'edit conflict' what da?? I lost all of my work...it was my stupid mistake...--[[User:Z3126328|Jin Lee]] 01:06, 23 September 2009 (EST)

Oh also.. let me know if the images look stupid --[[User:Z3185685|Sumaiya Rahman]] 00:34, 23 September 2009 (EST)

Hey thanks vishnuu. I put some images up in the stages table. I did edit the pictures, but im not sure if im allowed to use it like this? have a look and let me know. Also im not sure what is going on with the reference section seems kinda all over the place, so i havnt added mine in yet. Maybe we should fix that up somehow? :) oh LOL about the breeding rabbits bit! haha
--[[User:Z3185685|Sumaiya Rahman]] 00:31, 23 September 2009 (EST)

Hey Sum, Sorry for the late reply. For $330, I'd rather breed rabbits and take the photos myself. I had a look at the original images, what we can do is trace around the developing rabbit embryo using the pencil tool on an image editing software(eg. microsoft paint - already preloaded into most windows). Then upload the image to the assignment. Does your PC have adobe fireworks?...extremely good for tracing images. If not, have a go at it with microsoft paint....I shall also have a go at it, then I shall let you know on this discussion page at about 3PM t'morrow. If any good then I'll send it to your student email. If not, we discuss potential alternatives. good luck Sum! --[[User:Z3187802|Vishnnu Shanmugam]] 23:51, 22 September 2009 (EST)

Yep thats the article i used for the developmental stages and put in a table. I should have my timeline posted by end of today. I also couldn't get permission to use the pictures as they wanted about $330 for me to use it!! no thanks. I'll see if i can work it in somehow. Vishnuu did u have any ideas on editing the images?? --[[User:Z3185685|Sumaiya Rahman]] 12:29, 22 September 2009 (EST)

Have a look at this article, it's helpful for comparison bt rabbit and human in developmental stages!--[[User:Z3126328|Jin Lee]] 13:35, 21 September 2009 (EST)
*Sampled rabbit embryos were staged using the Carnegie criteria, in order first to determine if they were consistent with the rabbit developmental pattern, and second to compare this pattern with the human one. Our results show a suitable '''comparison of rabbits and humans in early developmental stages''', except for the neural growth.
[http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowAbstract&ArtikelNr=73136&Ausgabe=229537&ProduktNr=224239
]

Absolutely correct Juliana, my research articles and their links are labelled 1-6 so far, the rest is yours..... I'll fix it for you. A timeline image seems tricky and i'm unsure, send Dr. Hill an email on m.hill@unsw.edu.au and see what he says. We still have till thursday to finish everything, so don't be too worried....try to finish all your other stuff and leave the drawing of the timeline last.--[[User:Z3187802|Vishnnu Shanmugam]] 17:49, 20 September 2009 (EST)

*no.1-7 in reference section is mine. and I think links under Vishnnu's research on the discussion board is mine. let me know please. (I can't remember all of my researches)
I want to make a timeline image but I can't do it;;; I asked Mark few weeks ago but havn't replied yet....can somebody help me???--[[User:Z3126328|Jin Lee]] 17:26, 20 September 2009 (EST)

'''** Hey Jenny, dont worry!! the project is not due until next week! (24th) we will have it done by then!! I am still waiting for permission to use the pictures in my stages section, thats why it hasnt been done yet. Hopefully i can get permission, otherwise i'll have to draw them (or something) myself.''' --[[User:Z3185685|Sumaiya Rahman]] 14:03, 17 September 2009 (EST)

It says project due date 24th september.......if the due date had been brought forward why was it not posted on the project main page? --[[User:Z3187802|Vishnnu Shanmugam]] 13:48, 17 September 2009 (EST)

EVERYONE...WHY IS THE REST OF OUR PROJECT NOT DONE??
* vishnuu...its due TODAY!! how can you post things up next Monday? Please make sure youve referenced EVERY image and all text (i know youve said you need to do this...but its easiest done when writing the section as now you have to go back and find everything, insert numbers etc. Remember to put the reference in the reference section. For the current research section i thought this might help you (as during my lecture in another class they spoke about how rabbits are used in heart development. Is there anything that you've found to include this?). Also I found this website during my research so it may help you? [http://www.evergen.com/rabbit_experience.html/ Rabbit Experiments]
* sum - where is the timeline???? It doesn't exist? Where is it? Also, we need some sort of visual for the staging. Have you found an images? Could you draw the stages of embryo development? It just looks incredibly boring.
* julianna...you need to put up more other than just two historians...there is NO referencing whatsoever in your entire section. where have you found this information? have you put it in your own words or copied it? You need to add some more refences to the reference section at the bottom..there just aren't many to back up your research.

seriously guys. ive added photos and tried to spice up the project but i am NOT going to finish your sections for you. ITS DUE IN 3 HRS! i cant believe you guys haven't bothered to even try finish this. Im very disappointed and i think its slack to let the team down. --[[User:Z3186093|Jenny Guy]] 10:34, 17 September 2009 (EST)

----

Hey all, just need to finish editing the current research part before i post it up, also need to edit some of my images under abnormal development and also references. Should be all done by Monday. --[[User:Z3187802|Vishnnu Shanmugam]] 07:02, 17 September 2009 (EST)

--[[User:S8600021|Mark Hill]] 01:40, 8 September 2009 (EST) OK guys, this is still just a page of text......

--[[User:Z3126328|Jin Lee]] 14:50, 3 September 2009 (EST) I want to make a timeline?

--[[User:S8600021|Mark Hill]] 08:42, 21 August 2009 (EST) z3187802 has contacted me and has been away sick. He should still complete his components of the group project.

Our group is Sum, Vishnnu, Juliana and Jenny. Today in the lab we have decided to research the RABBIT! [http://embryology.med.unsw.edu.au/OtherEmb/Rabbit.htm/ Rabbit embryology from Mark Hill]

(Juliana's email belebele85@msn.com)

----
This is apparently what we need to include in our case study:
#Timeline of Embryo Development - how long (SUM)
#Staging - are there species specific staging, what occurs when (SUM)
#History of Model Use - when was it first used, (JULIANNA)
#Genetics - chromosome number, sequencing (JENNY)
#Abnormal Development (VISHNNU)
#Current Embryology Research - research papers and findings (VISHNNU)

Hey guys, maybe we should add a section comparing rabbit to human development
--[[User:Z3185685|Sumaiya Rahman]] 16:45, 6 August 2009 (EST)

That sounds like a good idea Sum....seeing that human development is the primary theme of the course, not including it would be criminal!. -vishnnu

Report:
* Links to resources and discussions are to be posted on the group talk page, the project page is for the actual assignment
* Final assignment will be marked by another group and everyone will be given a marking criteria
* No information should be obtained from Wikipedia and all information (tables & graphs included) must be referenced
* Please feel free to suggest any further topics which can be included

== Research: ==
So i think the main rabbit used in research is the oryctolagus cuniculus. Lets focus mostly on that (or at least i, Jenny, will since im going genetics). This link is great for the specific genetics: [http://www.ncbi.nlm.nih.gov/nuccore/AJ001588/ Oryctolagus cuniculus complete mitochondrial genome]

Here's some stuff about benefits of modeling from a textbook. I haven't yet written as my own so its still the authors material. Just thought it might benefit us all (and raise our morale as we thought the rabbit might suck..but it doesn't!) We're not "submitting" this as our own work so technically we're not yet copyrighting their material.
Ive cited the book here and the website i got it from:
[http://books.google.com.au/books?id=RY0rXE2HgqsC&pg=PA344&lpg=PA344&dq=rabbit+embryology+genetics&source=bl&ots=rbr3CuBRxY&sig=p8055w9oYQmsQeuN78mgXBGmRK4&hl=en&ei=NI2KStaQJIvSsQOEpMjEDQ&sa=X&oi=book_result&ct=result&resnum=3#v=onepage&q=&f=false/ Cibelli, J., Lanza, R., Campbell, K. and West, M. 2002. Principles of Cloning. Academic Press]

“Rabbits were one of the first species in which blastomere nuclear transfer succeeded; as a model species, rabbits placed a central role in developing the micromanipulation technologies in embryos.” Other advantages for using rabbits are:

# “The costs to animal procurement, animal care, and oocyte production in rabbits are relatively low compared to large animals.” e.g. a cow embryo is 30x more expensive that a rabbit embryo
# “The developmental biology of rabbit embryos and fetuses resembles more closely that of large farm animals than that of rodent model species, including the transition from maternal to embryonic control of embryo development.”
# “The pregnancy of rabbits is relatively short (1 month), allowing rapid evaluation of fetal and postnatal development. In comparison, the gestation length for cattle is 9x longer.”
# “The sizeable milk production of rabbits allows their use as test animals for therapeutic protein expression in milk, or as a living bioreactor.”
# “Rabbits are induced ovulators. Domesticated rabbits are nonseasonal breeders and produce multiple offspring in one litter. These reproductive patterns make the use of rabbits for reproductive research highly efficient.”

----
Here are some links i (sum) found which may help. Need to go through all the info and sort it out, But there are a couple of good diagrams.

'''Links for group assignment'''

http://www.reproduction-online.org/cgi/reprint/48/1/43

http://books.google.com/books?id=RY0rXE2HgqsC&pg=PA344&dq=rabbit+embryo+stages&as_brr=3#v=onepage&q=rabbit%20embryo%20stages&f=false - good for what studies in rabbit embryo have been used for. And has a good table for embryological stages!!

http://books.google.com/books?id=ljAKtC-iIrIC&pg=PA264&dq=rabbit+embryo+stages&as_brr=3#v=onepage&q=rabbit%20embryo%20stages&f=false

http://books.google.com/books?id=73bbKzqRvLsC&pg=PA156&dq=rabbit+embryo+stages&lr=&as_brr=3#v=onepage&q=rabbit%20embryo%20stages&f=false - picture of implantation

http://books.google.com/books?id=aZ7DQYFyxswC&pg=PA122&dq=%22rabbit+development+stages%22&lr=&as_brr=3#v=onepage&q=&f=false
-------
Hi I(Juliana) uploaded file, you guys can have a look.
Go to 'Upload File' tab and click ' early growth of rabbit trophoblast' file.

-------------
also I found an interesting article!
'''An Electron Microscope Study of the Embryology of the Intercalated Disc in the Heart of the Rabbit'''
Alan R. Muir
The Journal of Biophysical and Biochemical Cytology, Vol. 3, No. 2 (Mar. 25, 1957), pp. 193-202
Published by: The Rockefeller University Press

http://info.library.unsw.edu.au/cgi-bin/local/access/ej-access.cgi?url=http://links.jstor.org/sici?origin=sfx%3Asfx&sici=0095-9901(1957)3%3A2%3C193%3AAEMSOT%3E2.0.CO%3B2-S
--

[[User:Z3126328|Jin Lee]] 10:48, 25 August 2009 (EST)

----------------
I found helpful book in the library
'''Bensley's Practical Anatomy of the Rabbit 8thE by E.Horne Craigie, Toronto, University of Toronto Press 1948'''
--[[User:Z3126328|Jin Lee]] 13:27, 27 August 2009 (EST)

==Vishnnu's Research==

'''Background reading (Vishnnu)'''

Hey everyone. I'm starting my background reading section where I shall describe my research resources. They contain a summary and a link to the resource itself. I shall keep this "notes" section updated with each new entry I add.

'''Notes:'''

*Articles 1 & 2 - Juliana this could be useful to you.

*Article 2 - Sum this could be useful to you.

*Articles 3 & 4 - Abnormal development articles (added: 02/09/2009)

*Articles 5 & 6 - Abnormal development articles (added: 13/09/2009)

'''Article 1'''

'''The rabbit as a model for reproductive and developmental toxicity studies''' --[[User:Z3187802|Vishnnu Shanmugam]] 21:05, 30 August 2009 (EST)

''Robert H. Foote and Edward W. Carney'' ''Reproductive Toxicology 14 (2000) 477–493'' ''Department of Animal Science, Cornell University, 204 Morrison Hall, Ithaca, New York 14853-4801, USA Developmental and Reproductive Toxicology, ''The Dow Chemical Company Midland, Michigan 48674, USA''

'''Summary'''

This is a review article of a study looking at the use of rabbits in toxicological studies. The article describes the advantages in using the rabbit experimental model as opposed to the rodent model (mice & rats) and outlines the differences that make toxicological studies on rabbit embryos more accurate than rodents to resemble similar toxicological effects in human embryos. The article describes various techniques that can be used (eg. blood collection from marginal ear vein, artificial insemination, embryo collection) and solutions to some common problems that researchers face when using animal models. Very interesting article with a great quote from Robert Koch to open the eyes of researchers to other animal models:

“Gentlemen, never forget that mice are not human beings”

Want to find out more? Follow the link!

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6TC0-41SBGDH-1&_user=37161&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_acct=C000004218&_version=1&_urlVersion=0&_userid=37161&md5=4db60dc9352996fc4865b9d781b0128d

'''Article 2'''

'''Developmental stages in the rabbit embryo: guidelines to choose an appropriate experimental model''' --[[User:Z3187802|Vishnnu Shanmugam]] 21:05, 30 August 2009 (EST)

''S. Beaudoin; P. Barbet; F. Bargy''
''Fetal Diagnosis and Therapy; Nov/Dec 2003; 18, 6; Academic Research Library''
''pg. 422''

'''Summary'''

The article describes the various stages in the developing rabbit embryo and the rationale for using rabbits to study normal and abnormal embryology. The article details normal developments in the rabbit embryo and compares it to the developing human embryo. By making this comparison the article argues for the validity of rabbit embryology to better understand human embryology and also suggests that due to the similarities in the developing rabbit and human embryos, experiments on rabbit embryo’s yield more reliable results for human embryology. The article has some rare images on normally developing rabbits and breaks the developmental stages down (in days) describing the observable characteristics that form (eg. Limb development & body formation).
I have decided to use the image provided in the journal.

Definitely worth reading people, follow the link!

http://content.karger.com/produktedb/produkte.asp?typ=fulltext&file=FDT2003018006422

'''Article 3'''

'''Acheiropodia is caused by a genomic deletion in C7orf2, the human orthologue of the Lmbr1 gene''' --[[User:Z3187802|Vishnnu Shanmugam]] 04:32, 2 September 2009 (EST)

''P. Ianakiev, M. J. van Baren, M. J. Daly, S. P. A. Toledo, M. G. Cavalcanti, J. Correa Neto, E. Lemos Silveira, A. Freire-Maia, P. Heutink, M. W. Kilpatrick, P. Tsipouras''
''Am. J. Hum. Genet. 68:38–45, 2001''
''Department of Pediatrics, University of Connecticut Health Center, Farmington, CT;''
''Department of Clinical Genetics, Erasmus University, Rotterdam;''
''Whitehead Institute for Biomedical Research, Cambridge, MA;''
''LIM/25-D, University of Sao Paulo School of Medicine,''
''And Private Practice, Sao Paulo;''
''Private Practice, Porto Alegre, Brazil;''
''Department of Genetics, UNESP-Universidade Estadual Paulista, Botucatu SP, Brazil''

'''Summary'''

The article describes the developmental abnormality Acheiropodia can be passed down genetically from parent to offspring. Acheiropodia (also known as Horn Kolb Syndrome) is a condition where the distal extremities of the embryo fail to form. Although it is not fatal, the individual endures a very difficult life without hands and feet. The article notes that the disorder only affects the development of the limbs and has no other reported manifestations. The article defines this to be an autosomal recessive disorder which means that two copies of an abnormal gene must be present in the affected individual in order for the disease to develop. Thus, each parent passes an abnormal gene to the offspring. It is interesting to note the process of the malformation from genotype to phenotype: small deletions on the chromosomes produce abnormal genes, the abnormal genes are then passed down to the offspring, the offspring that inherits two of the abnormal genes is unable to code for the correct proteins and as a result, there is failure in normal development of limb extremities in the embryo phenotype. The article also has a shocking image of an individual with Acheiropodia which highlights the extent to which it can impact a person’s life and the urgent need to find a cure.

Read more about the exact nature of the abnormal gene using the link.

http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=1109034

'''Article 4'''

'''Epidemiology of congenital clefts of the lip and palate''' --[[User:Z3187802|Vishnnu Shanmugam]] 04:32, 2 September 2009 (EST)

''JOHN C. GREENE'' ''D.M.D. ,M.P.H.'' ''Public Health Rep. 1963 July; 78(7): 589–602''

'''Summary'''

This review article combines research to study the factors causing the developmental abnormalities cleft palate and cleft lip in populations. “Cleft palate (palatoschisis)” and “cleft lip (cheiloschisis)” are the terms used to describe the non- fusion of the upper lip, hard or soft palate and typically occur during the gestation phase of embryonic development. The article tables the occurrence of cleft palate and cleft lip in populations of people in various cities across the world. It also compares the occurrence of cleft palate and cleft lip in males and females. The article finds that the incidence of cleft palate and cleft lip is:

*Is random in males and females (ie. Occurs approximately evenly in both sexes)

*Is random in people living in different cities

*Is higher in children of mothers over the age of 35

*Is higher in white populations and lower in the negro populations which suggests possible role of environmental factors

*No concrete proof that cleft palate and cleft lip is hereditary

*Is higher in rats exposed to radiation and those fed riboflavin

*Is higher in rabbits and other lab animals exposed to higher stress through cortisone injections

Although the article is now quite ancient, it is interesting to note the incidence of cleft palate and cleft lip among people. It also shows the historical foundation of research into the causes of cleft palate and cleft lip through animal experimentation.

Read more about cleft palate epidemiology using the link.

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1915191

'''Article 5'''

'''Chromosome abnormalities in human embryos''' --[[User:Z3187802|Vishnnu Shanmugam]] 00:10, 13 September 2009 (EST)

''Santiago Munne & Jaques Cohen The Center for Reproductive Medicine and science of Saint Barnabas Medical Center, New Jersey, USA Human Reproductive Update 1998, Vol. 4, No. 6 pp. 842-855 European Society of Human Reproduction and Embryology''

'''Summary'''

As the title suggests, this article focuses on chromosomal abnormalities in the developing human embryo. To understand this article, it is necessary to first establish some basic definitions that are used throughout the article. Aneuploidy can be defined as the occurrence of one or more extra or missing chromosomes leading to an unbalanced chromosome number. Although most babies with an unbalanced amount of chromosomal material miscarry during the first trimester of pregnancy, those that are born have crippling conditions such as:

* Birth defects

* Turner's syndrome (disorder where a female child is born with only 1 X chromosome)

* Down's syndrome (disorder where child is born with 3 copies of chromosome 21)

* Edward's syndrome (disorder where child is born with 3 copies of chromosome 18)

* Patau's syndrome (disorder where child is born with 3 copies of chromosome 13)

* Klinefelter's syndrome (disorder where male child is born with 2 copies of the X chromosome and 1 Y chromosome)

Polyploidy is a type of aneuploidy where the baby has three, four, or more sets of chromosomes instead of the two present in diploids. Chromosomal mosaicism is when different cells within an individual, who has developed from a single fertilized egg, have a different chromosomal makeup. Most commonly there will be some cells with a typical number of chromosomes (46 chromosomes) and other cells with an altered number or structure of chromosomes.

The article explores the possible causes of chromosomal abnormalities resulting from pregnancy though techniques such as IVF (In-Vitro Fertilization) and ICSI (Intracytoplasmic Sperm Injection). It also analyses the role of FSH (follicle stimulation hormone), temperature, water and light in chromosomal abnormalities.

The article finds:

* High FSH concentration increases likelihood of chromosomal abnormalities

* ICSI & IVF techniques have increased likelihood of chromosomal abnormalities

* Chromosomes exhibit temperature sensitivity and changes in temperature can cause chromosomal abnormalities

Although the article makes a number of findings, it is yet to be backed up with convincing evidence; the article has some really cool images of the developing embryo soon after fertilization. Overall, an interesting read.

Interested? Follow the link!

http://humupd.oxfordjournals.org/cgi/reprint/4/6/842.pdf

'''Article 6'''

'''Evaluation of the Safety and Pharmacokinetics of the Multi-Targeted Receptor Tyrosine Kinase Inhibitor Sunitinib During Embryo–Fetal Development in Rats and Rabbits''' --[[User:Z3187802|Vishnnu Shanmugam]] 00:10, 13 September 2009 (EST)

''S. Patyna, J. Haznedar, D. Morris, K. Freshwater, G. Peng, J. Sukbuntherng, G. Chmielewski, and D. Matsumoto''
''Pfizer Global Research and Development, San Diego, California''
''Roche LLC, Palo Alto, California''
''Pfizer Global Research and Development, Kalamazoo, Michigan''
''Xenoport Inc., Santa Clara, California''
''Pfizer Global Research and Development,'' ''Groton, Connecticut '' ''Birth Defects Research (Part B) 86:204–213 (2009)''

'''Summary'''

The article looks at how toxicity affects embryo-fetal development. The article describes the abnormal changes that occur when Sunitinib (an oral inhibitor of multiple receptor tyrosine kinases) is administered to pregnant rabbits and rats. This experiment was performed in an attempt to mirror the effects of antiangiogenic agents used in cancer treatment. Sunitinib is an antiangiogenic agent and the use of antiangiogenic agents is not recommended for treating cancer in pregnant patients because of the potential harm to embryo-fetal development. Angiogenesis (the formation of blood vessels) plays a critical role in embryo–fetal development and antiangiogenic agents slow down and/or stop the formation of blood vessels in order to control cancer and stop its spread. In pregnant patients however, this has the potential to adversely affect the developing embryo and these adverse effects is what is investigated in this article.

The article finds the antiangiogenic agent Sunitinib at toxic levels can result in:

* Embryo death

* Fetal skeletal malformations including vertebrae malformation and cleft lip/palate

* Teratogenic effects in rabbits

* Decreased maternal and fetal body weight

This article is a recent study and provides important findings regarding the use of antiangiogenic agents, especially during pregnancy. Although the maternal effects are minimal, the adverse effects to the embryo are significant and permanent. The article makes good use of tables and graphs to juxtapose pieces of information and to show trends. It is very interesting to note the extent to which chemicals can impact the vulnerable developing embryo.

Read more at link. (Use institutional login from UNSW computers)

http://www3.interscience.wiley.com/journal/122262246/abstract?CRETRY=1&SRETRY=0

------
thank you so much Vishnuu~~^^ from Juliana
-----
I also changed the format if you guys dont mind--[[User:Z3126328|Jin Lee]] 18:33, 31 August 2009 (EST)
----

Hey '''Vishnuu''', that link you found with the stages is awesome! thanks so much. Do you know if i am allowed to use the embryo pics in that article on our wiki page?? i'm not sure about the copyright rules. It says at the bottom of the article "Reproduced with permission of the copyright owner. Further reproduction prohibited without permission."
Does this mean we can only provide a link to it on our page? if so that's a shame, because those pics were fantastic!! '''SUM'''

Oh i also added an introduction - sum

Hey Sum,
Unfortunately, since its copyright protected we can't use the image directly......but there is a way of getting around it....You can modify the image using picture editing tools, then simply reference where the original picture came from and state that it has been modified by you. Alternatively, you can trace around the picture and provide only an outline (this will be very difficult to do with detailed pictures, a good picture editing software is recommended). Either way according to whats written under '''editing basics''' we need to include a picture that has been drawn up ourselves in the project. Also, not sure if you are aware, but the project is NOT due on Thursday (3rd September), Dr. Hill has very generously given everyone an extension till after mid-session break. --[[User:Z3187802|Vishnnu Shanmugam]] 02:35, 2 September 2009 (EST)

==Julianna's Research==
[http://netvet.wustl.edu/species/rabbits/rabtmodl.txt]
HISTORY OF THE RABBIT (IN RESEARCH)

A. Discovered in Spain about 100 B.C.
B. Domesticated in the 1500's
C. Standardization of breeds in 1800's
1. Research Uses
a. 1852: Rabbits have DL-hyoscyamine
(a) Can survive belladonna
(b) Endogenous atropine esterase
b. 1884: Pasteur develops rabies vaccine
c. 1891: Heape performs embryo transfer
(a) Influence on phenotype of the
uterine environment
d. 1908: Ignatowsky produces atherosclerosis
(a) Fed diets of milk, meat, and
eggs
(b) Produced intimal lesions
(c) Believed lesions due to protein
e. 1928: Demonstrated intranuclear development
of herpes virus
f. Graafian follicle was first observed
g. Coat colors and Mendelian inheritance
h. Immunology studies
i. Testing of human use products
j. Basic science studies
k. Diagnostic requirements
l. Eye Research
m. Pyrogen testing
n. Fetal drug induced teratology
o. Parasite research

LITERATURE REVIEW OF RABBIT USE

A. 1956 to 1800 ... Over 8000 citations
B. 1966 to 1987 ... 130,000 citations linking the rabbit to
all areas of research
C. 1988 to present ... 821 citations under the search
criteria: Rabbit: Model: Human Disease
D. Numbers of Rabbits Used (APHIS; ILAR records 1989)

1967 504,500
1978 439,986
1982 547,312
1983 466,810
1984 529,101
1985 544,621
1986 521,773
1987 534,385

ADVANTAGES OF USING RABBITS
A. Provides repeatability of animal model studies
B. Large enough for single samples
C. Many stocks/strains as animal models
D. Easily managed
E. Quality of immunologic products
F. Ease of reproductive control

DISADVANTAGES OF USING RABBITS
A. Most colonies are a storehouse of diseases
B. Extremely variable to responses to general anesthetics

[http://www.ncbi.nlm.nih.gov/pubmed/18430597]
The rabbit as a model to study asthma and other lung diseases.Keir S, Page C.
Sackler Institute of Pulmonary Pharmacology, Division of Pharmaceutical Sciences, 5th Floor Hodgkin Building, King's College London, Guy's Campus, London SE1 9RT, UK.

No single animal model is able to reproduce all the features of human asthma. However, the similarities between neonatally immunised rabbits and human asthma highlight the value of this model in the investigation of asthma pathophysiology and in the development of therapeutic agents. Airway inflammation and airway responses to various stimuli including histamine, adenosine 5'monophosphte and antigen in allergic rabbits have shown similarities with the responses observed in asthmatics. Furthermore, functional studies in rabbit airways show they are poorly responsive to capsaicin as are human airways. Chronic pre-treatment with capsaicin desensitises the TRPV(1) receptor enabling studies into the effect of this drug in both rabbits and man. The allergic rabbit model has been used extensively in assessing the various classes of anti-asthma drugs and is sensitive to similar drugs as patients with asthma, including beta-adrenoceptor agonists, corticosteroids, phosphodiesterase inhibitors and theophylline. This article highlights the usefulness of the rabbit as a species to study lung biology.

[http://www.ncbi.nlm.nih.gov/pubmed/8447943]
Effects of strain and embryo transfer model (embryos from one versus two donor does/recipient) on results of cryopreservation in rabbit.Vicente JS, García-Ximénez F.
Departamento de Ciencia Animal, Universidad Politécnica de Valencia, Spain.

Differential effects of 2 transfer models for normal thawed embryos of 1 donor doe were studied on the offspring rate and their embryo survival at birth from 3 selected rabbit strains (SY and SB: synthetic strains, NZ: New Zealand White). Morulae were obtained 64-66 h post-coitum from 93 adult does treated with 25 IU of hCG (SY:36, NZ:27, SB:30). Morphologically normal morulae were frozen in the presence of 1.5M DMSO and stored in liquid nitrogen. Normal thawed embryos were transferred into the oviducts of synchronized recipient does of the same strain 48 h after being injected with 25 IU of hCG (SY:28, NZ:21, SB:24). Each recipient received embryos from 1 (single transfer) or 2 different donor does (double transfer). Significant differences were observed in the post-thawing percentage of normal embryos between strains (SY:95 +/- 1% and SB:85 +/- 3%, P < 0.05; NZ: ,91 +/- 2%). After transfer, no significant differences were observed in pregnancy rate and offspring rate between the transfer models, whereas significant differences were only found in survival rate when all transfers were analyzed (double: 24 +/- 4% vs single: 14 +/- 3%, P < 0.05). An effect of strain was detected in the pregnancy rate (NZ: 33% vs SB: 71%, P < 0.05; SY: 61%) and in the survival rate per donor doe on pregnant recipient doe (SY: 42 +/- 5 vs SB: 19 +/- 5, P < 0.05; NZ: 34 +/- 7%). These results suggest a differential embryo sensitivity with respect to their genetic origin in both the freezing-thawing and transfer procedures.

--[[User:Z3126328|Jin Lee]] 13:06, 3 September 2009 (EST)

[http://www.ncbi.nlm.nih.gov/pubmed/14064965?log$=activity]GROSS EFFECTS ON RABBIT EMBRYOS AND MEMBRANES OF X-IRRADIATION IN THE BLASTOCYST STAGE.

[http://www.ncbi.nlm.nih.gov/pubmed/11139224?ordinalpos=408&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum]Onset of zygotic transcription and maternal transcript legacy in the rabbit embryo.Brunet-Simon A, Henrion G, Renard JP, Duranthon V.
Laboratoire de Biologie du Développement, INRA, Jouy en Josas Cedex, France.

Onset of zygotic transcription is progressive from the one-cell stage onward in the rabbit embryo. Maternal transcripts remain fairly stable until the 8-16 cell stage when major transcriptional activation of the zygotic genome takes place. To understand the mechanisms of the maternal-to-zygotic transition in the genetic information governing development, we asked whether a progressive synthesis of zygotic transcripts takes over the maternal molecules, or whether the synthesis of zygotic transcripts is very abrupt and independent of the persistence of the maternal counterparts. To answer this question, we set up mRNA differential display experiments comparing the mRNA content of rabbit embryos at different stages during the preimplantation period. We isolated eight zygotic transcripts whose synthesis is abruptly turned on at the 8-16 cell stage. These transcripts are involved in general cellular metabolism and their maternal counterparts are still present up to the four-cell and even the 8-16 cell stage. This identification of early zygotic transcripts suggests that global long range modifications of chromatin structure result in a rapid increase in transcription rates during the major transcriptional activation of the zygotic genome.

[http://www.ncbi.nlm.nih.gov/pubmed/11245264?ordinalpos=409&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum]
Reconstruction of the heteroparental diploid condition in rabbit zygotes by nuclear transfer.Escribá MJ, García-Ximénez F.
Departamento de Ciencia Animal Universidad Politécnica de Valencia, Spain. mescriba@dca.upv.es

Studies on genomic imprinting showed that parental genomes have complementary roles during embryogenesis, are both essential and need to be synchronized in their embryonic stage for successful development to term. To our knowledge, these studies have not been performed in species other than mice. We studied the in vitro and in vivo development of reconstructed zygotes by combining female haploid nuclear donors and androgenetic hemizygous recipients. Haploid donor embryos at the 8- or 32-cell stage were obtained from electroactivated young rabbit ova (eight pulses maximum, consisting of 0 6 kVcm(-1) for 60 microsec each, 38 min apart) which were further cultured for 24 h or 32 h. Couplets formed by both the haploid male hemizygous recipients and haploid female donor cells were electrofused (2.2 kVcm(-1) for 60 microsec duration each, 30 min apart) and their nuclear configuration determined 122 of those fused (43%: 122/286) were diploid. Reconstructed diploid zygotes developed in vitro up to the compacted morula, blastocyst and hatched stages (1/8-nuclei x 50%, 18% and 9% vs. 1/32-nuclei: 47%, 25% and 19%; P > 0.05), respectively. In embryo transfer assays, both 1/32-reconstructed zygotes and control, non-manipulated zygotes were transferred to synchronized does Four live reconstructed fetuses (4/49: 8 1% survival rate) and five in regression stage (9/49: 18% implantation rate) were observed on Day 21 post-ovulation, whereas from control zygotes, 11 fetuses were alive (11/53 21% fetal survival rate) and 2 degenerated (13/53 x 24 5% implantation rate). Similar results were obtained from a final experiment, in which development was allowed to progress to term. Six live rabbit pups derived front experimentally reconstructed zygotes (11%; 6/54) and three fetuses in regression stage were obtained; values slightly lower than those derived from non-manipulated and transferred control zygotes (18% 9/50, live born rate).

[http://www.ncbi.nlm.nih.gov/pubmed/11589623?ordinalpos=412&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum]
Effects of leukaemia inhibitory factor on endometrial receptivity and its hormonal regulation in rabbits.Liu CQ, Yuan Y, Wang ZX.
Shanghai Institute of Planned Parenthood Research, Shanghai, P. R. China.

The effects of hormones on production of leukaemia inhibitory factor (LIF) and the uterine receptivity in rabbits were studied. In ovariectomised rabbits, LIF protein was not detected in control but upregulated by progesterone alone. Oestrogen had a slightly negative effect when the rabbits were treated with both oestrogen and progesterone. Mifepristone (Mi) inhibited the progesterone-stimulated production of LIF in rabbit uterus. The transfer of embryos to LIF-treated recipients significantly increased pregnancy rate (70%) and implantation rate (27%) as compared with control (pregnancy rate=40% and implantation rate=17%). The transfer of embryos to LIF and mifepristone-treated recipients significantly decreased pregnancy rate (30%) and implantation rate (9%). The results indicated that LIF protein had a beneficial effect on uterine receptivity and mifepristone prevented this effect. Copyright 2001 Academic Press.

[http://www.ncbi.nlm.nih.gov/pubmed/8447943]
Effects of strain and embryo transfer model (embryos from one versus two donor does/recipient) on results of cryopreservation in rabbit.Vicente JS, García-Ximénez F.
Departamento de Ciencia Animal, Universidad Politécnica de Valencia, Spain.

Differential effects of 2 transfer models for normal thawed embryos of 1 donor doe were studied on the offspring rate and their embryo survival at birth from 3 selected rabbit strains (SY and SB: synthetic strains, NZ: New Zealand White). Morulae were obtained 64-66 h post-coitum from 93 adult does treated with 25 IU of hCG (SY:36, NZ:27, SB:30). Morphologically normal morulae were frozen in the presence of 1.5M DMSO and stored in liquid nitrogen. Normal thawed embryos were transferred into the oviducts of synchronized recipient does of the same strain 48 h after being injected with 25 IU of hCG (SY:28, NZ:21, SB:24). Each recipient received embryos from 1 (single transfer) or 2 different donor does (double transfer). Significant differences were observed in the post-thawing percentage of normal embryos between strains (SY:95 +/- 1% and SB:85 +/- 3%, P < 0.05; NZ: ,91 +/- 2%). After transfer, no significant differences were observed in pregnancy rate and offspring rate between the transfer models, whereas significant differences were only found in survival rate when all transfers were analyzed (double: 24 +/- 4% vs single: 14 +/- 3%, P < 0.05). An effect of strain was detected in the pregnancy rate (NZ: 33% vs SB: 71%, P < 0.05; SY: 61%) and in the survival rate per donor doe on pregnant recipient doe (SY: 42 +/- 5 vs SB: 19 +/- 5, P < 0.05; NZ: 34 +/- 7%). These results suggest a differential embryo sensitivity with respect to their genetic origin in both the freezing-thawing and transfer procedures.

[http://www.ncbi.nlm.nih.gov/pubmed/14564113]
'''Developmental stages in the rabbit embryo: guidelines to choose an appropriate experimental model.'''Beaudoin S, Barbet P, Bargy F.
Department of Pediatric Surgery, Groupe Hospitalier Cochin-Saint-Vincent de Paul, Paris, France. sylvie.beaudoine@svp.ap-hop-paris.fr

Researchers involved in the field of congenital malformations are often forced to work on an animal model. Both accurate description of its normal development and comparative staging with human development will be mandatory. To complete the lacking medical literature, we herein provide such data for the rabbit model. Sampled rabbit embryos were staged using the Carnegie criteria, in order first to determine if they were consistent with the rabbit developmental pattern, and second to compare this pattern with the human one. Our results show a suitable comparison of rabbits and humans in early developmental stages, except for the neural growth. Copyright 2003 S. Karger AG, Basel

2009 Group Project 1

2009-10-14T12:38:34Z

Z3185685: /* Timeline of Embryo Development */

[[File:Rabbits.png|right|400 px]]

== '''THE RABBIT (ORYCTOLAGUS CUNICULUS)''' ==

==Introduction==

[[File:Isidro_Martinez.jpg‎|left|175 px]]

Several characteristics of the rabbit make it an excellent model for study. This will be further explored in "The History of Model Use" section of this page. Many studies have resulted in the development and improvement of various micro-manipulation techniques such as the production of transgenic rabbits. Unlike many other species such as the chick or rat, relatively little is known about the development of a rabbit. Nevertheless, it is still an appropriate animal model as the results from many experiments are significant to that of other mammals, including humans. (55)

A rabbits potential for reproduction is high, breeding from the early stages of 3 to 4 months of age. A mature female rabbit can be pregnant from 6 to 8 months in a year, producing up to 30 to 40 young in this time. (56)

==History of Model Use==

'''WHY are we using rabbits?'''

ADVANTAGES
*Provides repeatability of animal model studies
*Large enough for single samples
*Many stocks/strains as animal models
*Easily managed
*Quality of immunologic products
*Ease of reproductive control

DISADVANTAGES
*Most colonies are a storehouse of diseases
*Extremely variable to responses to general anesthetics

'''Brief timeline of rabbit embryo model use'''

*1672- de Graaf found the Graffian follicle.
*1890- Walter Heape succeeded first mammalian embryo transfer
*1906- FT Lewis discovered the development of the lymphatic system in rabbit embryos.
*1941- Dr. Pincus succeeded in keeping rabbit embryos developing in the test
*1968- Edwards and Gardner successfully performed the first known embryo biopsy on rabbit embryos

=== Regnier de Graaf (1641–1673) ===
[[image:Ovary_Graaf.jpg|thumb|250px|left|drawing of ovary]]
[[File:Regnier de Graaf.jpg|right]]

'''Discovery of the Graafian Follicles'''

In 1672 de Graaf published ''The Generative Organs of Women'', which was primarily a study of development in the rabbit. When de Graaf discovered large, round welling on the ovaries of rabbits, he assumed they were mammalian eggs. De Graaf also described the corpus luteum.

He summarised the previous works from anatomists, but unable to experience the amazing benefits made by microscopy.
But Antonie van Leeuwenhoek (A microbiologist, 1632 - 1723) argued that the structures now known as Graafian follicles could not be eggs. Haller suggested that the egg might be formed by the coagulation of the fluid within the Graafian follicle. De Graaf noted that the “egg” did not contain a tiny embryo, but he thought it did contain the “germ” of the future organism. (3)

=== Walter Heape (1855-1928) ===
'''First case of embryo transfer experiments'''

On 27 April 1890, Walter Heape (a professor and physician at the University of Cambridge, England) transferred rabbit embryos from one mother to another. (7) One rabbit mother became pregnant and delivered young from the transferred embryos. This was the first mammalian embryo transfer experiment to be successfully completed. His embryo transfer work in perspective as it relates to other contributions of this pioneer in reproductive biology.(7)

In 1891, Walter Heape had been conducting research on reproduction in numerous animal species. Working with two species of rabbits, he flushed embryos from the rabbit fallopian tubes of one breed (Angora) and placed them into the uterus of a recently mated Belgian hare. In the resulting litter, there were 4 Belgians and 2 Angoras. Heape proved that it was possible to take preimplantation embryos and transfer them to a gestational carrier without affecting their development.(7)

===Dr. Gregory Goodwin Pincus (1903-1967) ===

'''Contraceptive pill'''

Dr. Pincus began studying hormonal biology and steroidal hormones early in his career. His first breakthrough came when he was able to produce in vitro fertilization in rabbits (by using chemicals) in 1934. Throughout their hormonal contraceptive research Pincus, along with reproductive physiologist Min Chueh Chang, found out progesterone would act as an inhibitor to ovulation. They co-invented the combined oral contraceptive pill.[2][6]

===Genetic Diagnosis===
In 1968, Robert Edwards and David Gardner reported the successful sexing of rabbit blastocysts, setting the first steps towards PGD (Preimplantation Genetic Diagnosis). It was not until the 1980s that human IVF was fully developed, which coincided with the breakthrough of the highly sensitive polymerase chain reaction (PCR) technology. Handyside and collaborators' first successful attempts at testing were in October 1989 with the first births in 1990 though the preliminary experiments had been published some years earlier. In these first cases, PCR was used for sex determination for patients carrying X-linked diseases.(12)

==Timeline of Embryo Development==

The following is a timeline, adapted from Cibelli (2002), of the main events of preimplantation development in rabbits. The time is measured in hours post-mating and shows the embryo stage (cell number) in each time scale.

[[File:Morula1.JPG|right|200 px|thumb|A day 2 early morula]]

'''12-14 hours:''' Oocyte; Fertilization

'''18-20 hours:''' Zygote; Pronuclear formation

'''24-26 hours:''' Two cell

'''30-32 hours:''' Four cell

'''38-40 hours:''' Eight cell; Maternal-zygotic transition

'''46-48 hours:''' Sixteen cell

'''54-56 hours:''' Morula (32 cell); Compaction and transport to uterus

'''64-66 hours:''' Compact morula (64 cell); Morula-blastocyst transition

'''76-78 hours:''' Early blastocyst (128 cell)

'''84-86 hours:''' Expanded blastocyst (256 cell); Blastocoels expansion

'''94-96 hours:''' Hatched blastocyst (512 cell); Hatching

The following shows a diagrammatic representation of the relative sizes of rabbit embryos. The sizes do not include the embryonic coverings such as the zona pellucida and mucin coat. This diagram has been adapted from Warner (2003).

[[File:Sizeswithscale.JPG‎]]

The following timelines show a comparison of the developmental stages between human and rabbit embryos. They have been adapted from Derelanko (2008). "The similarities of this developmental pattern in humans and rabbits, suggests that the same growth increment is required to achieve the same stage. The main difference observed between human rabbit gestational duration is due to the fetal growth phase. The reason for this may be due to birth weight, lifetime and the neural complexity of the species." (59)

[[File:Timeline_rabbit.JPG]]

The following timelines have been adapted from a study carried out by Beaudoin et al. on the development of rabbit embryos.

==='''Body Form'''===

'''8.5 days''': Embryo thickens. First somites appear. Rostral neuropore closes. Caudal neuropore remains open

'''9.5 days''': Dorsal curvature begins. Cardiac mass bulges under cephalic pole.

'''10.5 - 13.5 days''': Dorsal curvature increases. Body thickens. Softening of the cephalic domination straightens the embryo.

'''17.5 days''': Neck becomes visible.

==='''Limb Development'''===

''' 9.5 days''': Rostral limb bud appears

'''10.5 days''': Caudal limb bud appears

'''12.5 days''': Hand plate becomes present. Limbs become disposed.

'''13.5 days''': Foot plate and finger rays become visible.

'''14.5 days''': Rostral and caudal limbs become parallel.

'''15.5 days''': Elbow appears.

'''16.5 days''': Fingers start to elongate.

'''17.5 days''': Knee becomes visible

'''19.5 days''': Hands and feet merge on the midline. Three segments of limbs become distinguished.

==='''Abdominal Wall Development'''===

'''9.5 days''': Abdominal wall is limited to the embryonic pedicle under the cardiac mass.

'''13.5 days''': First intestinal loops appear in the umbilical cord.

'''14.5 days – 17.5''': Rapid intestinal development in the cord.

'''15.5 days''': Abdominal vesicles can be observed.

'''16.5 days''': Cecal bud becomes present outside the abdomen

'''18.5 days''': Bowel returns to the abdominal cavity and umbilical ring closes.

==='''Cephalic Development'''===

'''9.5 days''': One cerebral vesicle can be seen. Pharyngeal arches as optic vesicle are present.

'''10.5 days''': Three arches are distinguished in the cephalic pole.

'''11.5 days''': Three cerebral vesicles present. Optic plate is distinguished.

'''12.5 days''': Face develops nasal, maxillar and mandibular buds. Lens vesicle is closed. Five cerebral vesicles exist.

'''14.5 days''': The ear becomes refined. Face can be distinguished from the brow.

'''18.5 days''': Eyelid appears, covering the eyes.

==Staging==

The following stages have been adapted from Beaudoin et al. (2003). Table 1 represents at each age its corresponding stage defined by the Carnegie classification

{| class="wikitable" style="text-align:center; width: 800px; height:1000px" border="1"
|+'''Table 1. Rabbit developmental stages using Carnegie classification'''

|- style="height:50px"
! '''Stage''' !! '''Days''' !! '''Event''' !! '''Image'''
|- style="width:200px"
! width="50" | 10
| width="50" | 8.5 || First somites appear, rostral neuropore closes
|- style="height:75px"
! 12
| 9.5 || Rostral limb bud, embryonic pedicle, caudal neuropore closes, one cerebral vesicle, pharyngeal arches, completion of optic vesicle
| [[file: 9.5new.JPG|100px]]
|- style="height:75px"
! 13
| 10.5 || Dosral C-shaped curvature, caudal limb bud, prominent cardiac swelling, four pharyngeal arches
| [[file: 10.5new.JPG|100px]]
|- style="height:75px"
! 14
| 11.5 || Three cerebral vesicles, optic plate, mesonephric ridge
|- style="height:75px"
! 15
| 12.5 || Hand plate, wheel ray limbs, lens vesicle closes, five cerebral vesicles, facial buds, vertebrae
| [[file: 12.5new.JPG|100px]]
|- style="height:75px"
! 16
| 13.5 || Foot plate, finger rays, prominent liver, intestinal loops, auricular hillocks
| [[file: 13.5new.JPG|100px]]
|- style="height:100px"
! 19
| 14.5 || Cuboidal body, trunk straightens, parallel limbs, toe rays, modeled face, visible auricle
| [[file: 14.5new.JPG|100px]]
|- style="height:75px"
! 20
| 15.5 || Elbow, fingers elongate, notches between toe rays
| [[file: 15.5new.JPG|100px]]
|- style="height:75px"
! 21-22
| 16.5 || Toes free, cecal bud in intestinal hernia
| [[file: 16.5new.JPG|100px]]
|- style="height:75px"
! 22-23
| 17.5 || Knee, neck, eyelids
| [[file: 17.5new.JPG|100px]]
|- style="height:75px"
! 23
| 18.5 || Hands and feet join at the midline, closure of abdominal wall, eyelids cover eyes
| [[file: 18.5new.JPG|100px]]
|-
| colspan="4" align="center"| Following this stage fetal appearance is completed, organogenesis is achieved
|}

==Genetics==

===Sequencing===
The National Human Genome Research Institute selected the European rabbit (Oryctolagus cuniculus) for whole genome sequencing to enhance their understanding of the human genome and use it experimentally for an animal model for human disease. (8)

The rabbit has been sequenced twice by The Broad Institute as part of the mammalian genome project. It is now currently undergoing 7 more sequencing projects. Its sequencing is made by the Whole Genome Shotgun (WGS) and assembly method. (9) This is when genomic DNA is sheared into small pieces of approximately 2000 base pairs which are then cloned into plasmids and sequenced on both strands. Once the contig fragments are read, realigned and reassembled by computer algorithms, it will give the overall sequence. (10) (11) The image below shows diagramatically how the two types of sequencing are different. The same techniques are used for sequencing the human genome (in 2003). [A contig is a set of overlapping DNA segments, derived from a single source of genetic material, from which the complete sequence may be deduced.

The whole genome shotgun (WGS) has serious gaps, yet the information has already proven useful for immunological as well as in silico studies. Deeper 7x coverage started in September 2007. The NCBI Rabbit Genome Resources site has links to searches for genes in the assemblies of the 2x WGS sequence at Ensembl and UCSC.(12) [http://www.broadinstitute.org/models/europeanrabbit/ Rabbit Genome Project]

[[File:WGS_sequencing.gif‎|center|800 px]]

===Genome===
The Rabbit genome was published by two groups (9)
# Lindblad-Toh,K., Chang,J.L., Gnerre,S., Clamp,M. and Lander,E.S. published their admission of 84024 bases on May 5th 2005 to The Broad Institute (USA) by shotgun sequencing
# Di Palma,F., Heiman,D., Young,S., Gnerre,S., Johnson,J., Lander,E.S. and Lindblad-Toh,K. published their admission of 84024 bases on August 3rd 2009 to The Broad Institute (USA) by shotgun sequencing.
The rabbit's genome is sequenced and on display in the Nucleotide Data Bank. It is too long to produce here. A link to the data bank is provided: [http://www.ncbi.nlm.nih.gov/nuccore/256946799/ Rabbit Genome from the Nucleotide Data Bank]

[[File:8cellembryo.jpg|thumb|Individual mitochondria (arrowheads) of an 8cell Rabbit embryo]]

The rabbit genome was sequenced in 2005 by Ensembl and managed to produce: (13)
* 2,076,044,328 supercontigs (ordered Contigs with gaps)
* 495 Known protein-coding genes
* 11,357 Projected protein-coding genes
* 2,343 RNA genes
* 212,581 Gene exons
* 20,311 Gene transcripts

For further research the taxonomy ID number for the Rabbit is: 9986 [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=9986&lvl=3&lin=f&keep=1&srchmode=1&unlock/ Taxonomy Data]

===Mitochondrial Genome===
The mitochondiral genome (mtDNA) of the rabbit was sequenced on November 14th 2006 with 17245 base pairs/nucleotides in circular form. Apparently the "length is not absolute due to the presence of different numbers of repeated motifs in the control region".
PMID 9653643

The image to the right shows the mitochondria during cell division and multiplication in embryo development.

=== Chromosomes ===
Over the years there have been various data suggesting the diploid chromosomal number for the rabbit may range from 22-42. However through recent research and an abundance of trials suggest that the rabbit does indeed have 22 different chromosome pairs existing in each cell of the rabbit. (16)(17) The sex chromosomes of the rabbit are of X-Y type convincingly (17). In a study in Bombay it confirmed that a rabbit has 2n = 44 chromosomes. There were 21 pairs of autosomes, out of which 1 to 6 were metacentric, 7 to 11 submetacentric, 12 to 17 subtelocentric and 18 to 21 acrocentric, plus the sex chromosomes. The image to the left shows a female rabbit with no chromosomal abnormalities. (19)

'''Comparison to human chromosome:'''

Rabbit chromosomes 12, 19 and X were found to be completely homologous to human chromosomes 6, 17 and X, respectively. All other human chromosomes were homologous to two or sometimes three rabbit chromosomes. (14) Chromosome 12 was shorter than chromosomes 13 and 14. (15) The image below illustrates the human chromosome (2n = 46).

[[File:Drawn chromosome.jpg|left|400 px]]

[[File:Karyotypehuman.gif|right|500 px]]

'''Abnormalities'''

These are generally more apparent during early embryo development in blastocysts from delayed fertilization. Some examples of abnormal development include cases of: (18)
* hypoploidy; 1 chromosome missing from a pair (2n = 43),
* double hypoploidy; 2 chromosomes missing from 2 different pairs (2n = 42),
* mosaicism (different chromosomal makeup in some cells).

Another study also found these abnormalities as well as: (19)
* autosomal trisomy (3 autosomes per pair),
* triploidy (extra set of chromsomes),
* mixoploidy (unequal number of chromosome sets in adjacent cells), and
* short arm deletion (deletion of parts of chromosomes).

A specific abnormality occurring in rabbits is the x-linked tremor. There is a mutation in exon 2 of the prteolipid-protein (PLP 1) gene, corresponding to the end of the first potential transmembrane domain of the protein. This disorder affects myelination of the central nervous system. OMIA ID:12 [http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=full_report&list_uids=100009169&log$=omiamaingene| Gene:100009169]

==Abnormal Development==

Abnormal embryological development is a vast field of study that has been the subject of recent research papers. Our investigation of abnormal development in rabbit embryology will focus on abnormalities commonly found in both rabbit and human embryos. We will explore the nature of these abnormalities in both humans and rabbits.

[[File:Normal v Abnormal.jpg|right|300 px|thumb|Brain MRI of patient with Hydrocephalus (left) compared to a normal brain (right). An obvious increase in ventricular size and a significant decrease in brain size is present.]]
[[File:Ventricle_Expansion.jpg|right|300 px|thumb|CSF accumulation in ventricles of brain increasing intracranial pressure.The pressure from the expanding ventricles force the brain and skull to grow outwards abnormally.]]

'''Hydrocephalus'''

Annually, one in every 1000 children born in Australia have hydrocephalus. Hydrocephalus occurs when excessive cerebrospinal fluid (CSF) accumulates in the brain and can result in severe disability and even death because the disorder can result in complete or near complete destruction of the cerebral cortex (22).

Children born with hydrocephalus typically exhibit abnormally large head circumference and bulging cranial fontanels as a result of increased intracranial pressure on the brain from the accumulating CSF (22,23). As CSF accumulates in the ventricles and CSF compartments of the brain, it expands forcing the brain to grow outward. The outward growing brain places pressure on the skull which in turn also grows outwards giving rise to an abnormally large head circumference and bulging cranial fontanels (22,24). It is generally acknowledged that children with hydrocephalus have mental retardation, often to the degree of being “vegetative” (24).

The serious consequences of this disease mean that much research is necessary to unearth methods of prevention and effective treatment. One of the modes of studying hydrocephalus is to use the rabbit experimental model where hydrocephalus can be induced in rabbit embryo’s. The injection of silicone oil into the cisterna magna of the brain is one way of inducing hydrocephalus in the rabbit embryo. The silicone oil obstructs the normal flow of CSF resulting in CSF accumulation in the brain leading to hydrocephalus (25). Another method of inducing hydrocephalus in rabbit embryo’s is by intentional vitamin A deprivation of pregnant dams. The vitamin A deficiency results in raised intracranial CSF pressure and aqueduct stenosis causing poor circulation of CSF leading to hydrocephalus (26,27). Although the exact function of vitamin A on brain development and CSF regulation is not fully understood, it is clear that Vitamin A has an important role in brain development and its normal functioning (27).
[[File:Rabbithhdrocephalus.jpg|center|300 px|thumb|Young rabbit with hydrocephalus caused by Vitamin A deficiency. Note the abnormally shaped cranium inflamed in appearance.]]

[[File:SpinabifidaMeningocele1.jpg|right|300 px|thumb|Spina Bifida Meningocele has characteristic damage to the meninges of the spinal cord which are pushed out through an opening in the vertebrae as a cyst filled with CSF.]]
[[File:SpinaBifidaMyelomeningocele.jpg|right|300 px|thumb|Spina Bifida Myelomeningocele is the most severe form of spinabifida where the damaged spinal cord protrudes out with damaged meninges as a cyst filled with CSF.]]
[[File:SpinaBifidaOcculta1.jpg|right|300 px|thumb|Spina Bifida Occulta is the least severe as the spinal cord and meninges are undamaged.]]

'''Spina Bifida'''

In Australia, the risk of spina bifida is 1 in every 500 pregnancies. Spina bifida is a type of neural tube defect where vertebrae (which normally cover and protect the spinal cord) are not completely formed but are divided resulting in the defective spinal cord and its coverings to protrude through the opening (28,29).

There are three main types of Spina Bifida differentiated by their characteristic features:

1)Spina Bifida Meningocele characterized by normal spinal cord, divided outer vertebrae and meninges surrounding the spinal cord protruding from the divided vertebrae as a cyst (1,28).

2)Spina Bifida Myelomeningocele characterized by split outer vertebrae with spinal cord and its meninges protruding from the divided vertebrae as a cyst. Commonly found at lumbar vertebral level (1,28,29).

3)Spina Bifida Occulta characterized unfused vertebral arches and exposed vertebral canal. Spinal cord and its meninges still located in vertebral canal (1,28).

All forms of spina bifida are potentially fatal and in those where the spinal cord is damaged severe consequence arise including and paralysis and loss of sensation at and below the level of damage spinal cord damage (29,33). There is a lot of Spina bifida research using rabbit models to test the effective methods of correcting spina bifida. The occurrence of natural spina bifida in rabbits is rare and for experimental purposes it can be surgically created in rabbit fetuses during gestation (31,32). The process involves aesthetical sedation of the maternal rabbit at day 22 of gestation; a midline laparotomy performed and the desired type of spina bifida lesion created on the exposed fetus using forceps. Different methods for correcting spina bifida can then be tested and its effectiveness analysed (30,33,34).
[[File:Rabbitspinabifida1.jpg|center|350 px|thumb|Rabbit newborn with Spina Bifida. Note the unfused, divided vertebrae and exposed spinal cord.]]

'''Brachydactylia & Acheiropodia'''

[[File:Malformation1.jpg|right|150 px|thumb|Acheiropodia in rabbit characterized by amputations of the limbs and extremities.]]

[[File:Rabbitmalformation3.jpg|left|150 px|thumb|X-Ray study of rabbit limbs with malformed phalanges due to Brachydactylia.]]

Brachydactylia and Acheiropodia are genetic disorders characterized by skeletal malformation of the hands and feet (36,36). In Brachydactylia, the malformations commonly involve abnormal shortening of fingers and toes due to poorly formed or absent bones (35). Acheiropodia is characterized by more severe skeletal malformations including bilateral amputations of the distal upper and lower extremities as well as aplasia of the hands and feet. Although it is not fatal, the individual endures a very difficult life without hands and feet (37).

The inheritance mechanism of this diseases can has been studied through experiment using rabbits. Rabbits with abnormal genes coding for Brachydactylia and Acheiropodia are selected and bred to produce offspring with the disease (36). Brachydactylia and Acheiropodia are autosomal recessive disorders which means that two copies of an abnormal gene must be present in the affected individual in order for the disease to develop. Thus, each parent passes an abnormal gene to the offspring (35,36). The process of the malformation progresses from genotype to phenotype; small deletions on the chromosomes produce abnormal genes, the abnormal genes are then passed down to the offspring, the offspring that inherits two of the abnormal genes is unable to code for the correct proteins and as a result, there is failure in normal development of limb extremities in the embryo phenotype (37,38).

==Current Embryology Research==

There is currently great excitement in research involving rabbits in the fields of transgenesis, cloning and stem cells. We shall explore research in these areas by discovering some of the techniques used and how they have been applied to the rabbit model.

[[File:Trans1.jpg|right|170 px]]
[[File:Trans2.jpg|right|170 px]]
[[File:Trans3.jpg|right|170 px]]
[[File:Trans4.jpg|right|170 px]]
[[File:Trans5.jpg|right|170 px]]

'''Transgenic rabbit'''

A transgenic organism is one whose genome also contains genes from another species (39). The aim of creating a transgenic organism is to obtain a favorable characteristic in the organism’s phenotype (41). This desired characteristic of phenotype is obtained by altering the organism’s normal genotype to include the gene from another species with the desired characteristic (39,40).

The production of a transgenic organism involves several steps summarized below:

1) The chromosome and the desired gene on it are identified in an organism (39).

2) The gene is isolated from its DNA strand. This involves “cutting” it out of its DNA strand using enzymes called restriction endonucleases. The restriction endonucleases cut DNA at specific site so the desired gene can be removed from the DNA strand. The cut ends are known as “sticky ends” (39,40).

3) Separate DNA sequences for regulation sometimes have to be added to ensure the gene will work (40).

4) The gene is then inserted with a promoter sequence into the fertilized egg cell of a new organism producing recombinant DNA (39,44). To do this, firstly the new organism’s cell DNA must first be cut and the desired gene incorporated into it. The same enzymes are used to cut the new organism’s cell DNA because the DNA stands from the two different organisms will form matching sticky ends that will be attracted to and connect with each other in a process is called “annealing” (39,40,44).

5) DNA ligases are sealing enzymes found in all living organisms that help make and repair DNA (39,40). The DNA ligases are added to the annealed DNA fragments to help strengthen the bonds of the new recombinant DNA. The recombinant DNA is now transferred into the new organism’s fertilized egg by microinjection (44).

6) As the embryo develops and the recombinant genetic code read, new proteins are synthesized which code for the new desired phenotype characteristic in the transgenic organism (39,40).

Transgenic rabbits can be created in the laboratory by gene microinjection into the fertilized rabbit oocyte (44). In April 2000, a transgenic rabbit named Alba was born containing a gene from a Pacific Northwest jellyfish. The gene which was injected into a fertilized albino rabbit oocyte allows the rabbit to synthesize the green fluorescent protein (GFP) that is characteristic of the Pacific Northwest jellyfish. When illuminated correctly, Alba glows a bright green (43,46).

Transgenic rabbits have important research purposes. Transgenic rabbits can be created to model retinal degeneration (44). Retinal degeneration is a common problem with aging and diseases such as diabetes, and frequently leads to complete blindness (42). A genetic retinal degeneration disease called retinitis pigmentosa (RP) is created in these rabbits by introducing the “Pro347Leu” mutation of the rhodopsin gene into fertilized rabbit eggs (43,44). As the rabbit grows, it develops the disease which becomes progressively worse (45).
The use of these transgenic rabbits ultimately leads to better understanding of the disease and more effective treatments (42). [[File:Transgenic rabbit.jpg|center|250 px|thumb|"Alba" A trangenic rabbit with a gene from a Pacific Northwest jellyfish that allows it to synthesize the green fluorescent protein (GFP) of the jellyfish.]]

[[File:Crabbit 1.jpg|right|170 px]]
[[File:Rabbit2.jpg|right|170 px]]
[[File:Rabbit3.jpg|right|170 px]]
[[File:Crabbit 4.jpg|right|170 px]]

'''Cloning'''

Cloning is a method of producing genetically identical organisms. The principle of cloning relies on “tricking” an egg cell to begin rapidly dividing into an embryo (39). In the normal fertilization process, two haploid sex cells unite to form a diploid zygote which begins rapidly dividing into an embryo (40). By replacing the haploid egg cell nucleus with a diploid somatic cell nucleus, the egg cell is tricked into thinking it is fertilized and hence begins rapidly dividing to form an embryo (39,40,41).

The process of cloning involves several steps summarized as the following using a rabbit example:

1) A somatic cell is obtained from a rabbit and the nucleus removed (39).

2) An egg cell is obtained from a donor rabbit and the nucleus of the egg cell removed using an enucleation needle. The cell is now called an enucleated egg cell (egg cell without a nucleus) (39,41).

3) The nucleus of the somatic cell is inserted into the enucleated egg cell (41).

4) The cell is now stimulated to divide by applying pulses of electric current (39).

5) The rapidly dividing cell develops in culture for a few days forming the early embryo (40,41).

6) The embryo is then implanted into the uterus of another rabbit similar to the egg cell donor. This rabbit is called the surrogate mother (40,41).

7) The embryo develops and the surrogate mother gives birth to a rabbit fetus with near identical genotype of the somatic cell donor (the small genomic difference is caused by the fetus obtaining mitochondrial DNA from the egg cell donor) (39,41).

The cloning of rabbits has been achieved by inserting the diploid nucleus of a rabbit fibroblast (the principal cells in connective tissue) into an enucleated oocyte (49). There is currently much focus on the creation of controversial but revolutionary interspecies hybrid embryos where the nucleus from a human somatic cells are implanted into an enucleated egg cell of another animal (50). The resulting embryo (known as a chimera) will be almost completely human genotype but will have genome from the other animal (48). In 2003, scientists at the Shanghai Second Medical University fused human cell with rabbit eggs creating the first human-rabbit hybrid using the nucleus transfer technique. The hybrid embryo developed in culture for a few days before it was destroyed and the stem cells harvested (47,48). The purpose of the research into creating hybrid embryos is to provide researchers with human stem cells for experimentation into cures for diseases such as cystic fibrosis, Alzheimer’s and Motor Neuron disease as human stem cell are difficult to obtain (50).

[[File:Rabbit clone.jpg|center|450 px|thumb|(A) Cloned rabbits (5 month old) from nuclear transfer technique. (B) The male rabbit whose fibroblasts were used as the nuclear donors. The cloned rabbits have almost identical genome to the male donor.]]

'''Stem Cells'''
[[File:HES.jpg|right|200 px|thumb|Human Embryonic Stem cell (hES).]]
[[File:Rabbit knee.jpg|right|200 px|thumb|Stem cell induced cartilage repair of knee in rabbit.]]

Stem cells are unspecialized cells which are able to continuously reproduce themselves and under appropriate conditions, differentiate into all the various specialized cells of the organism such as cardiac cells, neurons and blood cells (39,40). Adults have a small number of stem cells when compared to a developing embryo and the stem cell of an embryo more easily obtained (41). Human embryonic stem cells (hES) derived from the inner mass of the preimplantation blastocyst have the potential to differentiate into all cell types in the human body and thus are valued by researchers (50). However, due to ethical and political issues, the obtaining and experimentation on human embryonic stem cells is difficult and alternate means are needed as stem cell provides potentially new treatments for a range of diseases (54).

Rabbits can be used both in the obtaining of stem cell for experimentation and also as recipients of stem cells to cure diseases. The human-rabbit hybrid embryo provides a method of obtaining stem cells for experimentation and these stem cells possess many similar properties to human stem cells, including expression of surface markers, special growth requirements, capabilities of self renewal, formation of embryonic body and differentiation into cells of all three germ layers (53).

Stem cell experimentation on rabbits also focuses on transplanting stem cell into rabbits to treat specific diseases. A study at Zhejiang University where a research team transplanted human mesenchymal stem cell into New Zealand white rabbits with myocardial infarction recoded regeneration of vascular structure and improvement in cardiac function. The research team noted the potential of stem cells in differentiating into specialized cardiac cells when subjected to the specific conditions of the rabbit heart (52).

Another study at Hallym University tested the effectiveness of transplanting mesenchymal stem cells from New Zealand white rabbits into damaged cartilage in the knees of other New Zealand white rabbits. In the experiment, mesenchymal stem cells were obtained from the rabbit bone marrow and injected into the knees of other rabbits that had cartilage in their knees surgically damaged. The research team were able to conclude notable cartilage recovery in the rabbits with the mesenchymal stem cell injection and the potential of mesenchymal stem cells to differentiate into fibroblasts, adipoblasts, osteoblasts and chondroblasts (51,53).

The findings in stem cell experimentation with in rabbits yielded positive results and potentially opens a new field of research in the use of stem cell to treat a range of diseases in humans.

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# Li, S, & Chen X (2006). Rabbits generated from fibroblasts through nuclear transfer . Society for Reproduction and Fertility, 131. Retrieved from [http://www.reproduction-online.org/cgi/reprint/131/6/1085]
# Minger, S (2007). Interspecies SCNT derived human embryos. Regenerative Medicine, 2(2), Retrieved from [http://www.futuremedicine.com]
# Koga, H, Shimaya, M, & Muneta, T (2008). Local adherent technique for transplanting mesenchymal stem cells as a potential treatment of cartilage defect. Arthritis Research & Therapy, 10(4), Retrieved from [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2575632]
# Wang, J, Li, C, & Sun, Y (2005). Human bone marrow-derived mesenchymal stem cells transplanted into damaged rabbit heart to improve heart function. Journal of Zhejiang University Science, 6(4), Retrieved from [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1389731]
# Chen, Y, Liu, A, & Mao, W (2003). Embryonic stem cells generated by nuclear transfer of human somatic nuclei into rabbit oocytes. Cell Research , 13(4), Retrieved from [http://www.nature.com]
# Bethesda (2009, September 23). Stem Cell Information. Retrieved from [http://stemcells.nih.gov]
# Cibelli, J. B. (2002). Principles of cloning Amsterdam. Academic Press
# European rabbit (oryctolagus cuniculus) Retrieved 9/21/2009, 2009, from http://www.feral.org.au/content/species/rabbit.cfm
# Warner, S. (2003). Inositol transport in preimplantation rabbit embryos: Effects of embryo stage, sodium, osmolality and metabolic inhibitors Reproduction, 125(4), 479-493.
# Derelanko, M. J. (2008). The toxicologist's pocket handbook, second edition Informa HealthCare
# Beaudoin, S., Barbet, P., & Bargy, F. (2003). Developmental stages in the rabbit embryo: Guidelines to choose an appropriate experimental model Fetal Diagnosis and Therapy, 18(6), 422-427.

==Glossary==

Anesthetic - A drug that causes temporary loss of bodily sensations

Aplasia - The absence or defective development of a tissue or organ

Blastocyst - A stage of embryo development that occurs about five days after fertilisation when the embryo contains quite a few cells

Caudal - Situated towards the inferior or posterior end of the body

Cephalic - Relating to the head

Cerebral Aqueduct - A canal filled with cerebrospinal fluid within the midbrain

Cerebral Cortex - The layer of unmyelinated neurons (the grey matter) forming the cortex of the cerebrum of the brain

Cerebro Spinal Fluid (CSF) - A watery fluid which flows in the cavities within the brain and around the surface of the brain and spinal cord

Chromosome - Microscopic carriers of genetic material, composed of deoxyribonucleic acid (DNA) and proteins and appearing as rods under a microscope

Cisterna Magna - is one of three principal openings in the subarachnoid space between the arachnoid and pia mater layers of the meninges surrounding the brain

Diploid - A full set of genetic material, consisting of paired chromosomes one chromosome from each parental set

Dorsal - Position towards the back

Fontanel - Membranous gap between the bones of the cranium in an infant or fetus

Genome - All genetic information, the entire genetic complement and all of the hereditary material possessed by an organism. Made up of both chromosomal genome (inside the nucleus of the cell in the familiar form of chromosomes) and mitochondrial genome (outside the nucleus in the cytoplasm of the cell, usually in the form of one round chromosome (the mitochondrial chromosome))

Genotype - The genetic makeup of an organism

Glucocorticoids - A class of steroid hormones that bind to the glucocorticoid receptor (GR), which is present in almost every vertebrate

Haploid - A single set of chromosomes (half the full set of genetic material)

Laparotomy- Surgical incision into the abdominal wall; often done to examine abdominal organs

Ligases - Group of enzymes that catalyze the binding of two molecules

Oocyte - A female gametocyte that develops into an ovum after two meiotic divisions

Phenotype - The observable traits or characteristics of an organism, for example hair color, weight, or the presence or absence of a disease.

Pronuclear - Haploid nucleus before fusion of nuclei in fertilisation

Restriction Endonucleases - Enzymes that recognize and cleave specific DNA sequences, generating either blunt or single-stranded (sticky) ends

Retina - The thin layer of cells at the back of the eyeball where light is converted into neural signals sent to the brain

Rostral - Situated toward the oral and nasal region

Somite - Blocks of mesoderm on either side of the notochord and neural tube during development of the vertebrate embryo. Develop into muscles and vertebrae

Stenosis - Abnormal narrowing of a bodily canal or passageway

Weaning - Young become accustom to nourishment other than suckling

==Links to Research Laboratories and Researchers==

1) Transgenic lab: [http://www.dnavision.be/index.php]

Involved in development of transgenic organisms, DNA construction and phenotype analysis.

2) World Rabbit Science Association: (WRSA) [http://world-rabbit-science.com]

International Association where researchers exchange knowledge and encourage teaching, scientific research, practical experimentation, the collection and publication of statistics and documents relating to the rabbit. Even have their own journal called “World Rabbit Science”

Website provides contact with researchers, professors and veterinarians working with rabbits.

Example: Dr. Myriam Kaplan-Pasternak, Doctorate Veterinary Medicine, University of California, myriamsemail@gmail.com

3) American Veterinary Medical Association [http://www.avma.org]

The American Veterinary Medical Association (AVMA), established in 1863, is a not-for-profit association representing more than 78,000 veterinarians working in private and corporate practice, government, industry, academia, and uniformed services. Excellent website into animal research and has a range of veterinary journals.

{{Template:Projects09}}
[[Category:Rabbit]]
[[File:Example.jpg]]

File:Sizeswithscale.JPG

2009-10-14T12:37:17Z

Z3185685: Relative sizes of rabbit embryos. Adapted from Warner, S. (2003). Inositol transport in preimplantation rabbit embryos: Effects of embryo stage, sodium, osmolality and metabolic inhibitors Reproduction, 125(4), 479 <last_page> 493.

Relative sizes of rabbit embryos. Adapted from Warner, S. (2003). Inositol transport in preimplantation rabbit embryos: Effects of embryo stage, sodium, osmolality and metabolic inhibitors Reproduction, 125(4), 479 <last_page> 493.

2009 Group Project 1

2009-10-14T12:24:06Z

Z3185685:

[[File:Rabbits.png|right|400 px]]

== '''THE RABBIT (ORYCTOLAGUS CUNICULUS)''' ==

==Introduction==

[[File:Isidro_Martinez.jpg‎|left|175 px]]

Several characteristics of the rabbit make it an excellent model for study. This will be further explored in "The History of Model Use" section of this page. Many studies have resulted in the development and improvement of various micro-manipulation techniques such as the production of transgenic rabbits. Unlike many other species such as the chick or rat, relatively little is known about the development of a rabbit. Nevertheless, it is still an appropriate animal model as the results from many experiments are significant to that of other mammals, including humans. (55)

A rabbits potential for reproduction is high, breeding from the early stages of 3 to 4 months of age. A mature female rabbit can be pregnant from 6 to 8 months in a year, producing up to 30 to 40 young in this time. (56)

==History of Model Use==

'''WHY are we using rabbits?'''

ADVANTAGES
*Provides repeatability of animal model studies
*Large enough for single samples
*Many stocks/strains as animal models
*Easily managed
*Quality of immunologic products
*Ease of reproductive control

DISADVANTAGES
*Most colonies are a storehouse of diseases
*Extremely variable to responses to general anesthetics

'''Brief timeline of rabbit embryo model use'''

*1672- de Graaf found the Graffian follicle.
*1890- Walter Heape succeeded first mammalian embryo transfer
*1906- FT Lewis discovered the development of the lymphatic system in rabbit embryos.
*1941- Dr. Pincus succeeded in keeping rabbit embryos developing in the test
*1968- Edwards and Gardner successfully performed the first known embryo biopsy on rabbit embryos

=== Regnier de Graaf (1641–1673) ===
[[image:Ovary_Graaf.jpg|thumb|250px|left|drawing of ovary]]
[[File:Regnier de Graaf.jpg|right]]

'''Discovery of the Graafian Follicles'''

In 1672 de Graaf published ''The Generative Organs of Women'', which was primarily a study of development in the rabbit. When de Graaf discovered large, round welling on the ovaries of rabbits, he assumed they were mammalian eggs. De Graaf also described the corpus luteum.

He summarised the previous works from anatomists, but unable to experience the amazing benefits made by microscopy.
But Antonie van Leeuwenhoek (A microbiologist, 1632 - 1723) argued that the structures now known as Graafian follicles could not be eggs. Haller suggested that the egg might be formed by the coagulation of the fluid within the Graafian follicle. De Graaf noted that the “egg” did not contain a tiny embryo, but he thought it did contain the “germ” of the future organism. (3)

=== Walter Heape (1855-1928) ===
'''First case of embryo transfer experiments'''

On 27 April 1890, Walter Heape (a professor and physician at the University of Cambridge, England) transferred rabbit embryos from one mother to another. (7) One rabbit mother became pregnant and delivered young from the transferred embryos. This was the first mammalian embryo transfer experiment to be successfully completed. His embryo transfer work in perspective as it relates to other contributions of this pioneer in reproductive biology.(7)

In 1891, Walter Heape had been conducting research on reproduction in numerous animal species. Working with two species of rabbits, he flushed embryos from the rabbit fallopian tubes of one breed (Angora) and placed them into the uterus of a recently mated Belgian hare. In the resulting litter, there were 4 Belgians and 2 Angoras. Heape proved that it was possible to take preimplantation embryos and transfer them to a gestational carrier without affecting their development.(7)

===Dr. Gregory Goodwin Pincus (1903-1967) ===

'''Contraceptive pill'''

Dr. Pincus began studying hormonal biology and steroidal hormones early in his career. His first breakthrough came when he was able to produce in vitro fertilization in rabbits (by using chemicals) in 1934. Throughout their hormonal contraceptive research Pincus, along with reproductive physiologist Min Chueh Chang, found out progesterone would act as an inhibitor to ovulation. They co-invented the combined oral contraceptive pill.[2][6]

===Genetic Diagnosis===
In 1968, Robert Edwards and David Gardner reported the successful sexing of rabbit blastocysts, setting the first steps towards PGD (Preimplantation Genetic Diagnosis). It was not until the 1980s that human IVF was fully developed, which coincided with the breakthrough of the highly sensitive polymerase chain reaction (PCR) technology. Handyside and collaborators' first successful attempts at testing were in October 1989 with the first births in 1990 though the preliminary experiments had been published some years earlier. In these first cases, PCR was used for sex determination for patients carrying X-linked diseases.(12)

==Timeline of Embryo Development==

The following is a timeline, adapted from Cibelli (2002), of the main events of preimplantation development in rabbits. The time is measured in hours post-mating and shows the embryo stage (cell number) in each time scale.

[[File:Morula1.JPG|right|200 px|thumb|A day 2 early morula]]

'''12-14 hours:''' Oocyte; Fertilization

'''18-20 hours:''' Zygote; Pronuclear formation

'''24-26 hours:''' Two cell

'''30-32 hours:''' Four cell

'''38-40 hours:''' Eight cell; Maternal-zygotic transition

'''46-48 hours:''' Sixteen cell

'''54-56 hours:''' Morula (32 cell); Compaction and transport to uterus

'''64-66 hours:''' Compact morula (64 cell); Morula-blastocyst transition

'''76-78 hours:''' Early blastocyst (128 cell)

'''84-86 hours:''' Expanded blastocyst (256 cell); Blastocoels expansion

'''94-96 hours:''' Hatched blastocyst (512 cell); Hatching

The following shows a diagrammatic representation of the relative sizes of rabbit embryos. The sizes do not include the embryonic coverings such as the zona pellucida and mucin coat. This diagram has been adapted from Warner (2003).

[[File:Sizes.JPG]]

The following timelines show a comparison of the developmental stages between human and rabbit embryos. They have been adapted from Derelanko (2008). "The similarities of this developmental pattern in humans and rabbits, suggests that the same growth increment is required to achieve the same stage. The main difference observed between human rabbit gestational duration is due to the fetal growth phase. The reason for this may be due to birth weight, lifetime and the neural complexity of the species." (59)

[[File:Timeline_rabbit.JPG]]

The following timelines have been adapted from a study carried out by Beaudoin et al. on the development of rabbit embryos.

==='''Body Form'''===

'''8.5 days''': Embryo thickens. First somites appear. Rostral neuropore closes. Caudal neuropore remains open

'''9.5 days''': Dorsal curvature begins. Cardiac mass bulges under cephalic pole.

'''10.5 - 13.5 days''': Dorsal curvature increases. Body thickens. Softening of the cephalic domination straightens the embryo.

'''17.5 days''': Neck becomes visible.

==='''Limb Development'''===

''' 9.5 days''': Rostral limb bud appears

'''10.5 days''': Caudal limb bud appears

'''12.5 days''': Hand plate becomes present. Limbs become disposed.

'''13.5 days''': Foot plate and finger rays become visible.

'''14.5 days''': Rostral and caudal limbs become parallel.

'''15.5 days''': Elbow appears.

'''16.5 days''': Fingers start to elongate.

'''17.5 days''': Knee becomes visible

'''19.5 days''': Hands and feet merge on the midline. Three segments of limbs become distinguished.

==='''Abdominal Wall Development'''===

'''9.5 days''': Abdominal wall is limited to the embryonic pedicle under the cardiac mass.

'''13.5 days''': First intestinal loops appear in the umbilical cord.

'''14.5 days – 17.5''': Rapid intestinal development in the cord.

'''15.5 days''': Abdominal vesicles can be observed.

'''16.5 days''': Cecal bud becomes present outside the abdomen

'''18.5 days''': Bowel returns to the abdominal cavity and umbilical ring closes.

==='''Cephalic Development'''===

'''9.5 days''': One cerebral vesicle can be seen. Pharyngeal arches as optic vesicle are present.

'''10.5 days''': Three arches are distinguished in the cephalic pole.

'''11.5 days''': Three cerebral vesicles present. Optic plate is distinguished.

'''12.5 days''': Face develops nasal, maxillar and mandibular buds. Lens vesicle is closed. Five cerebral vesicles exist.

'''14.5 days''': The ear becomes refined. Face can be distinguished from the brow.

'''18.5 days''': Eyelid appears, covering the eyes.

==Staging==

The following stages have been adapted from Beaudoin et al. (2003). Table 1 represents at each age its corresponding stage defined by the Carnegie classification

{| class="wikitable" style="text-align:center; width: 800px; height:1000px" border="1"
|+'''Table 1. Rabbit developmental stages using Carnegie classification'''

|- style="height:50px"
! '''Stage''' !! '''Days''' !! '''Event''' !! '''Image'''
|- style="width:200px"
! width="50" | 10
| width="50" | 8.5 || First somites appear, rostral neuropore closes
|- style="height:75px"
! 12
| 9.5 || Rostral limb bud, embryonic pedicle, caudal neuropore closes, one cerebral vesicle, pharyngeal arches, completion of optic vesicle
| [[file: 9.5new.JPG|100px]]
|- style="height:75px"
! 13
| 10.5 || Dosral C-shaped curvature, caudal limb bud, prominent cardiac swelling, four pharyngeal arches
| [[file: 10.5new.JPG|100px]]
|- style="height:75px"
! 14
| 11.5 || Three cerebral vesicles, optic plate, mesonephric ridge
|- style="height:75px"
! 15
| 12.5 || Hand plate, wheel ray limbs, lens vesicle closes, five cerebral vesicles, facial buds, vertebrae
| [[file: 12.5new.JPG|100px]]
|- style="height:75px"
! 16
| 13.5 || Foot plate, finger rays, prominent liver, intestinal loops, auricular hillocks
| [[file: 13.5new.JPG|100px]]
|- style="height:100px"
! 19
| 14.5 || Cuboidal body, trunk straightens, parallel limbs, toe rays, modeled face, visible auricle
| [[file: 14.5new.JPG|100px]]
|- style="height:75px"
! 20
| 15.5 || Elbow, fingers elongate, notches between toe rays
| [[file: 15.5new.JPG|100px]]
|- style="height:75px"
! 21-22
| 16.5 || Toes free, cecal bud in intestinal hernia
| [[file: 16.5new.JPG|100px]]
|- style="height:75px"
! 22-23
| 17.5 || Knee, neck, eyelids
| [[file: 17.5new.JPG|100px]]
|- style="height:75px"
! 23
| 18.5 || Hands and feet join at the midline, closure of abdominal wall, eyelids cover eyes
| [[file: 18.5new.JPG|100px]]
|-
| colspan="4" align="center"| Following this stage fetal appearance is completed, organogenesis is achieved
|}

==Genetics==

===Sequencing===
The National Human Genome Research Institute selected the European rabbit (Oryctolagus cuniculus) for whole genome sequencing to enhance their understanding of the human genome and use it experimentally for an animal model for human disease. (8)

The rabbit has been sequenced twice by The Broad Institute as part of the mammalian genome project. It is now currently undergoing 7 more sequencing projects. Its sequencing is made by the Whole Genome Shotgun (WGS) and assembly method. (9) This is when genomic DNA is sheared into small pieces of approximately 2000 base pairs which are then cloned into plasmids and sequenced on both strands. Once the contig fragments are read, realigned and reassembled by computer algorithms, it will give the overall sequence. (10) (11) The image below shows diagramatically how the two types of sequencing are different. The same techniques are used for sequencing the human genome (in 2003). [A contig is a set of overlapping DNA segments, derived from a single source of genetic material, from which the complete sequence may be deduced.

The whole genome shotgun (WGS) has serious gaps, yet the information has already proven useful for immunological as well as in silico studies. Deeper 7x coverage started in September 2007. The NCBI Rabbit Genome Resources site has links to searches for genes in the assemblies of the 2x WGS sequence at Ensembl and UCSC.(12) [http://www.broadinstitute.org/models/europeanrabbit/ Rabbit Genome Project]

[[File:WGS_sequencing.gif‎|center|800 px]]

===Genome===
The Rabbit genome was published by two groups (9)
# Lindblad-Toh,K., Chang,J.L., Gnerre,S., Clamp,M. and Lander,E.S. published their admission of 84024 bases on May 5th 2005 to The Broad Institute (USA) by shotgun sequencing
# Di Palma,F., Heiman,D., Young,S., Gnerre,S., Johnson,J., Lander,E.S. and Lindblad-Toh,K. published their admission of 84024 bases on August 3rd 2009 to The Broad Institute (USA) by shotgun sequencing.
The rabbit's genome is sequenced and on display in the Nucleotide Data Bank. It is too long to produce here. A link to the data bank is provided: [http://www.ncbi.nlm.nih.gov/nuccore/256946799/ Rabbit Genome from the Nucleotide Data Bank]

[[File:8cellembryo.jpg|thumb|Individual mitochondria (arrowheads) of an 8cell Rabbit embryo]]

The rabbit genome was sequenced in 2005 by Ensembl and managed to produce: (13)
* 2,076,044,328 supercontigs (ordered Contigs with gaps)
* 495 Known protein-coding genes
* 11,357 Projected protein-coding genes
* 2,343 RNA genes
* 212,581 Gene exons
* 20,311 Gene transcripts

For further research the taxonomy ID number for the Rabbit is: 9986 [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=9986&lvl=3&lin=f&keep=1&srchmode=1&unlock/ Taxonomy Data]

===Mitochondrial Genome===
The mitochondiral genome (mtDNA) of the rabbit was sequenced on November 14th 2006 with 17245 base pairs/nucleotides in circular form. Apparently the "length is not absolute due to the presence of different numbers of repeated motifs in the control region".
PMID 9653643

The image to the right shows the mitochondria during cell division and multiplication in embryo development.

=== Chromosomes ===
Over the years there have been various data suggesting the diploid chromosomal number for the rabbit may range from 22-42. However through recent research and an abundance of trials suggest that the rabbit does indeed have 22 different chromosome pairs existing in each cell of the rabbit. (16)(17) The sex chromosomes of the rabbit are of X-Y type convincingly (17). In a study in Bombay it confirmed that a rabbit has 2n = 44 chromosomes. There were 21 pairs of autosomes, out of which 1 to 6 were metacentric, 7 to 11 submetacentric, 12 to 17 subtelocentric and 18 to 21 acrocentric, plus the sex chromosomes. The image to the left shows a female rabbit with no chromosomal abnormalities. (19)

'''Comparison to human chromosome:'''

Rabbit chromosomes 12, 19 and X were found to be completely homologous to human chromosomes 6, 17 and X, respectively. All other human chromosomes were homologous to two or sometimes three rabbit chromosomes. (14) Chromosome 12 was shorter than chromosomes 13 and 14. (15) The image below illustrates the human chromosome (2n = 46).

[[File:Drawn chromosome.jpg|left|400 px]]

[[File:Karyotypehuman.gif|right|500 px]]

'''Abnormalities'''

These are generally more apparent during early embryo development in blastocysts from delayed fertilization. Some examples of abnormal development include cases of: (18)
* hypoploidy; 1 chromosome missing from a pair (2n = 43),
* double hypoploidy; 2 chromosomes missing from 2 different pairs (2n = 42),
* mosaicism (different chromosomal makeup in some cells).

Another study also found these abnormalities as well as: (19)
* autosomal trisomy (3 autosomes per pair),
* triploidy (extra set of chromsomes),
* mixoploidy (unequal number of chromosome sets in adjacent cells), and
* short arm deletion (deletion of parts of chromosomes).

A specific abnormality occurring in rabbits is the x-linked tremor. There is a mutation in exon 2 of the prteolipid-protein (PLP 1) gene, corresponding to the end of the first potential transmembrane domain of the protein. This disorder affects myelination of the central nervous system. OMIA ID:12 [http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=full_report&list_uids=100009169&log$=omiamaingene| Gene:100009169]

==Abnormal Development==

Abnormal embryological development is a vast field of study that has been the subject of recent research papers. Our investigation of abnormal development in rabbit embryology will focus on abnormalities commonly found in both rabbit and human embryos. We will explore the nature of these abnormalities in both humans and rabbits.

[[File:Normal v Abnormal.jpg|right|300 px|thumb|Brain MRI of patient with Hydrocephalus (left) compared to a normal brain (right). An obvious increase in ventricular size and a significant decrease in brain size is present.]]
[[File:Ventricle_Expansion.jpg|right|300 px|thumb|CSF accumulation in ventricles of brain increasing intracranial pressure.The pressure from the expanding ventricles force the brain and skull to grow outwards abnormally.]]

'''Hydrocephalus'''

Annually, one in every 1000 children born in Australia have hydrocephalus. Hydrocephalus occurs when excessive cerebrospinal fluid (CSF) accumulates in the brain and can result in severe disability and even death because the disorder can result in complete or near complete destruction of the cerebral cortex (22).

Children born with hydrocephalus typically exhibit abnormally large head circumference and bulging cranial fontanels as a result of increased intracranial pressure on the brain from the accumulating CSF (22,23). As CSF accumulates in the ventricles and CSF compartments of the brain, it expands forcing the brain to grow outward. The outward growing brain places pressure on the skull which in turn also grows outwards giving rise to an abnormally large head circumference and bulging cranial fontanels (22,24). It is generally acknowledged that children with hydrocephalus have mental retardation, often to the degree of being “vegetative” (24).

The serious consequences of this disease mean that much research is necessary to unearth methods of prevention and effective treatment. One of the modes of studying hydrocephalus is to use the rabbit experimental model where hydrocephalus can be induced in rabbit embryo’s. The injection of silicone oil into the cisterna magna of the brain is one way of inducing hydrocephalus in the rabbit embryo. The silicone oil obstructs the normal flow of CSF resulting in CSF accumulation in the brain leading to hydrocephalus (25). Another method of inducing hydrocephalus in rabbit embryo’s is by intentional vitamin A deprivation of pregnant dams. The vitamin A deficiency results in raised intracranial CSF pressure and aqueduct stenosis causing poor circulation of CSF leading to hydrocephalus (26,27). Although the exact function of vitamin A on brain development and CSF regulation is not fully understood, it is clear that Vitamin A has an important role in brain development and its normal functioning (27).
[[File:Rabbithhdrocephalus.jpg|center|300 px|thumb|Young rabbit with hydrocephalus caused by Vitamin A deficiency. Note the abnormally shaped cranium inflamed in appearance.]]

[[File:SpinabifidaMeningocele1.jpg|right|300 px|thumb|Spina Bifida Meningocele has characteristic damage to the meninges of the spinal cord which are pushed out through an opening in the vertebrae as a cyst filled with CSF.]]
[[File:SpinaBifidaMyelomeningocele.jpg|right|300 px|thumb|Spina Bifida Myelomeningocele is the most severe form of spinabifida where the damaged spinal cord protrudes out with damaged meninges as a cyst filled with CSF.]]
[[File:SpinaBifidaOcculta1.jpg|right|300 px|thumb|Spina Bifida Occulta is the least severe as the spinal cord and meninges are undamaged.]]

'''Spina Bifida'''

In Australia, the risk of spina bifida is 1 in every 500 pregnancies. Spina bifida is a type of neural tube defect where vertebrae (which normally cover and protect the spinal cord) are not completely formed but are divided resulting in the defective spinal cord and its coverings to protrude through the opening (28,29).

There are three main types of Spina Bifida differentiated by their characteristic features:

1)Spina Bifida Meningocele characterized by normal spinal cord, divided outer vertebrae and meninges surrounding the spinal cord protruding from the divided vertebrae as a cyst (1,28).

2)Spina Bifida Myelomeningocele characterized by split outer vertebrae with spinal cord and its meninges protruding from the divided vertebrae as a cyst. Commonly found at lumbar vertebral level (1,28,29).

3)Spina Bifida Occulta characterized unfused vertebral arches and exposed vertebral canal. Spinal cord and its meninges still located in vertebral canal (1,28).

All forms of spina bifida are potentially fatal and in those where the spinal cord is damaged severe consequence arise including and paralysis and loss of sensation at and below the level of damage spinal cord damage (29,33). There is a lot of Spina bifida research using rabbit models to test the effective methods of correcting spina bifida. The occurrence of natural spina bifida in rabbits is rare and for experimental purposes it can be surgically created in rabbit fetuses during gestation (31,32). The process involves aesthetical sedation of the maternal rabbit at day 22 of gestation; a midline laparotomy performed and the desired type of spina bifida lesion created on the exposed fetus using forceps. Different methods for correcting spina bifida can then be tested and its effectiveness analysed (30,33,34).
[[File:Rabbitspinabifida1.jpg|center|350 px|thumb|Rabbit newborn with Spina Bifida. Note the unfused, divided vertebrae and exposed spinal cord.]]

'''Brachydactylia & Acheiropodia'''

[[File:Malformation1.jpg|right|150 px|thumb|Acheiropodia in rabbit characterized by amputations of the limbs and extremities.]]

[[File:Rabbitmalformation3.jpg|left|150 px|thumb|X-Ray study of rabbit limbs with malformed phalanges due to Brachydactylia.]]

Brachydactylia and Acheiropodia are genetic disorders characterized by skeletal malformation of the hands and feet (36,36). In Brachydactylia, the malformations commonly involve abnormal shortening of fingers and toes due to poorly formed or absent bones (35). Acheiropodia is characterized by more severe skeletal malformations including bilateral amputations of the distal upper and lower extremities as well as aplasia of the hands and feet. Although it is not fatal, the individual endures a very difficult life without hands and feet (37).

The inheritance mechanism of this diseases can has been studied through experiment using rabbits. Rabbits with abnormal genes coding for Brachydactylia and Acheiropodia are selected and bred to produce offspring with the disease (36). Brachydactylia and Acheiropodia are autosomal recessive disorders which means that two copies of an abnormal gene must be present in the affected individual in order for the disease to develop. Thus, each parent passes an abnormal gene to the offspring (35,36). The process of the malformation progresses from genotype to phenotype; small deletions on the chromosomes produce abnormal genes, the abnormal genes are then passed down to the offspring, the offspring that inherits two of the abnormal genes is unable to code for the correct proteins and as a result, there is failure in normal development of limb extremities in the embryo phenotype (37,38).

==Current Embryology Research==

There is currently great excitement in research involving rabbits in the fields of transgenesis, cloning and stem cells. We shall explore research in these areas by discovering some of the techniques used and how they have been applied to the rabbit model.

[[File:Trans1.jpg|right|170 px]]
[[File:Trans2.jpg|right|170 px]]
[[File:Trans3.jpg|right|170 px]]
[[File:Trans4.jpg|right|170 px]]
[[File:Trans5.jpg|right|170 px]]

'''Transgenic rabbit'''

A transgenic organism is one whose genome also contains genes from another species (39). The aim of creating a transgenic organism is to obtain a favorable characteristic in the organism’s phenotype (41). This desired characteristic of phenotype is obtained by altering the organism’s normal genotype to include the gene from another species with the desired characteristic (39,40).

The production of a transgenic organism involves several steps summarized below:

1) The chromosome and the desired gene on it are identified in an organism (39).

2) The gene is isolated from its DNA strand. This involves “cutting” it out of its DNA strand using enzymes called restriction endonucleases. The restriction endonucleases cut DNA at specific site so the desired gene can be removed from the DNA strand. The cut ends are known as “sticky ends” (39,40).

3) Separate DNA sequences for regulation sometimes have to be added to ensure the gene will work (40).

4) The gene is then inserted with a promoter sequence into the fertilized egg cell of a new organism producing recombinant DNA (39,44). To do this, firstly the new organism’s cell DNA must first be cut and the desired gene incorporated into it. The same enzymes are used to cut the new organism’s cell DNA because the DNA stands from the two different organisms will form matching sticky ends that will be attracted to and connect with each other in a process is called “annealing” (39,40,44).

5) DNA ligases are sealing enzymes found in all living organisms that help make and repair DNA (39,40). The DNA ligases are added to the annealed DNA fragments to help strengthen the bonds of the new recombinant DNA. The recombinant DNA is now transferred into the new organism’s fertilized egg by microinjection (44).

6) As the embryo develops and the recombinant genetic code read, new proteins are synthesized which code for the new desired phenotype characteristic in the transgenic organism (39,40).

Transgenic rabbits can be created in the laboratory by gene microinjection into the fertilized rabbit oocyte (44). In April 2000, a transgenic rabbit named Alba was born containing a gene from a Pacific Northwest jellyfish. The gene which was injected into a fertilized albino rabbit oocyte allows the rabbit to synthesize the green fluorescent protein (GFP) that is characteristic of the Pacific Northwest jellyfish. When illuminated correctly, Alba glows a bright green (43,46).

Transgenic rabbits have important research purposes. Transgenic rabbits can be created to model retinal degeneration (44). Retinal degeneration is a common problem with aging and diseases such as diabetes, and frequently leads to complete blindness (42). A genetic retinal degeneration disease called retinitis pigmentosa (RP) is created in these rabbits by introducing the “Pro347Leu” mutation of the rhodopsin gene into fertilized rabbit eggs (43,44). As the rabbit grows, it develops the disease which becomes progressively worse (45).
The use of these transgenic rabbits ultimately leads to better understanding of the disease and more effective treatments (42). [[File:Transgenic rabbit.jpg|center|250 px|thumb|"Alba" A trangenic rabbit with a gene from a Pacific Northwest jellyfish that allows it to synthesize the green fluorescent protein (GFP) of the jellyfish.]]

[[File:Crabbit 1.jpg|right|170 px]]
[[File:Rabbit2.jpg|right|170 px]]
[[File:Rabbit3.jpg|right|170 px]]
[[File:Crabbit 4.jpg|right|170 px]]

'''Cloning'''

Cloning is a method of producing genetically identical organisms. The principle of cloning relies on “tricking” an egg cell to begin rapidly dividing into an embryo (39). In the normal fertilization process, two haploid sex cells unite to form a diploid zygote which begins rapidly dividing into an embryo (40). By replacing the haploid egg cell nucleus with a diploid somatic cell nucleus, the egg cell is tricked into thinking it is fertilized and hence begins rapidly dividing to form an embryo (39,40,41).

The process of cloning involves several steps summarized as the following using a rabbit example:

1) A somatic cell is obtained from a rabbit and the nucleus removed (39).

2) An egg cell is obtained from a donor rabbit and the nucleus of the egg cell removed using an enucleation needle. The cell is now called an enucleated egg cell (egg cell without a nucleus) (39,41).

3) The nucleus of the somatic cell is inserted into the enucleated egg cell (41).

4) The cell is now stimulated to divide by applying pulses of electric current (39).

5) The rapidly dividing cell develops in culture for a few days forming the early embryo (40,41).

6) The embryo is then implanted into the uterus of another rabbit similar to the egg cell donor. This rabbit is called the surrogate mother (40,41).

7) The embryo develops and the surrogate mother gives birth to a rabbit fetus with near identical genotype of the somatic cell donor (the small genomic difference is caused by the fetus obtaining mitochondrial DNA from the egg cell donor) (39,41).

The cloning of rabbits has been achieved by inserting the diploid nucleus of a rabbit fibroblast (the principal cells in connective tissue) into an enucleated oocyte (49). There is currently much focus on the creation of controversial but revolutionary interspecies hybrid embryos where the nucleus from a human somatic cells are implanted into an enucleated egg cell of another animal (50). The resulting embryo (known as a chimera) will be almost completely human genotype but will have genome from the other animal (48). In 2003, scientists at the Shanghai Second Medical University fused human cell with rabbit eggs creating the first human-rabbit hybrid using the nucleus transfer technique. The hybrid embryo developed in culture for a few days before it was destroyed and the stem cells harvested (47,48). The purpose of the research into creating hybrid embryos is to provide researchers with human stem cells for experimentation into cures for diseases such as cystic fibrosis, Alzheimer’s and Motor Neuron disease as human stem cell are difficult to obtain (50).

[[File:Rabbit clone.jpg|center|450 px|thumb|(A) Cloned rabbits (5 month old) from nuclear transfer technique. (B) The male rabbit whose fibroblasts were used as the nuclear donors. The cloned rabbits have almost identical genome to the male donor.]]

'''Stem Cells'''
[[File:HES.jpg|right|200 px|thumb|Human Embryonic Stem cell (hES).]]
[[File:Rabbit knee.jpg|right|200 px|thumb|Stem cell induced cartilage repair of knee in rabbit.]]

Stem cells are unspecialized cells which are able to continuously reproduce themselves and under appropriate conditions, differentiate into all the various specialized cells of the organism such as cardiac cells, neurons and blood cells (39,40). Adults have a small number of stem cells when compared to a developing embryo and the stem cell of an embryo more easily obtained (41). Human embryonic stem cells (hES) derived from the inner mass of the preimplantation blastocyst have the potential to differentiate into all cell types in the human body and thus are valued by researchers (50). However, due to ethical and political issues, the obtaining and experimentation on human embryonic stem cells is difficult and alternate means are needed as stem cell provides potentially new treatments for a range of diseases (54).

Rabbits can be used both in the obtaining of stem cell for experimentation and also as recipients of stem cells to cure diseases. The human-rabbit hybrid embryo provides a method of obtaining stem cells for experimentation and these stem cells possess many similar properties to human stem cells, including expression of surface markers, special growth requirements, capabilities of self renewal, formation of embryonic body and differentiation into cells of all three germ layers (53).

Stem cell experimentation on rabbits also focuses on transplanting stem cell into rabbits to treat specific diseases. A study at Zhejiang University where a research team transplanted human mesenchymal stem cell into New Zealand white rabbits with myocardial infarction recoded regeneration of vascular structure and improvement in cardiac function. The research team noted the potential of stem cells in differentiating into specialized cardiac cells when subjected to the specific conditions of the rabbit heart (52).

Another study at Hallym University tested the effectiveness of transplanting mesenchymal stem cells from New Zealand white rabbits into damaged cartilage in the knees of other New Zealand white rabbits. In the experiment, mesenchymal stem cells were obtained from the rabbit bone marrow and injected into the knees of other rabbits that had cartilage in their knees surgically damaged. The research team were able to conclude notable cartilage recovery in the rabbits with the mesenchymal stem cell injection and the potential of mesenchymal stem cells to differentiate into fibroblasts, adipoblasts, osteoblasts and chondroblasts (51,53).

The findings in stem cell experimentation with in rabbits yielded positive results and potentially opens a new field of research in the use of stem cell to treat a range of diseases in humans.

==References==

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# E.Horne Craigie, University of Toronto Press 1948, Bensley's Practical Anatomy of the Rabbit 8th Edition
# Ankum WM, Houtzager HL, Bleker OP (1996). "Reinier De Graaf (1641-1673) and the fallopian tube". Human Reproduction Update 2 (4): 365–9. doi:10.1093/humupd/2.4.365. PMID 9080233.
# Jocelyn HD, Setchell BP (December 1972). "Regnier de Graaf on the human reproductive organs. An annotated translation of Tractatus de Virorum Organis Generationi Inservientibus (1668) and De Mulierub Organis Generationi Inservientibus Tractatus Novus (1962)". Journal of Reproduction and Fertility. Supplement 17: 1–222.
# Jay, V. (2000). "A portrait in history. The legacy of Reinier de Graaf". Archives of Pathology & Laboratory Medicine 124(8): 1115–6.
# Lois N Magner. "A history of the Life Sciences" 3rd edition
# J. D. Biggers. (1991). Walter Heape, FRS: a pioneer in reproductive biology.Centenary of his embryo transfer experiments Laboratory of Human Reproduction and Reproductive Biology, and Department of Cellular and Molecular Physiology, Harvard Medical School, Boston, MA 02115, USA
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# The Broad Institute. (2008). ''Rabbit Genome Sequencing Project''. Retrieved only August 29, 2009, from [http://www.broadinstitute.org/models/europeanrabbit/ Rabbit Genome Sequencing Project]
# Campbell, M. A. (2002). ''Sequencing Whole Genomes: Hierarchical Shotgun Sequencing v. Shotgun Sequencing'' Retrieved August 31, 2009, from [http://www.bio.davidson.edu/courses/GENOMICS/method/shotgun.html/ Shotgun Sequencing - 1]
# Trivedi, B. (2000). ''Sequencing the Genome''. Retrieved September 4, 2009, from [http://www.genomenewsnetwork.org/articles/06_00/sequence_primer.shtml Shotgun Sequencing - 2]
# Mage, R. (2008). Rabbit genome sequencing update: genes of immunological interest found in the 2x genome assemblies, ENCODE, and the 7x trace archive. ''Journal of FASEB'' 22(Retrieved September 5, 2009, from [http://www.fasebj.org/cgi/content/meeting_abstract/22/2_MeetingAbstracts/559/ Rabbit Genome & its Immunological Interest]
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# Korstanje, R. et al. (1999) Complete homology maps of the rabbit (Oryctolagus cuniculus) and human by reciprocal chromosome painting. ''Cytogenetics and cell genetics'' ''86''(3-4), 317-322. Retrieved September 6, 2009, from [http://cat.inist.fr/?aModele=afficheN&cpsidt=1189693/ Complete homology maps of the rabbit Article] "PMID 10575232"
# Brunner, R., Knopp, A., Rudolph, W. (n.d). Rabbit chromosome analysis by image processing. ''Journal of Applied Rabbit Research''.
# DebMark Rabbit Education Resource (2006). ''Rabbit Genetics''. Retrieved September 6, 2009, from [http://www.debmark.com/rabbits/genetics.htm/ Rabbit Genetics]
# Painter, T. (2009) Studies in mammalian spermatogenesis VI. The chromosomes of the rabbit. ''Journal of Morphology''. ''43''(1): 1-43.
# Hofsaess, F., and Meacham, T. ( 1995) Chromosome abnormalities of early rabbit embryos. ''Journal of Experimental Zoology''. ''177'' (1): 9-11 [http://www3.interscience.wiley.com/journal/110490865/abstract/ Chromosome abnormalities]
# Martin-Deleon, P., Shaver, E., and Gammal, E. (1973) Chromosome abnormalities in rabbit blastocysts resulting from spermatozoa aged in the male tract. ''Fertility and Sterility''. ''24''(3):212-219.
# Patil, M. et al (2004) Chromosome analysis of domestic rabbit. ''The Journal of Bombay Veterinary College''. ''12'' (1 and 2)
#Biggers J.D (1991) Walter Heape FRS: a pioneer in reproductive biology. centenary of his embryo transfer experments.''Journals of reproduction and fertility''. ''93''(1)
# Stoodley, M (2006). Hydrocephalus. Prince of Wales Clinical School. Retrieved from [http://www.brainaustralia.org.au/AZ_of_Brain_Disorders/hydrocephalus]
# National Institute of Neurological Disorders and Stroke (2008, February). Hydrocephalus Fact Sheet. Retrieved from [http://www.ninds.nih.gov/disorders/hydrocephalus/detail_hydrocephalus.htm]
# Lewin, R (1999). Is Your Brain Really Necessary?. 24) Developmental Medicine & Child Neurology, 41. Retrieved from [http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=176431]
# Bigio, M.R, & Bruni J.E (1991). Silicone oil-induced hydrocephalus in the rabbit . Child's Nervous System, 7(2), Retrieved from [http://www.springerlink.com/content/b011477724837152/]
# Geelen, J.A (1974). A case of hydrocephalus and meningoencephalocele in a rabbit, caused by aqueductal malformation. Laboratory Animals, 8(2), Retrieved from [http://la.rsmjournals.com/cgi/content/abstract/8/2/167]
# LAMMINGX, G.E (1954). 27) Hydrocephalus in Young Rabbits Associated with Maternal Vitamin A Deficiency. British Journal of Nutrition, 8(2), Retrieved from [http://journals.cambridge.org/download.php?file=%2FBJN%2FBJN8_04%2FS0007114554000554a.pdf&code=10bb1dbc4a9e57a091f4e05f6aebbcf2]
# Carney, A (2008, February ). Spina bifida. Retrieved from [http://www.spinabifida.asn.au/]
# Better Health Channel (2008, October ). Spina bifida explained . Retrieved from [http://www.betterhealth.vic.gov.au/bhcv2/bhcarticles.nsf/pages/Spina_bifida_explained]
# Peeters, M.C, Viebahn, C, & Hekking, J.W (1998). Neurulation in the rabbit embryo . Anatomy and Embryology, 197(3), Retrieved from [http://www.springerlink.com/content/1efyteewgetjlwyg/]
# George, T.M, & Fuh E (2003). Review of Animal Models of Surgically Induced Spinal Neural Tube Defects: Implications for fetal surgery. Pediatric Neurosurgery , 39(2), Retrieved from [http://content.karger.com/produktedb/produkte.asp?typ=fulltext&file=PNE2003039002081]
# Pedreira, D.A, & Valente P.R (2002). A Different Technique to Create a 'Myelomeningocele-Like' Defect in the Fetal Rabbit. Fetal diagnosis and therapy, 17(6), Retrieved from [http://content.karger.com/ProdukteDB/produkte.asp?Doi=65388]
# Patten, B.M (1953). Embryological stages in the establishing of myeloschisis with spina bifida. The American journal of anatomy, 93(3), Retrieved from [http://deepblue.lib.umich.edu/handle/2027.42/49611]
# Pedreira, D.A, & Valente P.R (2003). Successful Fetal Surgery for the Repair of a 'Myelomeningocele-Like' Defect Created in the Fetal Rabbit. Fetal Diagnosis and Therapy, 18. Retrieved from [http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowPDF&ProduktNr=224239&Ausgabe=229041&ArtikelNr=69378]
# Lecklitner, M.L, & Douglas K.P (1986). Osteoscintigraphy and brachydactylia of the hand . European Journal of Nuclear Medicine and Molecular Imaging, 12(9), Retrieved from [http://www.springerlink.com/content/t82l77282x579102/]
# Greene, H.S, & Saxton J.A (1938). HEREDITARY BRACHYDACTYLIA AND ALLIED. ABNORMALITIES IN THE RABBIT. THE JOURNAL OF EXPERIMENTAL MEDICINE , 69. Retrieved from [http://jem.rupress.org/cgi/reprint/69/2/301.pdf]
# P. Ianakiev, M. van Baren, M. Daly, S. Toledo, M. Cavalcanti, J. Neto, E. Silveira, A. Freire-Maia, P. Heutink, M. Kilpatrick. Acheiropodia Is Caused by a Genomic Deletion in C7orf2, the Human Orthologue of the Lmbr1 Gene. The American Journal of Human Genetics, 68. Retrieved from [http://linkinghub.elsevier.com/retrieve/pii/S0002929707624707]
# Walbaum, R, Hazard, C, & Cordier, R (1976). Brachydactylia with symphalangism, probably autosomal recessive . Human Genetics, 33(2), Retrieved from [http://www.springerlink.com/content/m630p6880661486n]
# Campbell, N.A, & Reece, J.B (2002). Biology 6th Edition. USA: Benjamin Cummings.
# Solomon, E.P, Berg, L.R, & Martin, D.W (2002). Biology 6th Edition. USA: Thompson Learning.
# Glanville, A.R (2008). Scientifica. NSW, Australia: Millennium House.
# Lund, R.D (2008). Saving Vision with Skin Cells. Retrieved from [http://www.blindness.org]
# Jones, B.W, & Marc R.E (2008). Computational Molecular Phenotyping and Excitation Mapping in the P347L. Retinal Degeneration , (2986), Retrieved from [http://prometheus.med.utah.edu/]
# Kondo, M, Sakai, T, & Ueno, S (2009). Generation of a Transgenic Rabbit Model of Retinal Degeneration. Investigative Ophthalmology and Visual Science, 50. Retrieved from [http://www.iovs.org/cgi]
# Punzo, C, Chen, B, & Roesch, K (2009). PHOTORECEPTOR DEATH IN MOUSE MODELS OF RETINITIS PIGMENTOSA. Retrieved from [http://genepath.med.harvard.edu]
# Zimmer, M (2008). Alba. Retrieved from [http://www.conncoll.edu/ccacad/zimmer/GFP-ww/cooluses8.html]
# Scott, C (2006, May 1). Chimeras in the crosshairs. Nature Biotechnology , 24, Retrieved from [http://www.nature.com/nbt/journal/v24/n5/abs/nbt0506-487.html]
# Mott, M (2005, January 25). Animal-Human Hybrids Spark Controversy. National Geographic News, Retrieved from [http://theyfly.com/PDF/Nat.%20Geo.%20Animal-Human%20Hybrids.pdf]
# Li, S, & Chen X (2006). Rabbits generated from fibroblasts through nuclear transfer . Society for Reproduction and Fertility, 131. Retrieved from [http://www.reproduction-online.org/cgi/reprint/131/6/1085]
# Minger, S (2007). Interspecies SCNT derived human embryos. Regenerative Medicine, 2(2), Retrieved from [http://www.futuremedicine.com]
# Koga, H, Shimaya, M, & Muneta, T (2008). Local adherent technique for transplanting mesenchymal stem cells as a potential treatment of cartilage defect. Arthritis Research & Therapy, 10(4), Retrieved from [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2575632]
# Wang, J, Li, C, & Sun, Y (2005). Human bone marrow-derived mesenchymal stem cells transplanted into damaged rabbit heart to improve heart function. Journal of Zhejiang University Science, 6(4), Retrieved from [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1389731]
# Chen, Y, Liu, A, & Mao, W (2003). Embryonic stem cells generated by nuclear transfer of human somatic nuclei into rabbit oocytes. Cell Research , 13(4), Retrieved from [http://www.nature.com]
# Bethesda (2009, September 23). Stem Cell Information. Retrieved from [http://stemcells.nih.gov]
# Cibelli, J. B. (2002). Principles of cloning Amsterdam. Academic Press
# European rabbit (oryctolagus cuniculus) Retrieved 9/21/2009, 2009, from http://www.feral.org.au/content/species/rabbit.cfm
# Warner, S. (2003). Inositol transport in preimplantation rabbit embryos: Effects of embryo stage, sodium, osmolality and metabolic inhibitors Reproduction, 125(4), 479-493.
# Derelanko, M. J. (2008). The toxicologist's pocket handbook, second edition Informa HealthCare
# Beaudoin, S., Barbet, P., & Bargy, F. (2003). Developmental stages in the rabbit embryo: Guidelines to choose an appropriate experimental model Fetal Diagnosis and Therapy, 18(6), 422-427.

==Glossary==

Anesthetic - A drug that causes temporary loss of bodily sensations

Aplasia - The absence or defective development of a tissue or organ

Blastocyst - A stage of embryo development that occurs about five days after fertilisation when the embryo contains quite a few cells

Caudal - Situated towards the inferior or posterior end of the body

Cephalic - Relating to the head

Cerebral Aqueduct - A canal filled with cerebrospinal fluid within the midbrain

Cerebral Cortex - The layer of unmyelinated neurons (the grey matter) forming the cortex of the cerebrum of the brain

Cerebro Spinal Fluid (CSF) - A watery fluid which flows in the cavities within the brain and around the surface of the brain and spinal cord

Chromosome - Microscopic carriers of genetic material, composed of deoxyribonucleic acid (DNA) and proteins and appearing as rods under a microscope

Cisterna Magna - is one of three principal openings in the subarachnoid space between the arachnoid and pia mater layers of the meninges surrounding the brain

Diploid - A full set of genetic material, consisting of paired chromosomes one chromosome from each parental set

Dorsal - Position towards the back

Fontanel - Membranous gap between the bones of the cranium in an infant or fetus

Genome - All genetic information, the entire genetic complement and all of the hereditary material possessed by an organism. Made up of both chromosomal genome (inside the nucleus of the cell in the familiar form of chromosomes) and mitochondrial genome (outside the nucleus in the cytoplasm of the cell, usually in the form of one round chromosome (the mitochondrial chromosome))

Genotype - The genetic makeup of an organism

Glucocorticoids - A class of steroid hormones that bind to the glucocorticoid receptor (GR), which is present in almost every vertebrate

Haploid - A single set of chromosomes (half the full set of genetic material)

Laparotomy- Surgical incision into the abdominal wall; often done to examine abdominal organs

Ligases - Group of enzymes that catalyze the binding of two molecules

Oocyte - A female gametocyte that develops into an ovum after two meiotic divisions

Phenotype - The observable traits or characteristics of an organism, for example hair color, weight, or the presence or absence of a disease.

Pronuclear - Haploid nucleus before fusion of nuclei in fertilisation

Restriction Endonucleases - Enzymes that recognize and cleave specific DNA sequences, generating either blunt or single-stranded (sticky) ends

Retina - The thin layer of cells at the back of the eyeball where light is converted into neural signals sent to the brain

Rostral - Situated toward the oral and nasal region

Somite - Blocks of mesoderm on either side of the notochord and neural tube during development of the vertebrate embryo. Develop into muscles and vertebrae

Stenosis - Abnormal narrowing of a bodily canal or passageway

Weaning - Young become accustom to nourishment other than suckling

==Links to Research Laboratories and Researchers==

1) Transgenic lab: [http://www.dnavision.be/index.php]

Involved in development of transgenic organisms, DNA construction and phenotype analysis.

2) World Rabbit Science Association: (WRSA) [http://world-rabbit-science.com]

International Association where researchers exchange knowledge and encourage teaching, scientific research, practical experimentation, the collection and publication of statistics and documents relating to the rabbit. Even have their own journal called “World Rabbit Science”

Website provides contact with researchers, professors and veterinarians working with rabbits.

Example: Dr. Myriam Kaplan-Pasternak, Doctorate Veterinary Medicine, University of California, myriamsemail@gmail.com

3) American Veterinary Medical Association [http://www.avma.org]

The American Veterinary Medical Association (AVMA), established in 1863, is a not-for-profit association representing more than 78,000 veterinarians working in private and corporate practice, government, industry, academia, and uniformed services. Excellent website into animal research and has a range of veterinary journals.

{{Template:Projects09}}
[[Category:Rabbit]]
[[File:Example.jpg]]

2009 Group Project 1

2009-10-14T12:22:43Z

Z3185685: /* Current Embryology Research */

[[File:Rabbits.png|right|400 px]]

== '''THE RABBIT (ORYCTOLAGUS CUNICULUS)''' ==

==Introduction==

[[File:Isidro_Martinez.jpg‎|left|175 px]]

Several characteristics of the rabbit make it an excellent model for study. This will be further explored in "The History of Model Use" section of this page. Many studies have resulted in the development and improvement of various micro-manipulation techniques such as the production of transgenic rabbits. Unlike many other species such as the chick or rat, relatively little is known about the development of a rabbit. Nevertheless, it is still an appropriate animal model as the results from many experiments are significant to that of other mammals, including humans. (55)

A rabbits potential for reproduction is high, breeding from the early stages of 3 to 4 months of age. A mature female rabbit can be pregnant from 6 to 8 months in a year, producing up to 30 to 40 young in this time. (56)

==History of Model Use==

'''WHY are we using rabbits?'''

ADVANTAGES
*Provides repeatability of animal model studies
*Large enough for single samples
*Many stocks/strains as animal models
*Easily managed
*Quality of immunologic products
*Ease of reproductive control

DISADVANTAGES
*Most colonies are a storehouse of diseases
*Extremely variable to responses to general anesthetics

'''Brief timeline of rabbit embryo model use'''

*1672- de Graaf found the Graffian follicle.
*1890- Walter Heape succeeded first mammalian embryo transfer
*1906- FT Lewis discovered the development of the lymphatic system in rabbit embryos.
*1941- Dr. Pincus succeeded in keeping rabbit embryos developing in the test
*1968- Edwards and Gardner successfully performed the first known embryo biopsy on rabbit embryos

=== Regnier de Graaf (1641–1673) ===
[[image:Ovary_Graaf.jpg|thumb|250px|left|drawing of ovary]]
[[File:Regnier de Graaf.jpg|right]]

'''Discovery of the Graafian Follicles'''

In 1672 de Graaf published ''The Generative Organs of Women'', which was primarily a study of development in the rabbit. When de Graaf discovered large, round welling on the ovaries of rabbits, he assumed they were mammalian eggs. De Graaf also described the corpus luteum.

He summarised the previous works from anatomists, but unable to experience the amazing benefits made by microscopy.
But Antonie van Leeuwenhoek (A microbiologist, 1632 - 1723) argued that the structures now known as Graafian follicles could not be eggs. Haller suggested that the egg might be formed by the coagulation of the fluid within the Graafian follicle. De Graaf noted that the “egg” did not contain a tiny embryo, but he thought it did contain the “germ” of the future organism. (3)

=== Walter Heape (1855-1928) ===
'''First case of embryo transfer experiments'''

On 27 April 1890, Walter Heape (a professor and physician at the University of Cambridge, England) transferred rabbit embryos from one mother to another. (7) One rabbit mother became pregnant and delivered young from the transferred embryos. This was the first mammalian embryo transfer experiment to be successfully completed. His embryo transfer work in perspective as it relates to other contributions of this pioneer in reproductive biology.(7)

In 1891, Walter Heape had been conducting research on reproduction in numerous animal species. Working with two species of rabbits, he flushed embryos from the rabbit fallopian tubes of one breed (Angora) and placed them into the uterus of a recently mated Belgian hare. In the resulting litter, there were 4 Belgians and 2 Angoras. Heape proved that it was possible to take preimplantation embryos and transfer them to a gestational carrier without affecting their development.(7)

===Dr. Gregory Goodwin Pincus (1903-1967) ===

'''Contraceptive pill'''

Dr. Pincus began studying hormonal biology and steroidal hormones early in his career. His first breakthrough came when he was able to produce in vitro fertilization in rabbits (by using chemicals) in 1934. Throughout their hormonal contraceptive research Pincus, along with reproductive physiologist Min Chueh Chang, found out progesterone would act as an inhibitor to ovulation. They co-invented the combined oral contraceptive pill.[2][6]

===Genetic Diagnosis===
In 1968, Robert Edwards and David Gardner reported the successful sexing of rabbit blastocysts, setting the first steps towards PGD (Preimplantation Genetic Diagnosis). It was not until the 1980s that human IVF was fully developed, which coincided with the breakthrough of the highly sensitive polymerase chain reaction (PCR) technology. Handyside and collaborators' first successful attempts at testing were in October 1989 with the first births in 1990 though the preliminary experiments had been published some years earlier. In these first cases, PCR was used for sex determination for patients carrying X-linked diseases.(12)

==Timeline of Embryo Development==

The following is a timeline, adapted from Cibelli (2002), of the main events of preimplantation development in rabbits. The time is measured in hours post-mating and shows the embryo stage (cell number) in each time scale.

[[File:Morula1.JPG|right|200 px|thumb|A day 2 early morula]]

'''12-14 hours:''' Oocyte; Fertilization

'''18-20 hours:''' Zygote; Pronuclear formation

'''24-26 hours:''' Two cell

'''30-32 hours:''' Four cell

'''38-40 hours:''' Eight cell; Maternal-zygotic transition

'''46-48 hours:''' Sixteen cell

'''54-56 hours:''' Morula (32 cell); Compaction and transport to uterus

'''64-66 hours:''' Compact morula (64 cell); Morula-blastocyst transition

'''76-78 hours:''' Early blastocyst (128 cell)

'''84-86 hours:''' Expanded blastocyst (256 cell); Blastocoels expansion

'''94-96 hours:''' Hatched blastocyst (512 cell); Hatching

The following shows a diagrammatic representation of the relative sizes of rabbit embryos. The sizes do not include the embryonic coverings such as the zona pellucida and mucin coat. This diagram has been adapted from Warner (2003).

[[File:Sizes.JPG]]

The following timelines show a comparison of the developmental stages between human and rabbit embryos. They have been adapted from Derelanko (2008). "The similarities of this developmental pattern in humans and rabbits, suggests that the same growth increment is required to achieve the same stage. The main difference observed between human rabbit gestational duration is due to the fetal growth phase. The reason for this may be due to birth weight, lifetime and the neural complexity of the species." (59)

[[File:Timeline_rabbit.JPG]]

The following timelines have been adapted from a study carried out by Beaudoin et al. on the development of rabbit embryos.

==='''Body Form'''===

'''8.5 days''': Embryo thickens. First somites appear. Rostral neuropore closes. Caudal neuropore remains open

'''9.5 days''': Dorsal curvature begins. Cardiac mass bulges under cephalic pole.

'''10.5 - 13.5 days''': Dorsal curvature increases. Body thickens. Softening of the cephalic domination straightens the embryo.

'''17.5 days''': Neck becomes visible.

==='''Limb Development'''===

''' 9.5 days''': Rostral limb bud appears

'''10.5 days''': Caudal limb bud appears

'''12.5 days''': Hand plate becomes present. Limbs become disposed.

'''13.5 days''': Foot plate and finger rays become visible.

'''14.5 days''': Rostral and caudal limbs become parallel.

'''15.5 days''': Elbow appears.

'''16.5 days''': Fingers start to elongate.

'''17.5 days''': Knee becomes visible

'''19.5 days''': Hands and feet merge on the midline. Three segments of limbs become distinguished.

==='''Abdominal Wall Development'''===

'''9.5 days''': Abdominal wall is limited to the embryonic pedicle under the cardiac mass.

'''13.5 days''': First intestinal loops appear in the umbilical cord.

'''14.5 days – 17.5''': Rapid intestinal development in the cord.

'''15.5 days''': Abdominal vesicles can be observed.

'''16.5 days''': Cecal bud becomes present outside the abdomen

'''18.5 days''': Bowel returns to the abdominal cavity and umbilical ring closes.

==='''Cephalic Development'''===

'''9.5 days''': One cerebral vesicle can be seen. Pharyngeal arches as optic vesicle are present.

'''10.5 days''': Three arches are distinguished in the cephalic pole.

'''11.5 days''': Three cerebral vesicles present. Optic plate is distinguished.

'''12.5 days''': Face develops nasal, maxillar and mandibular buds. Lens vesicle is closed. Five cerebral vesicles exist.

'''14.5 days''': The ear becomes refined. Face can be distinguished from the brow.

'''18.5 days''': Eyelid appears, covering the eyes.

==Staging==

The following stages have been adapted from Beaudoin et al. (2003). Table 1 represents at each age its corresponding stage defined by the Carnegie classification

{| class="wikitable" style="text-align:center; width: 800px; height:1000px" border="1"
|+'''Table 1. Rabbit developmental stages using Carnegie classification'''

|- style="height:50px"
! '''Stage''' !! '''Days''' !! '''Event''' !! '''Image'''
|- style="width:200px"
! width="50" | 10
| width="50" | 8.5 || First somites appear, rostral neuropore closes
|- style="height:75px"
! 12
| 9.5 || Rostral limb bud, embryonic pedicle, caudal neuropore closes, one cerebral vesicle, pharyngeal arches, completion of optic vesicle
| [[file: 9.5new.JPG|100px]]
|- style="height:75px"
! 13
| 10.5 || Dosral C-shaped curvature, caudal limb bud, prominent cardiac swelling, four pharyngeal arches
| [[file: 10.5new.JPG|100px]]
|- style="height:75px"
! 14
| 11.5 || Three cerebral vesicles, optic plate, mesonephric ridge
|- style="height:75px"
! 15
| 12.5 || Hand plate, wheel ray limbs, lens vesicle closes, five cerebral vesicles, facial buds, vertebrae
| [[file: 12.5new.JPG|100px]]
|- style="height:75px"
! 16
| 13.5 || Foot plate, finger rays, prominent liver, intestinal loops, auricular hillocks
| [[file: 13.5new.JPG|100px]]
|- style="height:100px"
! 19
| 14.5 || Cuboidal body, trunk straightens, parallel limbs, toe rays, modeled face, visible auricle
| [[file: 14.5new.JPG|100px]]
|- style="height:75px"
! 20
| 15.5 || Elbow, fingers elongate, notches between toe rays
| [[file: 15.5new.JPG|100px]]
|- style="height:75px"
! 21-22
| 16.5 || Toes free, cecal bud in intestinal hernia
| [[file: 16.5new.JPG|100px]]
|- style="height:75px"
! 22-23
| 17.5 || Knee, neck, eyelids
| [[file: 17.5new.JPG|100px]]
|- style="height:75px"
! 23
| 18.5 || Hands and feet join at the midline, closure of abdominal wall, eyelids cover eyes
| [[file: 18.5new.JPG|100px]]
|-
| colspan="4" align="center"| Following this stage fetal appearance is completed, organogenesis is achieved
|}

==Genetics==

===Sequencing===
The National Human Genome Research Institute selected the European rabbit (Oryctolagus cuniculus) for whole genome sequencing to enhance their understanding of the human genome and use it experimentally for an animal model for human disease. (8)

The rabbit has been sequenced twice by The Broad Institute as part of the mammalian genome project. It is now currently undergoing 7 more sequencing projects. Its sequencing is made by the Whole Genome Shotgun (WGS) and assembly method. (9) This is when genomic DNA is sheared into small pieces of approximately 2000 base pairs which are then cloned into plasmids and sequenced on both strands. Once the contig fragments are read, realigned and reassembled by computer algorithms, it will give the overall sequence. (10) (11) The image below shows diagramatically how the two types of sequencing are different. The same techniques are used for sequencing the human genome (in 2003). [A contig is a set of overlapping DNA segments, derived from a single source of genetic material, from which the complete sequence may be deduced.

The whole genome shotgun (WGS) has serious gaps, yet the information has already proven useful for immunological as well as in silico studies. Deeper 7x coverage started in September 2007. The NCBI Rabbit Genome Resources site has links to searches for genes in the assemblies of the 2x WGS sequence at Ensembl and UCSC.(12) [http://www.broadinstitute.org/models/europeanrabbit/ Rabbit Genome Project]

[[File:WGS_sequencing.gif‎|center|800 px]]

===Genome===
The Rabbit genome was published by two groups (9)
# Lindblad-Toh,K., Chang,J.L., Gnerre,S., Clamp,M. and Lander,E.S. published their admission of 84024 bases on May 5th 2005 to The Broad Institute (USA) by shotgun sequencing
# Di Palma,F., Heiman,D., Young,S., Gnerre,S., Johnson,J., Lander,E.S. and Lindblad-Toh,K. published their admission of 84024 bases on August 3rd 2009 to The Broad Institute (USA) by shotgun sequencing.
The rabbit's genome is sequenced and on display in the Nucleotide Data Bank. It is too long to produce here. A link to the data bank is provided: [http://www.ncbi.nlm.nih.gov/nuccore/256946799/ Rabbit Genome from the Nucleotide Data Bank]

[[File:8cellembryo.jpg|thumb|Individual mitochondria (arrowheads) of an 8cell Rabbit embryo]]

The rabbit genome was sequenced in 2005 by Ensembl and managed to produce: (13)
* 2,076,044,328 supercontigs (ordered Contigs with gaps)
* 495 Known protein-coding genes
* 11,357 Projected protein-coding genes
* 2,343 RNA genes
* 212,581 Gene exons
* 20,311 Gene transcripts

For further research the taxonomy ID number for the Rabbit is: 9986 [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=9986&lvl=3&lin=f&keep=1&srchmode=1&unlock/ Taxonomy Data]

===Mitochondrial Genome===
The mitochondiral genome (mtDNA) of the rabbit was sequenced on November 14th 2006 with 17245 base pairs/nucleotides in circular form. Apparently the "length is not absolute due to the presence of different numbers of repeated motifs in the control region".
PMID 9653643

The image to the right shows the mitochondria during cell division and multiplication in embryo development.

=== Chromosomes ===
Over the years there have been various data suggesting the diploid chromosomal number for the rabbit may range from 22-42. However through recent research and an abundance of trials suggest that the rabbit does indeed have 22 different chromosome pairs existing in each cell of the rabbit. (16)(17) The sex chromosomes of the rabbit are of X-Y type convincingly (17). In a study in Bombay it confirmed that a rabbit has 2n = 44 chromosomes. There were 21 pairs of autosomes, out of which 1 to 6 were metacentric, 7 to 11 submetacentric, 12 to 17 subtelocentric and 18 to 21 acrocentric, plus the sex chromosomes. The image to the left shows a female rabbit with no chromosomal abnormalities. (19)

'''Comparison to human chromosome:'''

Rabbit chromosomes 12, 19 and X were found to be completely homologous to human chromosomes 6, 17 and X, respectively. All other human chromosomes were homologous to two or sometimes three rabbit chromosomes. (14) Chromosome 12 was shorter than chromosomes 13 and 14. (15) The image below illustrates the human chromosome (2n = 46).

[[File:Drawn chromosome.jpg|left|400 px]]

[[File:Karyotypehuman.gif|right|500 px]]

'''Abnormalities'''

These are generally more apparent during early embryo development in blastocysts from delayed fertilization. Some examples of abnormal development include cases of: (18)
* hypoploidy; 1 chromosome missing from a pair (2n = 43),
* double hypoploidy; 2 chromosomes missing from 2 different pairs (2n = 42),
* mosaicism (different chromosomal makeup in some cells).

Another study also found these abnormalities as well as: (19)
* autosomal trisomy (3 autosomes per pair),
* triploidy (extra set of chromsomes),
* mixoploidy (unequal number of chromosome sets in adjacent cells), and
* short arm deletion (deletion of parts of chromosomes).

A specific abnormality occurring in rabbits is the x-linked tremor. There is a mutation in exon 2 of the prteolipid-protein (PLP 1) gene, corresponding to the end of the first potential transmembrane domain of the protein. This disorder affects myelination of the central nervous system. OMIA ID:12 [http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=full_report&list_uids=100009169&log$=omiamaingene| Gene:100009169]

==Abnormal Development==

Abnormal embryological development is a vast field of study that has been the subject of recent research papers. Our investigation of abnormal development in rabbit embryology will focus on abnormalities commonly found in both rabbit and human embryos. We will explore the nature of these abnormalities in both humans and rabbits.

[[File:Normal v Abnormal.jpg|right|300 px|thumb|Brain MRI of patient with Hydrocephalus (left) compared to a normal brain (right). An obvious increase in ventricular size and a significant decrease in brain size is present.]]
[[File:Ventricle_Expansion.jpg|right|300 px|thumb|CSF accumulation in ventricles of brain increasing intracranial pressure.The pressure from the expanding ventricles force the brain and skull to grow outwards abnormally.]]

'''Hydrocephalus'''

Annually, one in every 1000 children born in Australia have hydrocephalus. Hydrocephalus occurs when excessive cerebrospinal fluid (CSF) accumulates in the brain and can result in severe disability and even death because the disorder can result in complete or near complete destruction of the cerebral cortex (22).

Children born with hydrocephalus typically exhibit abnormally large head circumference and bulging cranial fontanels as a result of increased intracranial pressure on the brain from the accumulating CSF (22,23). As CSF accumulates in the ventricles and CSF compartments of the brain, it expands forcing the brain to grow outward. The outward growing brain places pressure on the skull which in turn also grows outwards giving rise to an abnormally large head circumference and bulging cranial fontanels (22,24). It is generally acknowledged that children with hydrocephalus have mental retardation, often to the degree of being “vegetative” (24).

The serious consequences of this disease mean that much research is necessary to unearth methods of prevention and effective treatment. One of the modes of studying hydrocephalus is to use the rabbit experimental model where hydrocephalus can be induced in rabbit embryo’s. The injection of silicone oil into the cisterna magna of the brain is one way of inducing hydrocephalus in the rabbit embryo. The silicone oil obstructs the normal flow of CSF resulting in CSF accumulation in the brain leading to hydrocephalus (25). Another method of inducing hydrocephalus in rabbit embryo’s is by intentional vitamin A deprivation of pregnant dams. The vitamin A deficiency results in raised intracranial CSF pressure and aqueduct stenosis causing poor circulation of CSF leading to hydrocephalus (26,27). Although the exact function of vitamin A on brain development and CSF regulation is not fully understood, it is clear that Vitamin A has an important role in brain development and its normal functioning (27).
[[File:Rabbithhdrocephalus.jpg|center|300 px|thumb|Young rabbit with hydrocephalus caused by Vitamin A deficiency. Note the abnormally shaped cranium inflamed in appearance.]]

[[File:SpinabifidaMeningocele1.jpg|right|300 px|thumb|Spina Bifida Meningocele has characteristic damage to the meninges of the spinal cord which are pushed out through an opening in the vertebrae as a cyst filled with CSF.]]
[[File:SpinaBifidaMyelomeningocele.jpg|right|300 px|thumb|Spina Bifida Myelomeningocele is the most severe form of spinabifida where the damaged spinal cord protrudes out with damaged meninges as a cyst filled with CSF.]]
[[File:SpinaBifidaOcculta1.jpg|right|300 px|thumb|Spina Bifida Occulta is the least severe as the spinal cord and meninges are undamaged.]]

'''Spina Bifida'''

In Australia, the risk of spina bifida is 1 in every 500 pregnancies. Spina bifida is a type of neural tube defect where vertebrae (which normally cover and protect the spinal cord) are not completely formed but are divided resulting in the defective spinal cord and its coverings to protrude through the opening (28,29).

There are three main types of Spina Bifida differentiated by their characteristic features:

1)Spina Bifida Meningocele characterized by normal spinal cord, divided outer vertebrae and meninges surrounding the spinal cord protruding from the divided vertebrae as a cyst (1,28).

2)Spina Bifida Myelomeningocele characterized by split outer vertebrae with spinal cord and its meninges protruding from the divided vertebrae as a cyst. Commonly found at lumbar vertebral level (1,28,29).

3)Spina Bifida Occulta characterized unfused vertebral arches and exposed vertebral canal. Spinal cord and its meninges still located in vertebral canal (1,28).

All forms of spina bifida are potentially fatal and in those where the spinal cord is damaged severe consequence arise including and paralysis and loss of sensation at and below the level of damage spinal cord damage (29,33). There is a lot of Spina bifida research using rabbit models to test the effective methods of correcting spina bifida. The occurrence of natural spina bifida in rabbits is rare and for experimental purposes it can be surgically created in rabbit fetuses during gestation (31,32). The process involves aesthetical sedation of the maternal rabbit at day 22 of gestation; a midline laparotomy performed and the desired type of spina bifida lesion created on the exposed fetus using forceps. Different methods for correcting spina bifida can then be tested and its effectiveness analysed (30,33,34).
[[File:Rabbitspinabifida1.jpg|center|350 px|thumb|Rabbit newborn with Spina Bifida. Note the unfused, divided vertebrae and exposed spinal cord.]]

'''Brachydactylia & Acheiropodia'''

[[File:Malformation1.jpg|right|150 px|thumb|Acheiropodia in rabbit characterized by amputations of the limbs and extremities.]]

[[File:Rabbitmalformation3.jpg|left|150 px|thumb|X-Ray study of rabbit limbs with malformed phalanges due to Brachydactylia.]]

Brachydactylia and Acheiropodia are genetic disorders characterized by skeletal malformation of the hands and feet (36,36). In Brachydactylia, the malformations commonly involve abnormal shortening of fingers and toes due to poorly formed or absent bones (35). Acheiropodia is characterized by more severe skeletal malformations including bilateral amputations of the distal upper and lower extremities as well as aplasia of the hands and feet. Although it is not fatal, the individual endures a very difficult life without hands and feet (37).

The inheritance mechanism of this diseases can has been studied through experiment using rabbits. Rabbits with abnormal genes coding for Brachydactylia and Acheiropodia are selected and bred to produce offspring with the disease (36). Brachydactylia and Acheiropodia are autosomal recessive disorders which means that two copies of an abnormal gene must be present in the affected individual in order for the disease to develop. Thus, each parent passes an abnormal gene to the offspring (35,36). The process of the malformation progresses from genotype to phenotype; small deletions on the chromosomes produce abnormal genes, the abnormal genes are then passed down to the offspring, the offspring that inherits two of the abnormal genes is unable to code for the correct proteins and as a result, there is failure in normal development of limb extremities in the embryo phenotype (37,38).

==Current Embryology Research==

There is currently great excitement in research involving rabbits in the fields of transgenesis, cloning and stem cells. We shall explore research in these areas by discovering some of the techniques used and how they have been applied to the rabbit model.

[[File:Trans1.jpg|right|170 px]]
[[File:Trans2.jpg|right|170 px]]
[[File:Trans3.jpg|right|170 px]]
[[File:Trans4.jpg|right|170 px]]
[[File:Trans5.jpg|right|170 px]]

'''Transgenic rabbit'''

A transgenic organism is one whose genome also contains genes from another species (39). The aim of creating a transgenic organism is to obtain a favorable characteristic in the organism’s phenotype (41). This desired characteristic of phenotype is obtained by altering the organism’s normal genotype to include the gene from another species with the desired characteristic (39,40).

The production of a transgenic organism involves several steps summarized below:

1) The chromosome and the desired gene on it are identified in an organism (39).

2) The gene is isolated from its DNA strand. This involves “cutting” it out of its DNA strand using enzymes called restriction endonucleases. The restriction endonucleases cut DNA at specific site so the desired gene can be removed from the DNA strand. The cut ends are known as “sticky ends” (39,40).

3) Separate DNA sequences for regulation sometimes have to be added to ensure the gene will work (40).

4) The gene is then inserted with a promoter sequence into the fertilized egg cell of a new organism producing recombinant DNA (39,44). To do this, firstly the new organism’s cell DNA must first be cut and the desired gene incorporated into it. The same enzymes are used to cut the new organism’s cell DNA because the DNA stands from the two different organisms will form matching sticky ends that will be attracted to and connect with each other in a process is called “annealing” (39,40,44).

5) DNA ligases are sealing enzymes found in all living organisms that help make and repair DNA (39,40). The DNA ligases are added to the annealed DNA fragments to help strengthen the bonds of the new recombinant DNA. The recombinant DNA is now transferred into the new organism’s fertilized egg by microinjection (44).

6) As the embryo develops and the recombinant genetic code read, new proteins are synthesized which code for the new desired phenotype characteristic in the transgenic organism (39,40).

Transgenic rabbits can be created in the laboratory by gene microinjection into the fertilized rabbit oocyte (44). In April 2000, a transgenic rabbit named Alba was born containing a gene from a Pacific Northwest jellyfish. The gene which was injected into a fertilized albino rabbit oocyte allows the rabbit to synthesize the green fluorescent protein (GFP) that is characteristic of the Pacific Northwest jellyfish. When illuminated correctly, Alba glows a bright green (43,46).

Transgenic rabbits have important research purposes. Transgenic rabbits can be created to model retinal degeneration (44). Retinal degeneration is a common problem with aging and diseases such as diabetes, and frequently leads to complete blindness (42). A genetic retinal degeneration disease called retinitis pigmentosa (RP) is created in these rabbits by introducing the “Pro347Leu” mutation of the rhodopsin gene into fertilized rabbit eggs (43,44). As the rabbit grows, it develops the disease which becomes progressively worse (45).
The use of these transgenic rabbits ultimately leads to better understanding of the disease and more effective treatments (42). [[File:Transgenic rabbit.jpg|center|250 px|thumb|"Alba" A trangenic rabbit with a gene from a Pacific Northwest jellyfish that allows it to synthesize the green fluorescent protein (GFP) of the jellyfish.]]

[[File:Crabbit 1.jpg|right|170 px]]
[[File:Rabbit2.jpg|right|170 px]]
[[File:Rabbit3.jpg|right|170 px]]
[[File:Crabbit 4.jpg|right|170 px]]

'''Cloning'''

Cloning is a method of producing genetically identical organisms. The principle of cloning relies on “tricking” an egg cell to begin rapidly dividing into an embryo (39). In the normal fertilization process, two haploid sex cells unite to form a diploid zygote which begins rapidly dividing into an embryo (40). By replacing the haploid egg cell nucleus with a diploid somatic cell nucleus, the egg cell is tricked into thinking it is fertilized and hence begins rapidly dividing to form an embryo (39,40,41).

The process of cloning involves several steps summarized as the following using a rabbit example:

1) A somatic cell is obtained from a rabbit and the nucleus removed (39).

2) An egg cell is obtained from a donor rabbit and the nucleus of the egg cell removed using an enucleation needle. The cell is now called an enucleated egg cell (egg cell without a nucleus) (39,41).

3) The nucleus of the somatic cell is inserted into the enucleated egg cell (41).

4) The cell is now stimulated to divide by applying pulses of electric current (39).

5) The rapidly dividing cell develops in culture for a few days forming the early embryo (40,41).

6) The embryo is then implanted into the uterus of another rabbit similar to the egg cell donor. This rabbit is called the surrogate mother (40,41).

7) The embryo develops and the surrogate mother gives birth to a rabbit fetus with near identical genotype of the somatic cell donor (the small genomic difference is caused by the fetus obtaining mitochondrial DNA from the egg cell donor) (39,41).

The cloning of rabbits has been achieved by inserting the diploid nucleus of a rabbit fibroblast (the principal cells in connective tissue) into an enucleated oocyte (49). There is currently much focus on the creation of controversial but revolutionary interspecies hybrid embryos where the nucleus from a human somatic cells are implanted into an enucleated egg cell of another animal (50). The resulting embryo (known as a chimera) will be almost completely human genotype but will have genome from the other animal (48). In 2003, scientists at the Shanghai Second Medical University fused human cell with rabbit eggs creating the first human-rabbit hybrid using the nucleus transfer technique. The hybrid embryo developed in culture for a few days before it was destroyed and the stem cells harvested (47,48). The purpose of the research into creating hybrid embryos is to provide researchers with human stem cells for experimentation into cures for diseases such as cystic fibrosis, Alzheimer’s and Motor Neuron disease as human stem cell are difficult to obtain (50).

[[File:Rabbit clone.jpg|center|450 px|thumb|(A) Cloned rabbits (5 month old) from nuclear transfer technique. (B) The male rabbit whose fibroblasts were used as the nuclear donors. The cloned rabbits have almost identical genome to the male donor.]]

'''Stem Cells'''
[[File:HES.jpg|right|200 px|thumb|Human Embryonic Stem cell (hES).]]
[[File:Rabbit knee.jpg|right|200 px|thumb|Stem cell induced cartilage repair of knee in rabbit.]]

Stem cells are unspecialized cells which are able to continuously reproduce themselves and under appropriate conditions, differentiate into all the various specialized cells of the organism such as cardiac cells, neurons and blood cells (39,40). Adults have a small number of stem cells when compared to a developing embryo and the stem cell of an embryo more easily obtained (41). Human embryonic stem cells (hES) derived from the inner mass of the preimplantation blastocyst have the potential to differentiate into all cell types in the human body and thus are valued by researchers (50). However, due to ethical and political issues, the obtaining and experimentation on human embryonic stem cells is difficult and alternate means are needed as stem cell provides potentially new treatments for a range of diseases (54).

Rabbits can be used both in the obtaining of stem cell for experimentation and also as recipients of stem cells to cure diseases. The human-rabbit hybrid embryo provides a method of obtaining stem cells for experimentation and these stem cells possess many similar properties to human stem cells, including expression of surface markers, special growth requirements, capabilities of self renewal, formation of embryonic body and differentiation into cells of all three germ layers (53).

Stem cell experimentation on rabbits also focuses on transplanting stem cell into rabbits to treat specific diseases. A study at Zhejiang University where a research team transplanted human mesenchymal stem cell into New Zealand white rabbits with myocardial infarction recoded regeneration of vascular structure and improvement in cardiac function. The research team noted the potential of stem cells in differentiating into specialized cardiac cells when subjected to the specific conditions of the rabbit heart (52).

Another study at Hallym University tested the effectiveness of transplanting mesenchymal stem cells from New Zealand white rabbits into damaged cartilage in the knees of other New Zealand white rabbits. In the experiment, mesenchymal stem cells were obtained from the rabbit bone marrow and injected into the knees of other rabbits that had cartilage in their knees surgically damaged. The research team were able to conclude notable cartilage recovery in the rabbits with the mesenchymal stem cell injection and the potential of mesenchymal stem cells to differentiate into fibroblasts, adipoblasts, osteoblasts and chondroblasts (51,53).

The findings in stem cell experimentation with in rabbits yielded positive results and potentially opens a new field of research in the use of stem cell to treat a range of diseases in humans.

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# Patten, B.M (1953). Embryological stages in the establishing of myeloschisis with spina bifida. The American journal of anatomy, 93(3), Retrieved from [http://deepblue.lib.umich.edu/handle/2027.42/49611]
# Pedreira, D.A, & Valente P.R (2003). Successful Fetal Surgery for the Repair of a 'Myelomeningocele-Like' Defect Created in the Fetal Rabbit. Fetal Diagnosis and Therapy, 18. Retrieved from [http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowPDF&ProduktNr=224239&Ausgabe=229041&ArtikelNr=69378]
# Lecklitner, M.L, & Douglas K.P (1986). Osteoscintigraphy and brachydactylia of the hand . European Journal of Nuclear Medicine and Molecular Imaging, 12(9), Retrieved from [http://www.springerlink.com/content/t82l77282x579102/]
# Greene, H.S, & Saxton J.A (1938). HEREDITARY BRACHYDACTYLIA AND ALLIED. ABNORMALITIES IN THE RABBIT. THE JOURNAL OF EXPERIMENTAL MEDICINE , 69. Retrieved from [http://jem.rupress.org/cgi/reprint/69/2/301.pdf]
# P. Ianakiev, M. van Baren, M. Daly, S. Toledo, M. Cavalcanti, J. Neto, E. Silveira, A. Freire-Maia, P. Heutink, M. Kilpatrick. Acheiropodia Is Caused by a Genomic Deletion in C7orf2, the Human Orthologue of the Lmbr1 Gene. The American Journal of Human Genetics, 68. Retrieved from [http://linkinghub.elsevier.com/retrieve/pii/S0002929707624707]
# Walbaum, R, Hazard, C, & Cordier, R (1976). Brachydactylia with symphalangism, probably autosomal recessive . Human Genetics, 33(2), Retrieved from [http://www.springerlink.com/content/m630p6880661486n]
# Campbell, N.A, & Reece, J.B (2002). Biology 6th Edition. USA: Benjamin Cummings.
# Solomon, E.P, Berg, L.R, & Martin, D.W (2002). Biology 6th Edition. USA: Thompson Learning.
# Glanville, A.R (2008). Scientifica. NSW, Australia: Millennium House.
# Lund, R.D (2008). Saving Vision with Skin Cells. Retrieved from [http://www.blindness.org]
# Jones, B.W, & Marc R.E (2008). Computational Molecular Phenotyping and Excitation Mapping in the P347L. Retinal Degeneration , (2986), Retrieved from [http://prometheus.med.utah.edu/]
# Kondo, M, Sakai, T, & Ueno, S (2009). Generation of a Transgenic Rabbit Model of Retinal Degeneration. Investigative Ophthalmology and Visual Science, 50. Retrieved from [http://www.iovs.org/cgi]
# Punzo, C, Chen, B, & Roesch, K (2009). PHOTORECEPTOR DEATH IN MOUSE MODELS OF RETINITIS PIGMENTOSA. Retrieved from [http://genepath.med.harvard.edu]
# Zimmer, M (2008). Alba. Retrieved from [http://www.conncoll.edu/ccacad/zimmer/GFP-ww/cooluses8.html]
# Scott, C (2006, May 1). Chimeras in the crosshairs. Nature Biotechnology , 24, Retrieved from [http://www.nature.com/nbt/journal/v24/n5/abs/nbt0506-487.html]
# Mott, M (2005, January 25). Animal-Human Hybrids Spark Controversy. National Geographic News, Retrieved from [http://theyfly.com/PDF/Nat.%20Geo.%20Animal-Human%20Hybrids.pdf]
# Li, S, & Chen X (2006). Rabbits generated from fibroblasts through nuclear transfer . Society for Reproduction and Fertility, 131. Retrieved from [http://www.reproduction-online.org/cgi/reprint/131/6/1085]
# Minger, S (2007). Interspecies SCNT derived human embryos. Regenerative Medicine, 2(2), Retrieved from [http://www.futuremedicine.com]
# Koga, H, Shimaya, M, & Muneta, T (2008). Local adherent technique for transplanting mesenchymal stem cells as a potential treatment of cartilage defect. Arthritis Research & Therapy, 10(4), Retrieved from [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2575632]
# Wang, J, Li, C, & Sun, Y (2005). Human bone marrow-derived mesenchymal stem cells transplanted into damaged rabbit heart to improve heart function. Journal of Zhejiang University Science, 6(4), Retrieved from [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1389731]
# Chen, Y, Liu, A, & Mao, W (2003). Embryonic stem cells generated by nuclear transfer of human somatic nuclei into rabbit oocytes. Cell Research , 13(4), Retrieved from [http://www.nature.com]
# Bethesda (2009, September 23). Stem Cell Information. Retrieved from [http://stemcells.nih.gov]
# Cibelli, J. B. (2002). Principles of cloning Amsterdam. Academic Press
# European rabbit (oryctolagus cuniculus) Retrieved 9/21/2009, 2009, from http://www.feral.org.au/content/species/rabbit.cfm
# Warner, S. (2003). Inositol transport in preimplantation rabbit embryos: Effects of embryo stage, sodium, osmolality and metabolic inhibitors Reproduction, 125(4), 479-493.
# Derelanko, M. J. (2008). The toxicologist's pocket handbook, second edition Informa HealthCare
# Beaudoin, S., Barbet, P., & Bargy, F. (2003). Developmental stages in the rabbit embryo: Guidelines to choose an appropriate experimental model Fetal Diagnosis and Therapy, 18(6), 422-427.

==Glossary==

Anesthetic - A drug that causes temporary loss of bodily sensations

Aplasia - The absence or defective development of a tissue or organ

Blastocyst - A stage of embryo development that occurs about five days after fertilisation when the embryo contains quite a few cells

Caudal - Situated towards the inferior or posterior end of the body

Cephalic - Relating to the head

Cerebral Aqueduct - A canal filled with cerebrospinal fluid within the midbrain

Cerebral Cortex - The layer of unmyelinated neurons (the grey matter) forming the cortex of the cerebrum of the brain

Cerebro Spinal Fluid (CSF) - A watery fluid which flows in the cavities within the brain and around the surface of the brain and spinal cord

Chromosome - Microscopic carriers of genetic material, composed of deoxyribonucleic acid (DNA) and proteins and appearing as rods under a microscope

Cisterna Magna - is one of three principal openings in the subarachnoid space between the arachnoid and pia mater layers of the meninges surrounding the brain

Diploid - A full set of genetic material, consisting of paired chromosomes one chromosome from each parental set

Dorsal - Position towards the back

Fontanel - Membranous gap between the bones of the cranium in an infant or fetus

Genome - All genetic information, the entire genetic complement and all of the hereditary material possessed by an organism. Made up of both chromosomal genome (inside the nucleus of the cell in the familiar form of chromosomes) and mitochondrial genome (outside the nucleus in the cytoplasm of the cell, usually in the form of one round chromosome (the mitochondrial chromosome))

Genotype - The genetic makeup of an organism

Glucocorticoids - A class of steroid hormones that bind to the glucocorticoid receptor (GR), which is present in almost every vertebrate

Haploid - A single set of chromosomes (half the full set of genetic material)

Laparotomy- Surgical incision into the abdominal wall; often done to examine abdominal organs

Ligases - Group of enzymes that catalyze the binding of two molecules

Oocyte - A female gametocyte that develops into an ovum after two meiotic divisions

Phenotype - The observable traits or characteristics of an organism, for example hair color, weight, or the presence or absence of a disease.

Pronuclear - Haploid nucleus before fusion of nuclei in fertilisation

Restriction Endonucleases - Enzymes that recognize and cleave specific DNA sequences, generating either blunt or single-stranded (sticky) ends

Retina - The thin layer of cells at the back of the eyeball where light is converted into neural signals sent to the brain

Rostral - Situated toward the oral and nasal region

Somite - Blocks of mesoderm on either side of the notochord and neural tube during development of the vertebrate embryo. Develop into muscles and vertebrae

Stenosis - Abnormal narrowing of a bodily canal or passageway

Weaning - Young become accustom to nourishment other than suckling

==Links to Research Laboratories and Researchers==

1) Transgenic lab: [http://www.dnavision.be/index.php]

Involved in development of transgenic organisms, DNA construction and phenotype analysis.

2) World Rabbit Science Association: (WRSA) [http://world-rabbit-science.com]

International Association where researchers exchange knowledge and encourage teaching, scientific research, practical experimentation, the collection and publication of statistics and documents relating to the rabbit. Even have their own journal called “World Rabbit Science”

Website provides contact with researchers, professors and veterinarians working with rabbits.

Example: Dr. Myriam Kaplan-Pasternak, Doctorate Veterinary Medicine, University of California, myriamsemail@gmail.com

3) American Veterinary Medical Association [http://www.avma.org]

The American Veterinary Medical Association (AVMA), established in 1863, is a not-for-profit association representing more than 78,000 veterinarians working in private and corporate practice, government, industry, academia, and uniformed services. Excellent website into animal research and has a range of veterinary journals.

{{Template:Projects09}}
[[Category:Rabbit]]
[[File:Example.jpg]]

2009 Group Project 1

2009-10-14T12:21:24Z

Z3185685: /* Current Embryology Research */

[[File:Rabbits.png|right|400 px]]

== '''THE RABBIT (ORYCTOLAGUS CUNICULUS)''' ==

==Introduction==

[[File:Isidro_Martinez.jpg‎|left|175 px]]

Several characteristics of the rabbit make it an excellent model for study. This will be further explored in "The History of Model Use" section of this page. Many studies have resulted in the development and improvement of various micro-manipulation techniques such as the production of transgenic rabbits. Unlike many other species such as the chick or rat, relatively little is known about the development of a rabbit. Nevertheless, it is still an appropriate animal model as the results from many experiments are significant to that of other mammals, including humans. (55)

A rabbits potential for reproduction is high, breeding from the early stages of 3 to 4 months of age. A mature female rabbit can be pregnant from 6 to 8 months in a year, producing up to 30 to 40 young in this time. (56)

==History of Model Use==

'''WHY are we using rabbits?'''

ADVANTAGES
*Provides repeatability of animal model studies
*Large enough for single samples
*Many stocks/strains as animal models
*Easily managed
*Quality of immunologic products
*Ease of reproductive control

DISADVANTAGES
*Most colonies are a storehouse of diseases
*Extremely variable to responses to general anesthetics

'''Brief timeline of rabbit embryo model use'''

*1672- de Graaf found the Graffian follicle.
*1890- Walter Heape succeeded first mammalian embryo transfer
*1906- FT Lewis discovered the development of the lymphatic system in rabbit embryos.
*1941- Dr. Pincus succeeded in keeping rabbit embryos developing in the test
*1968- Edwards and Gardner successfully performed the first known embryo biopsy on rabbit embryos

=== Regnier de Graaf (1641–1673) ===
[[image:Ovary_Graaf.jpg|thumb|250px|left|drawing of ovary]]
[[File:Regnier de Graaf.jpg|right]]

'''Discovery of the Graafian Follicles'''

In 1672 de Graaf published ''The Generative Organs of Women'', which was primarily a study of development in the rabbit. When de Graaf discovered large, round welling on the ovaries of rabbits, he assumed they were mammalian eggs. De Graaf also described the corpus luteum.

He summarised the previous works from anatomists, but unable to experience the amazing benefits made by microscopy.
But Antonie van Leeuwenhoek (A microbiologist, 1632 - 1723) argued that the structures now known as Graafian follicles could not be eggs. Haller suggested that the egg might be formed by the coagulation of the fluid within the Graafian follicle. De Graaf noted that the “egg” did not contain a tiny embryo, but he thought it did contain the “germ” of the future organism. (3)

=== Walter Heape (1855-1928) ===
'''First case of embryo transfer experiments'''

On 27 April 1890, Walter Heape (a professor and physician at the University of Cambridge, England) transferred rabbit embryos from one mother to another. (7) One rabbit mother became pregnant and delivered young from the transferred embryos. This was the first mammalian embryo transfer experiment to be successfully completed. His embryo transfer work in perspective as it relates to other contributions of this pioneer in reproductive biology.(7)

In 1891, Walter Heape had been conducting research on reproduction in numerous animal species. Working with two species of rabbits, he flushed embryos from the rabbit fallopian tubes of one breed (Angora) and placed them into the uterus of a recently mated Belgian hare. In the resulting litter, there were 4 Belgians and 2 Angoras. Heape proved that it was possible to take preimplantation embryos and transfer them to a gestational carrier without affecting their development.(7)

===Dr. Gregory Goodwin Pincus (1903-1967) ===

'''Contraceptive pill'''

Dr. Pincus began studying hormonal biology and steroidal hormones early in his career. His first breakthrough came when he was able to produce in vitro fertilization in rabbits (by using chemicals) in 1934. Throughout their hormonal contraceptive research Pincus, along with reproductive physiologist Min Chueh Chang, found out progesterone would act as an inhibitor to ovulation. They co-invented the combined oral contraceptive pill.[2][6]

===Genetic Diagnosis===
In 1968, Robert Edwards and David Gardner reported the successful sexing of rabbit blastocysts, setting the first steps towards PGD (Preimplantation Genetic Diagnosis). It was not until the 1980s that human IVF was fully developed, which coincided with the breakthrough of the highly sensitive polymerase chain reaction (PCR) technology. Handyside and collaborators' first successful attempts at testing were in October 1989 with the first births in 1990 though the preliminary experiments had been published some years earlier. In these first cases, PCR was used for sex determination for patients carrying X-linked diseases.(12)

==Timeline of Embryo Development==

The following is a timeline, adapted from Cibelli (2002), of the main events of preimplantation development in rabbits. The time is measured in hours post-mating and shows the embryo stage (cell number) in each time scale.

[[File:Morula1.JPG|right|200 px|thumb|A day 2 early morula]]

'''12-14 hours:''' Oocyte; Fertilization

'''18-20 hours:''' Zygote; Pronuclear formation

'''24-26 hours:''' Two cell

'''30-32 hours:''' Four cell

'''38-40 hours:''' Eight cell; Maternal-zygotic transition

'''46-48 hours:''' Sixteen cell

'''54-56 hours:''' Morula (32 cell); Compaction and transport to uterus

'''64-66 hours:''' Compact morula (64 cell); Morula-blastocyst transition

'''76-78 hours:''' Early blastocyst (128 cell)

'''84-86 hours:''' Expanded blastocyst (256 cell); Blastocoels expansion

'''94-96 hours:''' Hatched blastocyst (512 cell); Hatching

The following shows a diagrammatic representation of the relative sizes of rabbit embryos. The sizes do not include the embryonic coverings such as the zona pellucida and mucin coat. This diagram has been adapted from Warner (2003).

[[File:Sizes.JPG]]

The following timelines show a comparison of the developmental stages between human and rabbit embryos. They have been adapted from Derelanko (2008). "The similarities of this developmental pattern in humans and rabbits, suggests that the same growth increment is required to achieve the same stage. The main difference observed between human rabbit gestational duration is due to the fetal growth phase. The reason for this may be due to birth weight, lifetime and the neural complexity of the species." (59)

[[File:Timeline_rabbit.JPG]]

The following timelines have been adapted from a study carried out by Beaudoin et al. on the development of rabbit embryos.

==='''Body Form'''===

'''8.5 days''': Embryo thickens. First somites appear. Rostral neuropore closes. Caudal neuropore remains open

'''9.5 days''': Dorsal curvature begins. Cardiac mass bulges under cephalic pole.

'''10.5 - 13.5 days''': Dorsal curvature increases. Body thickens. Softening of the cephalic domination straightens the embryo.

'''17.5 days''': Neck becomes visible.

==='''Limb Development'''===

''' 9.5 days''': Rostral limb bud appears

'''10.5 days''': Caudal limb bud appears

'''12.5 days''': Hand plate becomes present. Limbs become disposed.

'''13.5 days''': Foot plate and finger rays become visible.

'''14.5 days''': Rostral and caudal limbs become parallel.

'''15.5 days''': Elbow appears.

'''16.5 days''': Fingers start to elongate.

'''17.5 days''': Knee becomes visible

'''19.5 days''': Hands and feet merge on the midline. Three segments of limbs become distinguished.

==='''Abdominal Wall Development'''===

'''9.5 days''': Abdominal wall is limited to the embryonic pedicle under the cardiac mass.

'''13.5 days''': First intestinal loops appear in the umbilical cord.

'''14.5 days – 17.5''': Rapid intestinal development in the cord.

'''15.5 days''': Abdominal vesicles can be observed.

'''16.5 days''': Cecal bud becomes present outside the abdomen

'''18.5 days''': Bowel returns to the abdominal cavity and umbilical ring closes.

==='''Cephalic Development'''===

'''9.5 days''': One cerebral vesicle can be seen. Pharyngeal arches as optic vesicle are present.

'''10.5 days''': Three arches are distinguished in the cephalic pole.

'''11.5 days''': Three cerebral vesicles present. Optic plate is distinguished.

'''12.5 days''': Face develops nasal, maxillar and mandibular buds. Lens vesicle is closed. Five cerebral vesicles exist.

'''14.5 days''': The ear becomes refined. Face can be distinguished from the brow.

'''18.5 days''': Eyelid appears, covering the eyes.

==Staging==

The following stages have been adapted from Beaudoin et al. (2003). Table 1 represents at each age its corresponding stage defined by the Carnegie classification

{| class="wikitable" style="text-align:center; width: 800px; height:1000px" border="1"
|+'''Table 1. Rabbit developmental stages using Carnegie classification'''

|- style="height:50px"
! '''Stage''' !! '''Days''' !! '''Event''' !! '''Image'''
|- style="width:200px"
! width="50" | 10
| width="50" | 8.5 || First somites appear, rostral neuropore closes
|- style="height:75px"
! 12
| 9.5 || Rostral limb bud, embryonic pedicle, caudal neuropore closes, one cerebral vesicle, pharyngeal arches, completion of optic vesicle
| [[file: 9.5new.JPG|100px]]
|- style="height:75px"
! 13
| 10.5 || Dosral C-shaped curvature, caudal limb bud, prominent cardiac swelling, four pharyngeal arches
| [[file: 10.5new.JPG|100px]]
|- style="height:75px"
! 14
| 11.5 || Three cerebral vesicles, optic plate, mesonephric ridge
|- style="height:75px"
! 15
| 12.5 || Hand plate, wheel ray limbs, lens vesicle closes, five cerebral vesicles, facial buds, vertebrae
| [[file: 12.5new.JPG|100px]]
|- style="height:75px"
! 16
| 13.5 || Foot plate, finger rays, prominent liver, intestinal loops, auricular hillocks
| [[file: 13.5new.JPG|100px]]
|- style="height:100px"
! 19
| 14.5 || Cuboidal body, trunk straightens, parallel limbs, toe rays, modeled face, visible auricle
| [[file: 14.5new.JPG|100px]]
|- style="height:75px"
! 20
| 15.5 || Elbow, fingers elongate, notches between toe rays
| [[file: 15.5new.JPG|100px]]
|- style="height:75px"
! 21-22
| 16.5 || Toes free, cecal bud in intestinal hernia
| [[file: 16.5new.JPG|100px]]
|- style="height:75px"
! 22-23
| 17.5 || Knee, neck, eyelids
| [[file: 17.5new.JPG|100px]]
|- style="height:75px"
! 23
| 18.5 || Hands and feet join at the midline, closure of abdominal wall, eyelids cover eyes
| [[file: 18.5new.JPG|100px]]
|-
| colspan="4" align="center"| Following this stage fetal appearance is completed, organogenesis is achieved
|}

==Genetics==

===Sequencing===
The National Human Genome Research Institute selected the European rabbit (Oryctolagus cuniculus) for whole genome sequencing to enhance their understanding of the human genome and use it experimentally for an animal model for human disease. (8)

The rabbit has been sequenced twice by The Broad Institute as part of the mammalian genome project. It is now currently undergoing 7 more sequencing projects. Its sequencing is made by the Whole Genome Shotgun (WGS) and assembly method. (9) This is when genomic DNA is sheared into small pieces of approximately 2000 base pairs which are then cloned into plasmids and sequenced on both strands. Once the contig fragments are read, realigned and reassembled by computer algorithms, it will give the overall sequence. (10) (11) The image below shows diagramatically how the two types of sequencing are different. The same techniques are used for sequencing the human genome (in 2003). [A contig is a set of overlapping DNA segments, derived from a single source of genetic material, from which the complete sequence may be deduced.

The whole genome shotgun (WGS) has serious gaps, yet the information has already proven useful for immunological as well as in silico studies. Deeper 7x coverage started in September 2007. The NCBI Rabbit Genome Resources site has links to searches for genes in the assemblies of the 2x WGS sequence at Ensembl and UCSC.(12) [http://www.broadinstitute.org/models/europeanrabbit/ Rabbit Genome Project]

[[File:WGS_sequencing.gif‎|center|800 px]]

===Genome===
The Rabbit genome was published by two groups (9)
# Lindblad-Toh,K., Chang,J.L., Gnerre,S., Clamp,M. and Lander,E.S. published their admission of 84024 bases on May 5th 2005 to The Broad Institute (USA) by shotgun sequencing
# Di Palma,F., Heiman,D., Young,S., Gnerre,S., Johnson,J., Lander,E.S. and Lindblad-Toh,K. published their admission of 84024 bases on August 3rd 2009 to The Broad Institute (USA) by shotgun sequencing.
The rabbit's genome is sequenced and on display in the Nucleotide Data Bank. It is too long to produce here. A link to the data bank is provided: [http://www.ncbi.nlm.nih.gov/nuccore/256946799/ Rabbit Genome from the Nucleotide Data Bank]

[[File:8cellembryo.jpg|thumb|Individual mitochondria (arrowheads) of an 8cell Rabbit embryo]]

The rabbit genome was sequenced in 2005 by Ensembl and managed to produce: (13)
* 2,076,044,328 supercontigs (ordered Contigs with gaps)
* 495 Known protein-coding genes
* 11,357 Projected protein-coding genes
* 2,343 RNA genes
* 212,581 Gene exons
* 20,311 Gene transcripts

For further research the taxonomy ID number for the Rabbit is: 9986 [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=9986&lvl=3&lin=f&keep=1&srchmode=1&unlock/ Taxonomy Data]

===Mitochondrial Genome===
The mitochondiral genome (mtDNA) of the rabbit was sequenced on November 14th 2006 with 17245 base pairs/nucleotides in circular form. Apparently the "length is not absolute due to the presence of different numbers of repeated motifs in the control region".
PMID 9653643

The image to the right shows the mitochondria during cell division and multiplication in embryo development.

=== Chromosomes ===
Over the years there have been various data suggesting the diploid chromosomal number for the rabbit may range from 22-42. However through recent research and an abundance of trials suggest that the rabbit does indeed have 22 different chromosome pairs existing in each cell of the rabbit. (16)(17) The sex chromosomes of the rabbit are of X-Y type convincingly (17). In a study in Bombay it confirmed that a rabbit has 2n = 44 chromosomes. There were 21 pairs of autosomes, out of which 1 to 6 were metacentric, 7 to 11 submetacentric, 12 to 17 subtelocentric and 18 to 21 acrocentric, plus the sex chromosomes. The image to the left shows a female rabbit with no chromosomal abnormalities. (19)

'''Comparison to human chromosome:'''

Rabbit chromosomes 12, 19 and X were found to be completely homologous to human chromosomes 6, 17 and X, respectively. All other human chromosomes were homologous to two or sometimes three rabbit chromosomes. (14) Chromosome 12 was shorter than chromosomes 13 and 14. (15) The image below illustrates the human chromosome (2n = 46).

[[File:Drawn chromosome.jpg|left|400 px]]

[[File:Karyotypehuman.gif|right|500 px]]

'''Abnormalities'''

These are generally more apparent during early embryo development in blastocysts from delayed fertilization. Some examples of abnormal development include cases of: (18)
* hypoploidy; 1 chromosome missing from a pair (2n = 43),
* double hypoploidy; 2 chromosomes missing from 2 different pairs (2n = 42),
* mosaicism (different chromosomal makeup in some cells).

Another study also found these abnormalities as well as: (19)
* autosomal trisomy (3 autosomes per pair),
* triploidy (extra set of chromsomes),
* mixoploidy (unequal number of chromosome sets in adjacent cells), and
* short arm deletion (deletion of parts of chromosomes).

A specific abnormality occurring in rabbits is the x-linked tremor. There is a mutation in exon 2 of the prteolipid-protein (PLP 1) gene, corresponding to the end of the first potential transmembrane domain of the protein. This disorder affects myelination of the central nervous system. OMIA ID:12 [http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=full_report&list_uids=100009169&log$=omiamaingene| Gene:100009169]

==Abnormal Development==

Abnormal embryological development is a vast field of study that has been the subject of recent research papers. Our investigation of abnormal development in rabbit embryology will focus on abnormalities commonly found in both rabbit and human embryos. We will explore the nature of these abnormalities in both humans and rabbits.

[[File:Normal v Abnormal.jpg|right|300 px|thumb|Brain MRI of patient with Hydrocephalus (left) compared to a normal brain (right). An obvious increase in ventricular size and a significant decrease in brain size is present.]]
[[File:Ventricle_Expansion.jpg|right|300 px|thumb|CSF accumulation in ventricles of brain increasing intracranial pressure.The pressure from the expanding ventricles force the brain and skull to grow outwards abnormally.]]

'''Hydrocephalus'''

Annually, one in every 1000 children born in Australia have hydrocephalus. Hydrocephalus occurs when excessive cerebrospinal fluid (CSF) accumulates in the brain and can result in severe disability and even death because the disorder can result in complete or near complete destruction of the cerebral cortex (22).

Children born with hydrocephalus typically exhibit abnormally large head circumference and bulging cranial fontanels as a result of increased intracranial pressure on the brain from the accumulating CSF (22,23). As CSF accumulates in the ventricles and CSF compartments of the brain, it expands forcing the brain to grow outward. The outward growing brain places pressure on the skull which in turn also grows outwards giving rise to an abnormally large head circumference and bulging cranial fontanels (22,24). It is generally acknowledged that children with hydrocephalus have mental retardation, often to the degree of being “vegetative” (24).

The serious consequences of this disease mean that much research is necessary to unearth methods of prevention and effective treatment. One of the modes of studying hydrocephalus is to use the rabbit experimental model where hydrocephalus can be induced in rabbit embryo’s. The injection of silicone oil into the cisterna magna of the brain is one way of inducing hydrocephalus in the rabbit embryo. The silicone oil obstructs the normal flow of CSF resulting in CSF accumulation in the brain leading to hydrocephalus (25). Another method of inducing hydrocephalus in rabbit embryo’s is by intentional vitamin A deprivation of pregnant dams. The vitamin A deficiency results in raised intracranial CSF pressure and aqueduct stenosis causing poor circulation of CSF leading to hydrocephalus (26,27). Although the exact function of vitamin A on brain development and CSF regulation is not fully understood, it is clear that Vitamin A has an important role in brain development and its normal functioning (27).
[[File:Rabbithhdrocephalus.jpg|center|300 px|thumb|Young rabbit with hydrocephalus caused by Vitamin A deficiency. Note the abnormally shaped cranium inflamed in appearance.]]

[[File:SpinabifidaMeningocele1.jpg|right|300 px|thumb|Spina Bifida Meningocele has characteristic damage to the meninges of the spinal cord which are pushed out through an opening in the vertebrae as a cyst filled with CSF.]]
[[File:SpinaBifidaMyelomeningocele.jpg|right|300 px|thumb|Spina Bifida Myelomeningocele is the most severe form of spinabifida where the damaged spinal cord protrudes out with damaged meninges as a cyst filled with CSF.]]
[[File:SpinaBifidaOcculta1.jpg|right|300 px|thumb|Spina Bifida Occulta is the least severe as the spinal cord and meninges are undamaged.]]

'''Spina Bifida'''

In Australia, the risk of spina bifida is 1 in every 500 pregnancies. Spina bifida is a type of neural tube defect where vertebrae (which normally cover and protect the spinal cord) are not completely formed but are divided resulting in the defective spinal cord and its coverings to protrude through the opening (28,29).

There are three main types of Spina Bifida differentiated by their characteristic features:

1)Spina Bifida Meningocele characterized by normal spinal cord, divided outer vertebrae and meninges surrounding the spinal cord protruding from the divided vertebrae as a cyst (1,28).

2)Spina Bifida Myelomeningocele characterized by split outer vertebrae with spinal cord and its meninges protruding from the divided vertebrae as a cyst. Commonly found at lumbar vertebral level (1,28,29).

3)Spina Bifida Occulta characterized unfused vertebral arches and exposed vertebral canal. Spinal cord and its meninges still located in vertebral canal (1,28).

All forms of spina bifida are potentially fatal and in those where the spinal cord is damaged severe consequence arise including and paralysis and loss of sensation at and below the level of damage spinal cord damage (29,33). There is a lot of Spina bifida research using rabbit models to test the effective methods of correcting spina bifida. The occurrence of natural spina bifida in rabbits is rare and for experimental purposes it can be surgically created in rabbit fetuses during gestation (31,32). The process involves aesthetical sedation of the maternal rabbit at day 22 of gestation; a midline laparotomy performed and the desired type of spina bifida lesion created on the exposed fetus using forceps. Different methods for correcting spina bifida can then be tested and its effectiveness analysed (30,33,34).
[[File:Rabbitspinabifida1.jpg|center|350 px|thumb|Rabbit newborn with Spina Bifida. Note the unfused, divided vertebrae and exposed spinal cord.]]

'''Brachydactylia & Acheiropodia'''

[[File:Malformation1.jpg|right|150 px|thumb|Acheiropodia in rabbit characterized by amputations of the limbs and extremities.]]

[[File:Rabbitmalformation3.jpg|left|150 px|thumb|X-Ray study of rabbit limbs with malformed phalanges due to Brachydactylia.]]

Brachydactylia and Acheiropodia are genetic disorders characterized by skeletal malformation of the hands and feet (36,36). In Brachydactylia, the malformations commonly involve abnormal shortening of fingers and toes due to poorly formed or absent bones (35). Acheiropodia is characterized by more severe skeletal malformations including bilateral amputations of the distal upper and lower extremities as well as aplasia of the hands and feet. Although it is not fatal, the individual endures a very difficult life without hands and feet (37).

The inheritance mechanism of this diseases can has been studied through experiment using rabbits. Rabbits with abnormal genes coding for Brachydactylia and Acheiropodia are selected and bred to produce offspring with the disease (36). Brachydactylia and Acheiropodia are autosomal recessive disorders which means that two copies of an abnormal gene must be present in the affected individual in order for the disease to develop. Thus, each parent passes an abnormal gene to the offspring (35,36). The process of the malformation progresses from genotype to phenotype; small deletions on the chromosomes produce abnormal genes, the abnormal genes are then passed down to the offspring, the offspring that inherits two of the abnormal genes is unable to code for the correct proteins and as a result, there is failure in normal development of limb extremities in the embryo phenotype (37,38).

==Current Embryology Research==

There is currently great excitement in research involving rabbits in the fields of transgenesis, cloning and stem cells. We shall explore research in these areas by discovering some of the techniques used and how they have been applied to the rabbit model.

[[File:Trans1.jpg|right|170 px]]
[[File:Trans2.jpg|right|170 px]]
[[File:Trans3.jpg|right|170 px]]
[[File:Trans4.jpg|right|170 px]]
[[File:Trans5.jpg|right|170 px]]

'''Transgenic rabbit'''

A transgenic organism is one whose genome also contains genes from another species (39). The aim of creating a transgenic organism is to obtain a favorable characteristic in the organism’s phenotype (41). This desired characteristic of phenotype is obtained by altering the organism’s normal genotype to include the gene from another species with the desired characteristic (39,40).

The production of a transgenic organism involves several steps summarized below:

1) The chromosome and the desired gene on it are identified in an organism (39).

2) The gene is isolated from its DNA strand. This involves “cutting” it out of its DNA strand using enzymes called restriction endonucleases. The restriction endonucleases cut DNA at specific site so the desired gene can be removed from the DNA strand. The cut ends are known as “sticky ends” (39,40).

3) Separate DNA sequences for regulation sometimes have to be added to ensure the gene will work (40).

4) The gene is then inserted with a promoter sequence into the fertilized egg cell of a new organism producing recombinant DNA (39,44). To do this, firstly the new organism’s cell DNA must first be cut and the desired gene incorporated into it. The same enzymes are used to cut the new organism’s cell DNA because the DNA stands from the two different organisms will form matching sticky ends that will be attracted to and connect with each other in a process is called “annealing” (39,40,44).

5) DNA ligases are sealing enzymes found in all living organisms that help make and repair DNA (39,40). The DNA ligases are added to the annealed DNA fragments to help strengthen the bonds of the new recombinant DNA. The recombinant DNA is now transferred into the new organism’s fertilized egg by microinjection (44).

6) As the embryo develops and the recombinant genetic code read, new proteins are synthesized which code for the new desired phenotype characteristic in the transgenic organism (39,40).

Transgenic rabbits can be created in the laboratory by gene microinjection into the fertilized rabbit oocyte (44). In April 2000, a transgenic rabbit named Alba was born containing a gene from a Pacific Northwest jellyfish. The gene which was injected into a fertilized albino rabbit oocyte allows the rabbit to synthesize the green fluorescent protein (GFP) that is characteristic of the Pacific Northwest jellyfish. When illuminated correctly, Alba glows a bright green (43,46).

Transgenic rabbits have important research purposes. Transgenic rabbits can be created to model retinal degeneration (44). Retinal degeneration is a common problem with aging and diseases such as diabetes, and frequently leads to complete blindness (42). A genetic retinal degeneration disease called retinitis pigmentosa (RP) is created in these rabbits by introducing the “Pro347Leu” mutation of the rhodopsin gene into fertilized rabbit eggs (43,44). As the rabbit grows, it develops the disease which becomes progressively worse (45).
The use of these transgenic rabbits ultimately leads to better understanding of the disease and more effective treatments (42). [[File:Transgenic rabbit.jpg|center|250 px|thumb|"Alba" A trangenic rabbit with a gene from a Pacific Northwest jellyfish that allows it to synthesize the green fluorescent protein (GFP) of the jellyfish.]]

[[File:Crabbit 1.jpg|right|170 px]]
[[File:Rabbit2.jpg|right|170 px]]
[[File:Rabbit3.jpg|right|170 px]]
[[File:Crabbit 4.jpg|right|170 px]]

'''Cloning'''

Cloning is a method of producing genetically identical organisms. The principle of cloning relies on “tricking” an egg cell to begin rapidly dividing into an embryo (39). In the normal fertilization process, two haploid sex cells unite to form a diploid zygote which begins rapidly dividing into an embryo (40). By replacing the haploid egg cell nucleus with a diploid somatic cell nucleus, the egg cell is tricked into thinking it is fertilized and hence begins rapidly dividing to form an embryo (39,40,41).

The process of cloning involves several steps summarized as the following using a rabbit example:

1) A somatic cell is obtained from a rabbit and the nucleus removed (39).

2) An egg cell is obtained from a donor rabbit and the nucleus of the egg cell removed using an enucleation needle. The cell is now called an enucleated egg cell (egg cell without a nucleus) (39,41).

3) The nucleus of the somatic cell is inserted into the enucleated egg cell (41).

4) The cell is now stimulated to divide by applying pulses of electric current (39).

5) The rapidly dividing cell develops in culture for a few days forming the early embryo (40,41).

6) The embryo is then implanted into the uterus of another rabbit similar to the egg cell donor. This rabbit is called the surrogate mother (40,41).

7) The embryo develops and the surrogate mother gives birth to a rabbit fetus with near identical genotype of the somatic cell donor (the small genomic difference is caused by the fetus obtaining mitochondrial DNA from the egg cell donor) (39,41).

The cloning of rabbits has been achieved by inserting the diploid nucleus of a rabbit fibroblast (the principal cells in connective tissue) into an enucleated oocyte (49). There is currently much focus on the creation of controversial but revolutionary interspecies hybrid embryos where the nucleus from a human somatic cells are implanted into an enucleated egg cell of another animal (50). The resulting embryo (known as a chimera) will be almost completely human genotype but will have genome from the other animal (48). In 2003, scientists at the Shanghai Second Medical University fused human cell with rabbit eggs creating the first human-rabbit hybrid using the nucleus transfer technique. The hybrid embryo developed in culture for a few days before it was destroyed and the stem cells harvested (47,48). The purpose of the research into creating hybrid embryos is to provide researchers with human stem cells for experimentation into cures for diseases such as cystic fibrosis, Alzheimer’s and Motor Neuron disease as human stem cell are difficult to obtain (50).

[[File:Rabbit clone.jpg|center|450 px|thumb|(A) Cloned rabbits (5 month old) from nuclear transfer technique. (B) The male rabbit whose fibroblasts were used as the nuclear donors. The cloned rabbits have almost identical genome to the male donor.]]

'''Stem Cells'''
[[File:HES.jpg|right|200 px|thumb|Human Embryonic Stem cell (hES).]]
[[File:Rabbit knee.jpg|right|200 px|thumb|Stem cell induced cartilage repair of knee in rabbit.]]

Stem cells are unspecialized cells which are able to continuously reproduce themselves and under appropriate conditions, differentiate into all the various specialized cells of the organism such as cardiac cells, neurons and blood cells (39,40). Adults have a small number of stem cells when compared to a developing embryo and the stem cell of an embryo more easily obtained (41). Human embryonic stem cells (hES) derived from the inner mass of the preimplantation blastocyst have the potential to differentiate into all cell types in the human body and thus are valued by researchers (50). However, due to ethical and political issues, the obtaining and experimentation on human embryonic stem cells is difficult and alternate means are needed as stem cell provides potentially new treatments for a range of diseases (54).

Rabbits can be used both in the obtaining of stem cell for experimentation and also as recipients of stem cells to cure diseases. The human-rabbit hybrid embryo provides a method of obtaining stem cells for experimentation and these stem cells possess many similar properties to human stem cells, including expression of surface markers, special growth requirements, capabilities of self renewal, formation of embryonic body and differentiation into cells of all three germ layers (53).

Stem cell experimentation on rabbits also focuses on transplanting stem cell into rabbits to treat specific diseases. A study at Zhejiang University where a research team transplanted human mesenchymal stem cell into New Zealand white rabbits with myocardial infarction recoded regeneration of vascular structure and improvement in cardiac function. The research team noted the potential of stem cells in differentiating into specialized cardiac cells when subjected to the specific conditions of the rabbit heart (52).

Another study at Hallym University tested the effectiveness of transplanting mesenchymal stem cells from New Zealand white rabbits into damaged cartilage in the knees of other New Zealand white rabbits. In the experiment, mesenchymal stem cells were obtained from the rabbit bone marrow and injected into the knees of other rabbits that had cartilage in their knees surgically damaged. The research team were able to conclude notable cartilage recovery in the rabbits with the mesenchymal stem cell injection and the potential of mesenchymal stem cells to differentiate into fibroblasts, adipoblasts, osteoblasts and chondroblasts (51,53).

The findings in stem cell experimentation with in rabbits yielded positive results and potentially opens a new field of research in the use of stem cell to treat a range of diseases in humans.

==References==

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# E.Horne Craigie, University of Toronto Press 1948, Bensley's Practical Anatomy of the Rabbit 8th Edition
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# Jocelyn HD, Setchell BP (December 1972). "Regnier de Graaf on the human reproductive organs. An annotated translation of Tractatus de Virorum Organis Generationi Inservientibus (1668) and De Mulierub Organis Generationi Inservientibus Tractatus Novus (1962)". Journal of Reproduction and Fertility. Supplement 17: 1–222.
# Jay, V. (2000). "A portrait in history. The legacy of Reinier de Graaf". Archives of Pathology & Laboratory Medicine 124(8): 1115–6.
# Lois N Magner. "A history of the Life Sciences" 3rd edition
# J. D. Biggers. (1991). Walter Heape, FRS: a pioneer in reproductive biology.Centenary of his embryo transfer experiments Laboratory of Human Reproduction and Reproductive Biology, and Department of Cellular and Molecular Physiology, Harvard Medical School, Boston, MA 02115, USA
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# Trivedi, B. (2000). ''Sequencing the Genome''. Retrieved September 4, 2009, from [http://www.genomenewsnetwork.org/articles/06_00/sequence_primer.shtml Shotgun Sequencing - 2]
# Mage, R. (2008). Rabbit genome sequencing update: genes of immunological interest found in the 2x genome assemblies, ENCODE, and the 7x trace archive. ''Journal of FASEB'' 22(Retrieved September 5, 2009, from [http://www.fasebj.org/cgi/content/meeting_abstract/22/2_MeetingAbstracts/559/ Rabbit Genome & its Immunological Interest]
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# Korstanje, R. et al. (1999) Complete homology maps of the rabbit (Oryctolagus cuniculus) and human by reciprocal chromosome painting. ''Cytogenetics and cell genetics'' ''86''(3-4), 317-322. Retrieved September 6, 2009, from [http://cat.inist.fr/?aModele=afficheN&cpsidt=1189693/ Complete homology maps of the rabbit Article] "PMID 10575232"
# Brunner, R., Knopp, A., Rudolph, W. (n.d). Rabbit chromosome analysis by image processing. ''Journal of Applied Rabbit Research''.
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# Painter, T. (2009) Studies in mammalian spermatogenesis VI. The chromosomes of the rabbit. ''Journal of Morphology''. ''43''(1): 1-43.
# Hofsaess, F., and Meacham, T. ( 1995) Chromosome abnormalities of early rabbit embryos. ''Journal of Experimental Zoology''. ''177'' (1): 9-11 [http://www3.interscience.wiley.com/journal/110490865/abstract/ Chromosome abnormalities]
# Martin-Deleon, P., Shaver, E., and Gammal, E. (1973) Chromosome abnormalities in rabbit blastocysts resulting from spermatozoa aged in the male tract. ''Fertility and Sterility''. ''24''(3):212-219.
# Patil, M. et al (2004) Chromosome analysis of domestic rabbit. ''The Journal of Bombay Veterinary College''. ''12'' (1 and 2)
#Biggers J.D (1991) Walter Heape FRS: a pioneer in reproductive biology. centenary of his embryo transfer experments.''Journals of reproduction and fertility''. ''93''(1)
# Stoodley, M (2006). Hydrocephalus. Prince of Wales Clinical School. Retrieved from [http://www.brainaustralia.org.au/AZ_of_Brain_Disorders/hydrocephalus]
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# Lewin, R (1999). Is Your Brain Really Necessary?. 24) Developmental Medicine & Child Neurology, 41. Retrieved from [http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=176431]
# Bigio, M.R, & Bruni J.E (1991). Silicone oil-induced hydrocephalus in the rabbit . Child's Nervous System, 7(2), Retrieved from [http://www.springerlink.com/content/b011477724837152/]
# Geelen, J.A (1974). A case of hydrocephalus and meningoencephalocele in a rabbit, caused by aqueductal malformation. Laboratory Animals, 8(2), Retrieved from [http://la.rsmjournals.com/cgi/content/abstract/8/2/167]
# LAMMINGX, G.E (1954). 27) Hydrocephalus in Young Rabbits Associated with Maternal Vitamin A Deficiency. British Journal of Nutrition, 8(2), Retrieved from [http://journals.cambridge.org/download.php?file=%2FBJN%2FBJN8_04%2FS0007114554000554a.pdf&code=10bb1dbc4a9e57a091f4e05f6aebbcf2]
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# Peeters, M.C, Viebahn, C, & Hekking, J.W (1998). Neurulation in the rabbit embryo . Anatomy and Embryology, 197(3), Retrieved from [http://www.springerlink.com/content/1efyteewgetjlwyg/]
# George, T.M, & Fuh E (2003). Review of Animal Models of Surgically Induced Spinal Neural Tube Defects: Implications for fetal surgery. Pediatric Neurosurgery , 39(2), Retrieved from [http://content.karger.com/produktedb/produkte.asp?typ=fulltext&file=PNE2003039002081]
# Pedreira, D.A, & Valente P.R (2002). A Different Technique to Create a 'Myelomeningocele-Like' Defect in the Fetal Rabbit. Fetal diagnosis and therapy, 17(6), Retrieved from [http://content.karger.com/ProdukteDB/produkte.asp?Doi=65388]
# Patten, B.M (1953). Embryological stages in the establishing of myeloschisis with spina bifida. The American journal of anatomy, 93(3), Retrieved from [http://deepblue.lib.umich.edu/handle/2027.42/49611]
# Pedreira, D.A, & Valente P.R (2003). Successful Fetal Surgery for the Repair of a 'Myelomeningocele-Like' Defect Created in the Fetal Rabbit. Fetal Diagnosis and Therapy, 18. Retrieved from [http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowPDF&ProduktNr=224239&Ausgabe=229041&ArtikelNr=69378]
# Lecklitner, M.L, & Douglas K.P (1986). Osteoscintigraphy and brachydactylia of the hand . European Journal of Nuclear Medicine and Molecular Imaging, 12(9), Retrieved from [http://www.springerlink.com/content/t82l77282x579102/]
# Greene, H.S, & Saxton J.A (1938). HEREDITARY BRACHYDACTYLIA AND ALLIED. ABNORMALITIES IN THE RABBIT. THE JOURNAL OF EXPERIMENTAL MEDICINE , 69. Retrieved from [http://jem.rupress.org/cgi/reprint/69/2/301.pdf]
# P. Ianakiev, M. van Baren, M. Daly, S. Toledo, M. Cavalcanti, J. Neto, E. Silveira, A. Freire-Maia, P. Heutink, M. Kilpatrick. Acheiropodia Is Caused by a Genomic Deletion in C7orf2, the Human Orthologue of the Lmbr1 Gene. The American Journal of Human Genetics, 68. Retrieved from [http://linkinghub.elsevier.com/retrieve/pii/S0002929707624707]
# Walbaum, R, Hazard, C, & Cordier, R (1976). Brachydactylia with symphalangism, probably autosomal recessive . Human Genetics, 33(2), Retrieved from [http://www.springerlink.com/content/m630p6880661486n]
# Campbell, N.A, & Reece, J.B (2002). Biology 6th Edition. USA: Benjamin Cummings.
# Solomon, E.P, Berg, L.R, & Martin, D.W (2002). Biology 6th Edition. USA: Thompson Learning.
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# Kondo, M, Sakai, T, & Ueno, S (2009). Generation of a Transgenic Rabbit Model of Retinal Degeneration. Investigative Ophthalmology and Visual Science, 50. Retrieved from [http://www.iovs.org/cgi]
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# Li, S, & Chen X (2006). Rabbits generated from fibroblasts through nuclear transfer . Society for Reproduction and Fertility, 131. Retrieved from [http://www.reproduction-online.org/cgi/reprint/131/6/1085]
# Minger, S (2007). Interspecies SCNT derived human embryos. Regenerative Medicine, 2(2), Retrieved from [http://www.futuremedicine.com]
# Koga, H, Shimaya, M, & Muneta, T (2008). Local adherent technique for transplanting mesenchymal stem cells as a potential treatment of cartilage defect. Arthritis Research & Therapy, 10(4), Retrieved from [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2575632]
# Wang, J, Li, C, & Sun, Y (2005). Human bone marrow-derived mesenchymal stem cells transplanted into damaged rabbit heart to improve heart function. Journal of Zhejiang University Science, 6(4), Retrieved from [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1389731]
# Chen, Y, Liu, A, & Mao, W (2003). Embryonic stem cells generated by nuclear transfer of human somatic nuclei into rabbit oocytes. Cell Research , 13(4), Retrieved from [http://www.nature.com]
# Bethesda (2009, September 23). Stem Cell Information. Retrieved from [http://stemcells.nih.gov]
# Cibelli, J. B. (2002). Principles of cloning Amsterdam. Academic Press
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# Warner, S. (2003). Inositol transport in preimplantation rabbit embryos: Effects of embryo stage, sodium, osmolality and metabolic inhibitors Reproduction, 125(4), 479-493.
# Derelanko, M. J. (2008). The toxicologist's pocket handbook, second edition Informa HealthCare
# Beaudoin, S., Barbet, P., & Bargy, F. (2003). Developmental stages in the rabbit embryo: Guidelines to choose an appropriate experimental model Fetal Diagnosis and Therapy, 18(6), 422-427.

==Glossary==

Anesthetic - A drug that causes temporary loss of bodily sensations

Aplasia - The absence or defective development of a tissue or organ

Blastocyst - A stage of embryo development that occurs about five days after fertilisation when the embryo contains quite a few cells

Caudal - Situated towards the inferior or posterior end of the body

Cephalic - Relating to the head

Cerebral Aqueduct - A canal filled with cerebrospinal fluid within the midbrain

Cerebral Cortex - The layer of unmyelinated neurons (the grey matter) forming the cortex of the cerebrum of the brain

Cerebro Spinal Fluid (CSF) - A watery fluid which flows in the cavities within the brain and around the surface of the brain and spinal cord

Chromosome - Microscopic carriers of genetic material, composed of deoxyribonucleic acid (DNA) and proteins and appearing as rods under a microscope

Cisterna Magna - is one of three principal openings in the subarachnoid space between the arachnoid and pia mater layers of the meninges surrounding the brain

Diploid - A full set of genetic material, consisting of paired chromosomes one chromosome from each parental set

Dorsal - Position towards the back

Fontanel - Membranous gap between the bones of the cranium in an infant or fetus

Genome - All genetic information, the entire genetic complement and all of the hereditary material possessed by an organism. Made up of both chromosomal genome (inside the nucleus of the cell in the familiar form of chromosomes) and mitochondrial genome (outside the nucleus in the cytoplasm of the cell, usually in the form of one round chromosome (the mitochondrial chromosome))

Genotype - The genetic makeup of an organism

Glucocorticoids - A class of steroid hormones that bind to the glucocorticoid receptor (GR), which is present in almost every vertebrate

Haploid - A single set of chromosomes (half the full set of genetic material)

Laparotomy- Surgical incision into the abdominal wall; often done to examine abdominal organs

Ligases - Group of enzymes that catalyze the binding of two molecules

Oocyte - A female gametocyte that develops into an ovum after two meiotic divisions

Phenotype - The observable traits or characteristics of an organism, for example hair color, weight, or the presence or absence of a disease.

Pronuclear - Haploid nucleus before fusion of nuclei in fertilisation

Restriction Endonucleases - Enzymes that recognize and cleave specific DNA sequences, generating either blunt or single-stranded (sticky) ends

Retina - The thin layer of cells at the back of the eyeball where light is converted into neural signals sent to the brain

Rostral - Situated toward the oral and nasal region

Somite - Blocks of mesoderm on either side of the notochord and neural tube during development of the vertebrate embryo. Develop into muscles and vertebrae

Stenosis - Abnormal narrowing of a bodily canal or passageway

Weaning - Young become accustom to nourishment other than suckling

==Links to Research Laboratories and Researchers==

1) Transgenic lab: [http://www.dnavision.be/index.php]

Involved in development of transgenic organisms, DNA construction and phenotype analysis.

2) World Rabbit Science Association: (WRSA) [http://world-rabbit-science.com]

International Association where researchers exchange knowledge and encourage teaching, scientific research, practical experimentation, the collection and publication of statistics and documents relating to the rabbit. Even have their own journal called “World Rabbit Science”

Website provides contact with researchers, professors and veterinarians working with rabbits.

Example: Dr. Myriam Kaplan-Pasternak, Doctorate Veterinary Medicine, University of California, myriamsemail@gmail.com

3) American Veterinary Medical Association [http://www.avma.org]

The American Veterinary Medical Association (AVMA), established in 1863, is a not-for-profit association representing more than 78,000 veterinarians working in private and corporate practice, government, industry, academia, and uniformed services. Excellent website into animal research and has a range of veterinary journals.

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== '''THE RABBIT (ORYCTOLAGUS CUNICULUS)''' ==

==Introduction==

[[File:Isidro_Martinez.jpg‎|left|175 px]]

Several characteristics of the rabbit make it an excellent model for study. This will be further explored in "The History of Model Use" section of this page. Many studies have resulted in the development and improvement of various micro-manipulation techniques such as the production of transgenic rabbits. Unlike many other species such as the chick or rat, relatively little is known about the development of a rabbit. Nevertheless, it is still an appropriate animal model as the results from many experiments are significant to that of other mammals, including humans. (55)

A rabbits potential for reproduction is high, breeding from the early stages of 3 to 4 months of age. A mature female rabbit can be pregnant from 6 to 8 months in a year, producing up to 30 to 40 young in this time. (56)

==History of Model Use==

'''WHY are we using rabbits?'''

ADVANTAGES
*Provides repeatability of animal model studies
*Large enough for single samples
*Many stocks/strains as animal models
*Easily managed
*Quality of immunologic products
*Ease of reproductive control

DISADVANTAGES
*Most colonies are a storehouse of diseases
*Extremely variable to responses to general anesthetics

'''Brief timeline of rabbit embryo model use'''

*1672- de Graaf found the Graffian follicle.
*1890- Walter Heape succeeded first mammalian embryo transfer
*1906- FT Lewis discovered the development of the lymphatic system in rabbit embryos.
*1941- Dr. Pincus succeeded in keeping rabbit embryos developing in the test
*1968- Edwards and Gardner successfully performed the first known embryo biopsy on rabbit embryos

=== Regnier de Graaf (1641–1673) ===
[[image:Ovary_Graaf.jpg|thumb|250px|left|drawing of ovary]]
[[File:Regnier de Graaf.jpg|right]]

'''Discovery of the Graafian Follicles'''

In 1672 de Graaf published ''The Generative Organs of Women'', which was primarily a study of development in the rabbit. When de Graaf discovered large, round welling on the ovaries of rabbits, he assumed they were mammalian eggs. De Graaf also described the corpus luteum.

He summarised the previous works from anatomists, but unable to experience the amazing benefits made by microscopy.
But Antonie van Leeuwenhoek (A microbiologist, 1632 - 1723) argued that the structures now known as Graafian follicles could not be eggs. Haller suggested that the egg might be formed by the coagulation of the fluid within the Graafian follicle. De Graaf noted that the “egg” did not contain a tiny embryo, but he thought it did contain the “germ” of the future organism. (3)

=== Walter Heape (1855-1928) ===
'''First case of embryo transfer experiments'''

On 27 April 1890, Walter Heape (a professor and physician at the University of Cambridge, England) transferred rabbit embryos from one mother to another. (7) One rabbit mother became pregnant and delivered young from the transferred embryos. This was the first mammalian embryo transfer experiment to be successfully completed. His embryo transfer work in perspective as it relates to other contributions of this pioneer in reproductive biology.(7)

In 1891, Walter Heape had been conducting research on reproduction in numerous animal species. Working with two species of rabbits, he flushed embryos from the rabbit fallopian tubes of one breed (Angora) and placed them into the uterus of a recently mated Belgian hare. In the resulting litter, there were 4 Belgians and 2 Angoras. Heape proved that it was possible to take preimplantation embryos and transfer them to a gestational carrier without affecting their development.(7)

===Dr. Gregory Goodwin Pincus (1903-1967) ===

'''Contraceptive pill'''

Dr. Pincus began studying hormonal biology and steroidal hormones early in his career. His first breakthrough came when he was able to produce in vitro fertilization in rabbits (by using chemicals) in 1934. Throughout their hormonal contraceptive research Pincus, along with reproductive physiologist Min Chueh Chang, found out progesterone would act as an inhibitor to ovulation. They co-invented the combined oral contraceptive pill.[2][6]

===Genetic Diagnosis===
In 1968, Robert Edwards and David Gardner reported the successful sexing of rabbit blastocysts, setting the first steps towards PGD (Preimplantation Genetic Diagnosis). It was not until the 1980s that human IVF was fully developed, which coincided with the breakthrough of the highly sensitive polymerase chain reaction (PCR) technology. Handyside and collaborators' first successful attempts at testing were in October 1989 with the first births in 1990 though the preliminary experiments had been published some years earlier. In these first cases, PCR was used for sex determination for patients carrying X-linked diseases.(12)

==Timeline of Embryo Development==

The following is a timeline, adapted from Cibelli (2002), of the main events of preimplantation development in rabbits. The time is measured in hours post-mating and shows the embryo stage (cell number) in each time scale.

[[File:Morula1.JPG|right|200 px|thumb|A day 2 early morula]]

'''12-14 hours:''' Oocyte; Fertilization

'''18-20 hours:''' Zygote; Pronuclear formation

'''24-26 hours:''' Two cell

'''30-32 hours:''' Four cell

'''38-40 hours:''' Eight cell; Maternal-zygotic transition

'''46-48 hours:''' Sixteen cell

'''54-56 hours:''' Morula (32 cell); Compaction and transport to uterus

'''64-66 hours:''' Compact morula (64 cell); Morula-blastocyst transition

'''76-78 hours:''' Early blastocyst (128 cell)

'''84-86 hours:''' Expanded blastocyst (256 cell); Blastocoels expansion

'''94-96 hours:''' Hatched blastocyst (512 cell); Hatching

The following shows a diagrammatic representation of the relative sizes of rabbit embryos. The sizes do not include the embryonic coverings such as the zona pellucida and mucin coat. This diagram has been adapted from Warner (2003).

[[File:Sizes.JPG]]

The following timelines show a comparison of the developmental stages between human and rabbit embryos. They have been adapted from Derelanko (2008). "The similarities of this developmental pattern in humans and rabbits, suggests that the same growth increment is required to achieve the same stage. The main difference observed between human rabbit gestational duration is due to the fetal growth phase. The reason for this may be due to birth weight, lifetime and the neural complexity of the species." (59)

[[File:Timeline_rabbit.JPG]]

The following timelines have been adapted from a study carried out by Beaudoin et al. on the development of rabbit embryos.

==='''Body Form'''===

'''8.5 days''': Embryo thickens. First somites appear. Rostral neuropore closes. Caudal neuropore remains open

'''9.5 days''': Dorsal curvature begins. Cardiac mass bulges under cephalic pole.

'''10.5 - 13.5 days''': Dorsal curvature increases. Body thickens. Softening of the cephalic domination straightens the embryo.

'''17.5 days''': Neck becomes visible.

==='''Limb Development'''===

''' 9.5 days''': Rostral limb bud appears

'''10.5 days''': Caudal limb bud appears

'''12.5 days''': Hand plate becomes present. Limbs become disposed.

'''13.5 days''': Foot plate and finger rays become visible.

'''14.5 days''': Rostral and caudal limbs become parallel.

'''15.5 days''': Elbow appears.

'''16.5 days''': Fingers start to elongate.

'''17.5 days''': Knee becomes visible

'''19.5 days''': Hands and feet merge on the midline. Three segments of limbs become distinguished.

==='''Abdominal Wall Development'''===

'''9.5 days''': Abdominal wall is limited to the embryonic pedicle under the cardiac mass.

'''13.5 days''': First intestinal loops appear in the umbilical cord.

'''14.5 days – 17.5''': Rapid intestinal development in the cord.

'''15.5 days''': Abdominal vesicles can be observed.

'''16.5 days''': Cecal bud becomes present outside the abdomen

'''18.5 days''': Bowel returns to the abdominal cavity and umbilical ring closes.

==='''Cephalic Development'''===

'''9.5 days''': One cerebral vesicle can be seen. Pharyngeal arches as optic vesicle are present.

'''10.5 days''': Three arches are distinguished in the cephalic pole.

'''11.5 days''': Three cerebral vesicles present. Optic plate is distinguished.

'''12.5 days''': Face develops nasal, maxillar and mandibular buds. Lens vesicle is closed. Five cerebral vesicles exist.

'''14.5 days''': The ear becomes refined. Face can be distinguished from the brow.

'''18.5 days''': Eyelid appears, covering the eyes.

==Staging==

The following stages have been adapted from Beaudoin et al. (2003). Table 1 represents at each age its corresponding stage defined by the Carnegie classification

{| class="wikitable" style="text-align:center; width: 800px; height:1000px" border="1"
|+'''Table 1. Rabbit developmental stages using Carnegie classification'''

|- style="height:50px"
! '''Stage''' !! '''Days''' !! '''Event''' !! '''Image'''
|- style="width:200px"
! width="50" | 10
| width="50" | 8.5 || First somites appear, rostral neuropore closes
|- style="height:75px"
! 12
| 9.5 || Rostral limb bud, embryonic pedicle, caudal neuropore closes, one cerebral vesicle, pharyngeal arches, completion of optic vesicle
| [[file: 9.5new.JPG|100px]]
|- style="height:75px"
! 13
| 10.5 || Dosral C-shaped curvature, caudal limb bud, prominent cardiac swelling, four pharyngeal arches
| [[file: 10.5new.JPG|100px]]
|- style="height:75px"
! 14
| 11.5 || Three cerebral vesicles, optic plate, mesonephric ridge
|- style="height:75px"
! 15
| 12.5 || Hand plate, wheel ray limbs, lens vesicle closes, five cerebral vesicles, facial buds, vertebrae
| [[file: 12.5new.JPG|100px]]
|- style="height:75px"
! 16
| 13.5 || Foot plate, finger rays, prominent liver, intestinal loops, auricular hillocks
| [[file: 13.5new.JPG|100px]]
|- style="height:100px"
! 19
| 14.5 || Cuboidal body, trunk straightens, parallel limbs, toe rays, modeled face, visible auricle
| [[file: 14.5new.JPG|100px]]
|- style="height:75px"
! 20
| 15.5 || Elbow, fingers elongate, notches between toe rays
| [[file: 15.5new.JPG|100px]]
|- style="height:75px"
! 21-22
| 16.5 || Toes free, cecal bud in intestinal hernia
| [[file: 16.5new.JPG|100px]]
|- style="height:75px"
! 22-23
| 17.5 || Knee, neck, eyelids
| [[file: 17.5new.JPG|100px]]
|- style="height:75px"
! 23
| 18.5 || Hands and feet join at the midline, closure of abdominal wall, eyelids cover eyes
| [[file: 18.5new.JPG|100px]]
|-
| colspan="4" align="center"| Following this stage fetal appearance is completed, organogenesis is achieved
|}

==Genetics==

===Sequencing===
The National Human Genome Research Institute selected the European rabbit (Oryctolagus cuniculus) for whole genome sequencing to enhance their understanding of the human genome and use it experimentally for an animal model for human disease. (8)

The rabbit has been sequenced twice by The Broad Institute as part of the mammalian genome project. It is now currently undergoing 7 more sequencing projects. Its sequencing is made by the Whole Genome Shotgun (WGS) and assembly method. (9) This is when genomic DNA is sheared into small pieces of approximately 2000 base pairs which are then cloned into plasmids and sequenced on both strands. Once the contig fragments are read, realigned and reassembled by computer algorithms, it will give the overall sequence. (10) (11) The image below shows diagramatically how the two types of sequencing are different. The same techniques are used for sequencing the human genome (in 2003). [A contig is a set of overlapping DNA segments, derived from a single source of genetic material, from which the complete sequence may be deduced.

The whole genome shotgun (WGS) has serious gaps, yet the information has already proven useful for immunological as well as in silico studies. Deeper 7x coverage started in September 2007. The NCBI Rabbit Genome Resources site has links to searches for genes in the assemblies of the 2x WGS sequence at Ensembl and UCSC.(12) [http://www.broadinstitute.org/models/europeanrabbit/ Rabbit Genome Project]

[[File:WGS_sequencing.gif‎|center|800 px]]

===Genome===
The Rabbit genome was published by two groups (9)
# Lindblad-Toh,K., Chang,J.L., Gnerre,S., Clamp,M. and Lander,E.S. published their admission of 84024 bases on May 5th 2005 to The Broad Institute (USA) by shotgun sequencing
# Di Palma,F., Heiman,D., Young,S., Gnerre,S., Johnson,J., Lander,E.S. and Lindblad-Toh,K. published their admission of 84024 bases on August 3rd 2009 to The Broad Institute (USA) by shotgun sequencing.
The rabbit's genome is sequenced and on display in the Nucleotide Data Bank. It is too long to produce here. A link to the data bank is provided: [http://www.ncbi.nlm.nih.gov/nuccore/256946799/ Rabbit Genome from the Nucleotide Data Bank]

[[File:8cellembryo.jpg|thumb|Individual mitochondria (arrowheads) of an 8cell Rabbit embryo]]

The rabbit genome was sequenced in 2005 by Ensembl and managed to produce: (13)
* 2,076,044,328 supercontigs (ordered Contigs with gaps)
* 495 Known protein-coding genes
* 11,357 Projected protein-coding genes
* 2,343 RNA genes
* 212,581 Gene exons
* 20,311 Gene transcripts

For further research the taxonomy ID number for the Rabbit is: 9986 [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=9986&lvl=3&lin=f&keep=1&srchmode=1&unlock/ Taxonomy Data]

===Mitochondrial Genome===
The mitochondiral genome (mtDNA) of the rabbit was sequenced on November 14th 2006 with 17245 base pairs/nucleotides in circular form. Apparently the "length is not absolute due to the presence of different numbers of repeated motifs in the control region".
PMID 9653643

The image to the right shows the mitochondria during cell division and multiplication in embryo development.

=== Chromosomes ===
Over the years there have been various data suggesting the diploid chromosomal number for the rabbit may range from 22-42. However through recent research and an abundance of trials suggest that the rabbit does indeed have 22 different chromosome pairs existing in each cell of the rabbit. (16)(17) The sex chromosomes of the rabbit are of X-Y type convincingly (17). In a study in Bombay it confirmed that a rabbit has 2n = 44 chromosomes. There were 21 pairs of autosomes, out of which 1 to 6 were metacentric, 7 to 11 submetacentric, 12 to 17 subtelocentric and 18 to 21 acrocentric, plus the sex chromosomes. The image to the left shows a female rabbit with no chromosomal abnormalities. (19)

'''Comparison to human chromosome:'''

Rabbit chromosomes 12, 19 and X were found to be completely homologous to human chromosomes 6, 17 and X, respectively. All other human chromosomes were homologous to two or sometimes three rabbit chromosomes. (14) Chromosome 12 was shorter than chromosomes 13 and 14. (15) The image below illustrates the human chromosome (2n = 46).

[[File:Drawn chromosome.jpg|left|400 px]]

[[File:Karyotypehuman.gif|right|500 px]]

'''Abnormalities'''

These are generally more apparent during early embryo development in blastocysts from delayed fertilization. Some examples of abnormal development include cases of: (18)
* hypoploidy; 1 chromosome missing from a pair (2n = 43),
* double hypoploidy; 2 chromosomes missing from 2 different pairs (2n = 42),
* mosaicism (different chromosomal makeup in some cells).

Another study also found these abnormalities as well as: (19)
* autosomal trisomy (3 autosomes per pair),
* triploidy (extra set of chromsomes),
* mixoploidy (unequal number of chromosome sets in adjacent cells), and
* short arm deletion (deletion of parts of chromosomes).

A specific abnormality occurring in rabbits is the x-linked tremor. There is a mutation in exon 2 of the prteolipid-protein (PLP 1) gene, corresponding to the end of the first potential transmembrane domain of the protein. This disorder affects myelination of the central nervous system. OMIA ID:12 [http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=full_report&list_uids=100009169&log$=omiamaingene| Gene:100009169]

==Abnormal Development==

Abnormal embryological development is a vast field of study that has been the subject of recent research papers. Our investigation of abnormal development in rabbit embryology will focus on abnormalities commonly found in both rabbit and human embryos. We will explore the nature of these abnormalities in both humans and rabbits.

[[File:Normal v Abnormal.jpg|right|300 px|thumb|Brain MRI of patient with Hydrocephalus (left) compared to a normal brain (right). An obvious increase in ventricular size and a significant decrease in brain size is present.]]
[[File:Ventricle_Expansion.jpg|right|300 px|thumb|CSF accumulation in ventricles of brain increasing intracranial pressure.The pressure from the expanding ventricles force the brain and skull to grow outwards abnormally.]]

'''Hydrocephalus'''

Annually, one in every 1000 children born in Australia have hydrocephalus. Hydrocephalus occurs when excessive cerebrospinal fluid (CSF) accumulates in the brain and can result in severe disability and even death because the disorder can result in complete or near complete destruction of the cerebral cortex (22).

Children born with hydrocephalus typically exhibit abnormally large head circumference and bulging cranial fontanels as a result of increased intracranial pressure on the brain from the accumulating CSF (22,23). As CSF accumulates in the ventricles and CSF compartments of the brain, it expands forcing the brain to grow outward. The outward growing brain places pressure on the skull which in turn also grows outwards giving rise to an abnormally large head circumference and bulging cranial fontanels (22,24). It is generally acknowledged that children with hydrocephalus have mental retardation, often to the degree of being “vegetative” (24).

The serious consequences of this disease mean that much research is necessary to unearth methods of prevention and effective treatment. One of the modes of studying hydrocephalus is to use the rabbit experimental model where hydrocephalus can be induced in rabbit embryo’s. The injection of silicone oil into the cisterna magna of the brain is one way of inducing hydrocephalus in the rabbit embryo. The silicone oil obstructs the normal flow of CSF resulting in CSF accumulation in the brain leading to hydrocephalus (25). Another method of inducing hydrocephalus in rabbit embryo’s is by intentional vitamin A deprivation of pregnant dams. The vitamin A deficiency results in raised intracranial CSF pressure and aqueduct stenosis causing poor circulation of CSF leading to hydrocephalus (26,27). Although the exact function of vitamin A on brain development and CSF regulation is not fully understood, it is clear that Vitamin A has an important role in brain development and its normal functioning (27).
[[File:Rabbithhdrocephalus.jpg|center|300 px|thumb|Young rabbit with hydrocephalus caused by Vitamin A deficiency. Note the abnormally shaped cranium inflamed in appearance.]]

[[File:SpinabifidaMeningocele1.jpg|right|300 px|thumb|Spina Bifida Meningocele has characteristic damage to the meninges of the spinal cord which are pushed out through an opening in the vertebrae as a cyst filled with CSF.]]
[[File:SpinaBifidaMyelomeningocele.jpg|right|300 px|thumb|Spina Bifida Myelomeningocele is the most severe form of spinabifida where the damaged spinal cord protrudes out with damaged meninges as a cyst filled with CSF.]]
[[File:SpinaBifidaOcculta1.jpg|right|300 px|thumb|Spina Bifida Occulta is the least severe as the spinal cord and meninges are undamaged.]]

'''Spina Bifida'''

In Australia, the risk of spina bifida is 1 in every 500 pregnancies. Spina bifida is a type of neural tube defect where vertebrae (which normally cover and protect the spinal cord) are not completely formed but are divided resulting in the defective spinal cord and its coverings to protrude through the opening (28,29).

There are three main types of Spina Bifida differentiated by their characteristic features:

1)Spina Bifida Meningocele characterized by normal spinal cord, divided outer vertebrae and meninges surrounding the spinal cord protruding from the divided vertebrae as a cyst (1,28).

2)Spina Bifida Myelomeningocele characterized by split outer vertebrae with spinal cord and its meninges protruding from the divided vertebrae as a cyst. Commonly found at lumbar vertebral level (1,28,29).

3)Spina Bifida Occulta characterized unfused vertebral arches and exposed vertebral canal. Spinal cord and its meninges still located in vertebral canal (1,28).

All forms of spina bifida are potentially fatal and in those where the spinal cord is damaged severe consequence arise including and paralysis and loss of sensation at and below the level of damage spinal cord damage (29,33). There is a lot of Spina bifida research using rabbit models to test the effective methods of correcting spina bifida. The occurrence of natural spina bifida in rabbits is rare and for experimental purposes it can be surgically created in rabbit fetuses during gestation (31,32). The process involves aesthetical sedation of the maternal rabbit at day 22 of gestation; a midline laparotomy performed and the desired type of spina bifida lesion created on the exposed fetus using forceps. Different methods for correcting spina bifida can then be tested and its effectiveness analysed (30,33,34).
[[File:Rabbitspinabifida1.jpg|center|350 px|thumb|Rabbit newborn with Spina Bifida. Note the unfused, divided vertebrae and exposed spinal cord.]]

'''Brachydactylia & Acheiropodia'''

[[File:Malformation1.jpg|right|150 px|thumb|Acheiropodia in rabbit characterized by amputations of the limbs and extremities.]]

[[File:Rabbitmalformation3.jpg|left|150 px|thumb|X-Ray study of rabbit limbs with malformed phalanges due to Brachydactylia.]]

Brachydactylia and Acheiropodia are genetic disorders characterized by skeletal malformation of the hands and feet (36,36). In Brachydactylia, the malformations commonly involve abnormal shortening of fingers and toes due to poorly formed or absent bones (35). Acheiropodia is characterized by more severe skeletal malformations including bilateral amputations of the distal upper and lower extremities as well as aplasia of the hands and feet. Although it is not fatal, the individual endures a very difficult life without hands and feet (37).

The inheritance mechanism of this diseases can has been studied through experiment using rabbits. Rabbits with abnormal genes coding for Brachydactylia and Acheiropodia are selected and bred to produce offspring with the disease (36). Brachydactylia and Acheiropodia are autosomal recessive disorders which means that two copies of an abnormal gene must be present in the affected individual in order for the disease to develop. Thus, each parent passes an abnormal gene to the offspring (35,36). The process of the malformation progresses from genotype to phenotype; small deletions on the chromosomes produce abnormal genes, the abnormal genes are then passed down to the offspring, the offspring that inherits two of the abnormal genes is unable to code for the correct proteins and as a result, there is failure in normal development of limb extremities in the embryo phenotype (37,38).

==Current Embryology Research==

There is currently great excitement in research involving rabbits in the fields of transgenesis, cloning and stem cells. We shall explore research in these areas by discovering some of the techniques used and how they have been applied to the rabbit model.

[[File:Trans1.jpg|right|170 px]]
[[File:Trans2.jpg|right|170 px]]
[[File:Trans3.jpg|right|170 px]]
[[File:Trans4.jpg|right|170 px]]
[[File:Trans5.jpg|right|170 px]]

'''Transgenic rabbit'''

A transgenic organism is one whose genome also contains genes from another species (39). The aim of creating a transgenic organism is to obtain a favorable characteristic in the organism’s phenotype (41). This desired characteristic of phenotype is obtained by altering the organism’s normal genotype to include the gene from another species with the desired characteristic (39,40).

The production of a transgenic organism involves several steps summarized below:

1) The chromosome and the desired gene on it are identified in an organism (39).

2) The gene is isolated from its DNA strand. This involves “cutting” it out of its DNA strand using enzymes called restriction endonucleases. The restriction endonucleases cut DNA at specific site so the desired gene can be removed from the DNA strand. The cut ends are known as “sticky ends” (39,40).

3) Separate DNA sequences for regulation sometimes have to be added to ensure the gene will work (40).

4) The gene is then inserted with a promoter sequence into the fertilized egg cell of a new organism producing recombinant DNA (39,44). To do this, firstly the new organism’s cell DNA must first be cut and the desired gene incorporated into it. The same enzymes are used to cut the new organism’s cell DNA because the DNA stands from the two different organisms will form matching sticky ends that will be attracted to and connect with each other in a process is called “annealing” (39,40,44).

5) DNA ligases are sealing enzymes found in all living organisms that help make and repair DNA (39,40). The DNA ligases are added to the annealed DNA fragments to help strengthen the bonds of the new recombinant DNA. The recombinant DNA is now transferred into the new organism’s fertilized egg by microinjection (44).

6) As the embryo develops and the recombinant genetic code read, new proteins are synthesized which code for the new desired phenotype characteristic in the transgenic organism (39,40).

Transgenic rabbits can be created in the laboratory by gene microinjection into the fertilized rabbit oocyte (44). In April 2000, a transgenic rabbit named Alba was born containing a gene from a Pacific Northwest jellyfish. The gene which was injected into a fertilized albino rabbit oocyte allows the rabbit to synthesize the green fluorescent protein (GFP) that is characteristic of the Pacific Northwest jellyfish. When illuminated correctly, Alba glows a bright green (43,46).

Transgenic rabbits have important research purposes. Transgenic rabbits can be created to model retinal degeneration (44). Retinal degeneration is a common problem with aging and diseases such as diabetes, and frequently leads to complete blindness (42). A genetic retinal degeneration disease called retinitis pigmentosa (RP) is created in these rabbits by introducing the “Pro347Leu” mutation of the rhodopsin gene into fertilized rabbit eggs (43,44). As the rabbit grows, it develops the disease which becomes progressively worse (45).
The use of these transgenic rabbits ultimately leads to better understanding of the disease and more effective treatments (42). [[File:Transgenic rabbit.jpg|center|250 px|thumb|"Alba" A trangenic rabbit with a gene from a Pacific Northwest jellyfish that allows it to synthesize the green fluorescent protein (GFP) of the jellyfish.]]

[[File:Crabbit 1.jpg|right|170 px]]
[[File:Rabbit2.jpg|right|170 px]]
[[File:Rabbit3.jpg|right|170 px]]
[[File:Crabbit 4.jpg|right|170 px]]

'''Cloning'''

Cloning is a method of producing genetically identical organisms. The principle of cloning relies on “tricking” an egg cell to begin rapidly dividing into an embryo (39). In the normal fertilization process, two haploid sex cells unite to form a diploid zygote which begins rapidly dividing into an embryo (40). By replacing the haploid egg cell nucleus with a diploid somatic cell nucleus, the egg cell is tricked into thinking it is fertilized and hence begins rapidly dividing to form an embryo (39,40,41).

The process of cloning involves several steps summarized as the following using a rabbit example:

1) A somatic cell is obtained from a rabbit and the nucleus removed (39).

2) An egg cell is obtained from a donor rabbit and the nucleus of the egg cell removed using an enucleation needle. The cell is now called an enucleated egg cell (egg cell without a nucleus) (39,41).

3) The nucleus of the somatic cell is inserted into the enucleated egg cell (41).

4) The cell is now stimulated to divide by applying pulses of electric current (39).

5) The rapidly dividing cell develops in culture for a few days forming the early embryo (40,41).

6) The embryo is then implanted into the uterus of another rabbit similar to the egg cell donor. This rabbit is called the surrogate mother (40,41).

7) The embryo develops and the surrogate mother gives birth to a rabbit fetus with near identical genotype of the somatic cell donor (the small genomic difference is caused by the fetus obtaining mitochondrial DNA from the egg cell donor) (39,41).

The cloning of rabbits has been achieved by inserting the diploid nucleus of a rabbit fibroblast (the principal cells in connective tissue) into an enucleated oocyte (49). There is currently much focus on the creation of controversial but revolutionary interspecies hybrid embryos where the nucleus from a human somatic cells are implanted into an enucleated egg cell of another animal (50). The resulting embryo (known as a chimera) will be almost completely human genotype but will have genome from the other animal (48). In 2003, scientists at the Shanghai Second Medical University fused human cell with rabbit eggs creating the first human-rabbit hybrid using the nucleus transfer technique. The hybrid embryo developed in culture for a few days before it was destroyed and the stem cells harvested (47,48). The purpose of the research into creating hybrid embryos is to provide researchers with human stem cells for experimentation into cures for diseases such as cystic fibrosis, Alzheimer’s and Motor Neuron disease as human stem cell are difficult to obtain (50).

[[File:Rabbit clone.jpg|center|450 px|thumb|(A) Cloned rabbits (5 month old) from nuclear transfer technique. (B) The male rabbit whose fibroblasts were used as the nuclear donors. The cloned rabbits have almost identical genome to the male donor.]]

'''Stem Cells'''
[[File:HES.jpg|right|200 px|thumb|Human Embryonic Stem cell (hES).]]
[[File:Rabbit knee.jpg|right|200 px|thumb|Stem cell induced cartilage repair of knee in rabbit.]]

Stem cells are unspecialized cells which are able to continuously reproduce themselves and under appropriate conditions, differentiate into all the various specialized cells of the organism such as cardiac cells, neurons and blood cells (39,40). Adults have a small number of stem cells when compared to a developing embryo and the stem cell of an embryo more easily obtained (41). Human embryonic stem cells (hES) derived from the inner mass of the preimplantation blastocyst have the potential to differentiate into all cell types in the human body and thus are valued by researchers (50). However, due to ethical and political issues, the obtaining and experimentation on human embryonic stem cells is difficult and alternate means are needed as stem cell provides potentially new treatments for a range of diseases (54).

Rabbits can be used both in the obtaining of stem cell for experimentation and also as recipients of stem cells to cure diseases. The human-rabbit hybrid embryo provides a method of obtaining stem cells for experimentation and these stem cells possess many similar properties to human stem cells, including expression of surface markers, special growth requirements, capabilities of self renewal, formation of embryonic body and differentiation into cells of all three germ layers (53).

Stem cell experimentation on rabbits also focuses on transplanting stem cell into rabbits to treat specific diseases. A study at Zhejiang University where a research team transplanted human mesenchymal stem cell into New Zealand white rabbits with myocardial infarction recoded regeneration of vascular structure and improvement in cardiac function. The research team noted the potential of stem cells in differentiating into specialized cardiac cells when subjected to the specific conditions of the rabbit heart (52).

Another study at Hallym University tested the effectiveness of transplanting mesenchymal stem cells from New Zealand white rabbits into damaged cartilage in the knees of other New Zealand white rabbits. In the experiment, mesenchymal stem cells were obtained from the rabbit bone marrow and injected into the knees of other rabbits that had cartilage in their knees surgically damaged. The research team were able to conclude notable cartilage recovery in the rabbits with the mesenchymal stem cell injection and the potential of mesenchymal stem cells to differentiate into fibroblasts, adipoblasts, osteoblasts and chondroblasts (51,53).

The findings in stem cell experimentation with in rabbits yielded positive results and potentially opens a new field of research in the use of stem cell to treat a range of diseases in humans.

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#Biggers J.D (1991) Walter Heape FRS: a pioneer in reproductive biology. centenary of his embryo transfer experments.''Journals of reproduction and fertility''. ''93''(1)
# Stoodley, M (2006). Hydrocephalus. Prince of Wales Clinical School. Retrieved from [http://www.brainaustralia.org.au/AZ_of_Brain_Disorders/hydrocephalus]
# National Institute of Neurological Disorders and Stroke (2008, February). Hydrocephalus Fact Sheet. Retrieved from [http://www.ninds.nih.gov/disorders/hydrocephalus/detail_hydrocephalus.htm]
# Lewin, R (1999). Is Your Brain Really Necessary?. 24) Developmental Medicine & Child Neurology, 41. Retrieved from [http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=176431]
# Bigio, M.R, & Bruni J.E (1991). Silicone oil-induced hydrocephalus in the rabbit . Child's Nervous System, 7(2), Retrieved from [http://www.springerlink.com/content/b011477724837152/]
# Geelen, J.A (1974). A case of hydrocephalus and meningoencephalocele in a rabbit, caused by aqueductal malformation. Laboratory Animals, 8(2), Retrieved from [http://la.rsmjournals.com/cgi/content/abstract/8/2/167]
# LAMMINGX, G.E (1954). 27) Hydrocephalus in Young Rabbits Associated with Maternal Vitamin A Deficiency. British Journal of Nutrition, 8(2), Retrieved from [http://journals.cambridge.org/download.php?file=%2FBJN%2FBJN8_04%2FS0007114554000554a.pdf&code=10bb1dbc4a9e57a091f4e05f6aebbcf2]
# Carney, A (2008, February ). Spina bifida. Retrieved from [http://www.spinabifida.asn.au/]
# Better Health Channel (2008, October ). Spina bifida explained . Retrieved from [http://www.betterhealth.vic.gov.au/bhcv2/bhcarticles.nsf/pages/Spina_bifida_explained]
# Peeters, M.C, Viebahn, C, & Hekking, J.W (1998). Neurulation in the rabbit embryo . Anatomy and Embryology, 197(3), Retrieved from [http://www.springerlink.com/content/1efyteewgetjlwyg/]
# George, T.M, & Fuh E (2003). Review of Animal Models of Surgically Induced Spinal Neural Tube Defects: Implications for fetal surgery. Pediatric Neurosurgery , 39(2), Retrieved from [http://content.karger.com/produktedb/produkte.asp?typ=fulltext&file=PNE2003039002081]
# Pedreira, D.A, & Valente P.R (2002). A Different Technique to Create a 'Myelomeningocele-Like' Defect in the Fetal Rabbit. Fetal diagnosis and therapy, 17(6), Retrieved from [http://content.karger.com/ProdukteDB/produkte.asp?Doi=65388]
# Patten, B.M (1953). Embryological stages in the establishing of myeloschisis with spina bifida. The American journal of anatomy, 93(3), Retrieved from [http://deepblue.lib.umich.edu/handle/2027.42/49611]
# Pedreira, D.A, & Valente P.R (2003). Successful Fetal Surgery for the Repair of a 'Myelomeningocele-Like' Defect Created in the Fetal Rabbit. Fetal Diagnosis and Therapy, 18. Retrieved from [http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowPDF&ProduktNr=224239&Ausgabe=229041&ArtikelNr=69378]
# Lecklitner, M.L, & Douglas K.P (1986). Osteoscintigraphy and brachydactylia of the hand . European Journal of Nuclear Medicine and Molecular Imaging, 12(9), Retrieved from [http://www.springerlink.com/content/t82l77282x579102/]
# Greene, H.S, & Saxton J.A (1938). HEREDITARY BRACHYDACTYLIA AND ALLIED. ABNORMALITIES IN THE RABBIT. THE JOURNAL OF EXPERIMENTAL MEDICINE , 69. Retrieved from [http://jem.rupress.org/cgi/reprint/69/2/301.pdf]
# P. Ianakiev, M. van Baren, M. Daly, S. Toledo, M. Cavalcanti, J. Neto, E. Silveira, A. Freire-Maia, P. Heutink, M. Kilpatrick. Acheiropodia Is Caused by a Genomic Deletion in C7orf2, the Human Orthologue of the Lmbr1 Gene. The American Journal of Human Genetics, 68. Retrieved from [http://linkinghub.elsevier.com/retrieve/pii/S0002929707624707]
# Walbaum, R, Hazard, C, & Cordier, R (1976). Brachydactylia with symphalangism, probably autosomal recessive . Human Genetics, 33(2), Retrieved from [http://www.springerlink.com/content/m630p6880661486n]
# Campbell, N.A, & Reece, J.B (2002). Biology 6th Edition. USA: Benjamin Cummings.
# Solomon, E.P, Berg, L.R, & Martin, D.W (2002). Biology 6th Edition. USA: Thompson Learning.
# Glanville, A.R (2008). Scientifica. NSW, Australia: Millennium House.
# Lund, R.D (2008). Saving Vision with Skin Cells. Retrieved from [http://www.blindness.org]
# Jones, B.W, & Marc R.E (2008). Computational Molecular Phenotyping and Excitation Mapping in the P347L. Retinal Degeneration , (2986), Retrieved from [http://prometheus.med.utah.edu/]
# Kondo, M, Sakai, T, & Ueno, S (2009). Generation of a Transgenic Rabbit Model of Retinal Degeneration. Investigative Ophthalmology and Visual Science, 50. Retrieved from [http://www.iovs.org/cgi]
# Punzo, C, Chen, B, & Roesch, K (2009). PHOTORECEPTOR DEATH IN MOUSE MODELS OF RETINITIS PIGMENTOSA. Retrieved from [http://genepath.med.harvard.edu]
# Zimmer, M (2008). Alba. Retrieved from [http://www.conncoll.edu/ccacad/zimmer/GFP-ww/cooluses8.html]
# Scott, C (2006, May 1). Chimeras in the crosshairs. Nature Biotechnology , 24, Retrieved from [http://www.nature.com/nbt/journal/v24/n5/abs/nbt0506-487.html]
# Mott, M (2005, January 25). Animal-Human Hybrids Spark Controversy. National Geographic News, Retrieved from [http://theyfly.com/PDF/Nat.%20Geo.%20Animal-Human%20Hybrids.pdf]
# Li, S, & Chen X (2006). Rabbits generated from fibroblasts through nuclear transfer . Society for Reproduction and Fertility, 131. Retrieved from [http://www.reproduction-online.org/cgi/reprint/131/6/1085]
# Minger, S (2007). Interspecies SCNT derived human embryos. Regenerative Medicine, 2(2), Retrieved from [http://www.futuremedicine.com]
# Koga, H, Shimaya, M, & Muneta, T (2008). Local adherent technique for transplanting mesenchymal stem cells as a potential treatment of cartilage defect. Arthritis Research & Therapy, 10(4), Retrieved from [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2575632]
# Wang, J, Li, C, & Sun, Y (2005). Human bone marrow-derived mesenchymal stem cells transplanted into damaged rabbit heart to improve heart function. Journal of Zhejiang University Science, 6(4), Retrieved from [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1389731]
# Chen, Y, Liu, A, & Mao, W (2003). Embryonic stem cells generated by nuclear transfer of human somatic nuclei into rabbit oocytes. Cell Research , 13(4), Retrieved from [http://www.nature.com]
# Bethesda (2009, September 23). Stem Cell Information. Retrieved from [http://stemcells.nih.gov]
# Cibelli, J. B. (2002). Principles of cloning Amsterdam. Academic Press
# European rabbit (oryctolagus cuniculus) Retrieved 9/21/2009, 2009, from http://www.feral.org.au/content/species/rabbit.cfm
# Warner, S. (2003). Inositol transport in preimplantation rabbit embryos: Effects of embryo stage, sodium, osmolality and metabolic inhibitors Reproduction, 125(4), 479-493.
# Derelanko, M. J. (2008). The toxicologist's pocket handbook, second edition Informa HealthCare
# Beaudoin, S., Barbet, P., & Bargy, F. (2003). Developmental stages in the rabbit embryo: Guidelines to choose an appropriate experimental model Fetal Diagnosis and Therapy, 18(6), 422-427.

==Glossary==

Anesthetic - A drug that causes temporary loss of bodily sensations

Aplasia - The absence or defective development of a tissue or organ

Blastocyst - A stage of embryo development that occurs about five days after fertilisation when the embryo contains quite a few cells

Caudal - Situated towards the inferior or posterior end of the body

Cephalic - Relating to the head

Cerebral Aqueduct - A canal filled with cerebrospinal fluid within the midbrain

Cerebral Cortex - The layer of unmyelinated neurons (the grey matter) forming the cortex of the cerebrum of the brain

Cerebro Spinal Fluid (CSF) - A watery fluid which flows in the cavities within the brain and around the surface of the brain and spinal cord

Chromosome - Microscopic carriers of genetic material, composed of deoxyribonucleic acid (DNA) and proteins and appearing as rods under a microscope

Cisterna Magna - is one of three principal openings in the subarachnoid space between the arachnoid and pia mater layers of the meninges surrounding the brain

Diploid - A full set of genetic material, consisting of paired chromosomes one chromosome from each parental set

Dorsal - Position towards the back

Fontanel - Membranous gap between the bones of the cranium in an infant or fetus

Genome - All genetic information, the entire genetic complement and all of the hereditary material possessed by an organism. Made up of both chromosomal genome (inside the nucleus of the cell in the familiar form of chromosomes) and mitochondrial genome (outside the nucleus in the cytoplasm of the cell, usually in the form of one round chromosome (the mitochondrial chromosome))

Genotype - The genetic makeup of an organism

Glucocorticoids - A class of steroid hormones that bind to the glucocorticoid receptor (GR), which is present in almost every vertebrate

Haploid - A single set of chromosomes (half the full set of genetic material)

Laparotomy- Surgical incision into the abdominal wall; often done to examine abdominal organs

Ligases - Group of enzymes that catalyze the binding of two molecules

Oocyte - A female gametocyte that develops into an ovum after two meiotic divisions

Phenotype - The observable traits or characteristics of an organism, for example hair color, weight, or the presence or absence of a disease.

Pronuclear - Haploid nucleus before fusion of nuclei in fertilisation

Restriction Endonucleases - Enzymes that recognize and cleave specific DNA sequences, generating either blunt or single-stranded (sticky) ends

Retina - The thin layer of cells at the back of the eyeball where light is converted into neural signals sent to the brain

Rostral - Situated toward the oral and nasal region

Somite - Blocks of mesoderm on either side of the notochord and neural tube during development of the vertebrate embryo. Develop into muscles and vertebrae

Stenosis - Abnormal narrowing of a bodily canal or passageway

Weaning - Young become accustom to nourishment other than suckling

==Links to Research Laboratories and Researchers==

1) Transgenic lab: [http://www.dnavision.be/index.php]

Involved in development of transgenic organisms, DNA construction and phenotype analysis.

2) World Rabbit Science Association: (WRSA) [http://world-rabbit-science.com]

International Association where researchers exchange knowledge and encourage teaching, scientific research, practical experimentation, the collection and publication of statistics and documents relating to the rabbit. Even have their own journal called “World Rabbit Science”

Website provides contact with researchers, professors and veterinarians working with rabbits.

Example: Dr. Myriam Kaplan-Pasternak, Doctorate Veterinary Medicine, University of California, myriamsemail@gmail.com

3) American Veterinary Medical Association [http://www.avma.org]

The American Veterinary Medical Association (AVMA), established in 1863, is a not-for-profit association representing more than 78,000 veterinarians working in private and corporate practice, government, industry, academia, and uniformed services. Excellent website into animal research and has a range of veterinary journals.

{{Template:Projects09}}
[[Category:Rabbit]]
[[File:Example.jpg]]

2009 Group Project 1

2009-10-14T12:19:59Z

Z3185685: /* Abnormal Development */

[[File:Rabbits.png|right|400 px]]

== '''THE RABBIT (ORYCTOLAGUS CUNICULUS)''' ==

==Introduction==

[[File:Isidro_Martinez.jpg‎|left|175 px]]

Several characteristics of the rabbit make it an excellent model for study. This will be further explored in "The History of Model Use" section of this page. Many studies have resulted in the development and improvement of various micro-manipulation techniques such as the production of transgenic rabbits. Unlike many other species such as the chick or rat, relatively little is known about the development of a rabbit. Nevertheless, it is still an appropriate animal model as the results from many experiments are significant to that of other mammals, including humans. (55)

A rabbits potential for reproduction is high, breeding from the early stages of 3 to 4 months of age. A mature female rabbit can be pregnant from 6 to 8 months in a year, producing up to 30 to 40 young in this time. (56)

==History of Model Use==

'''WHY are we using rabbits?'''

ADVANTAGES
*Provides repeatability of animal model studies
*Large enough for single samples
*Many stocks/strains as animal models
*Easily managed
*Quality of immunologic products
*Ease of reproductive control

DISADVANTAGES
*Most colonies are a storehouse of diseases
*Extremely variable to responses to general anesthetics

'''Brief timeline of rabbit embryo model use'''

*1672- de Graaf found the Graffian follicle.
*1890- Walter Heape succeeded first mammalian embryo transfer
*1906- FT Lewis discovered the development of the lymphatic system in rabbit embryos.
*1941- Dr. Pincus succeeded in keeping rabbit embryos developing in the test
*1968- Edwards and Gardner successfully performed the first known embryo biopsy on rabbit embryos

=== Regnier de Graaf (1641–1673) ===
[[image:Ovary_Graaf.jpg|thumb|250px|left|drawing of ovary]]
[[File:Regnier de Graaf.jpg|right]]

'''Discovery of the Graafian Follicles'''

In 1672 de Graaf published ''The Generative Organs of Women'', which was primarily a study of development in the rabbit. When de Graaf discovered large, round welling on the ovaries of rabbits, he assumed they were mammalian eggs. De Graaf also described the corpus luteum.

He summarised the previous works from anatomists, but unable to experience the amazing benefits made by microscopy.
But Antonie van Leeuwenhoek (A microbiologist, 1632 - 1723) argued that the structures now known as Graafian follicles could not be eggs. Haller suggested that the egg might be formed by the coagulation of the fluid within the Graafian follicle. De Graaf noted that the “egg” did not contain a tiny embryo, but he thought it did contain the “germ” of the future organism. (3)

=== Walter Heape (1855-1928) ===
'''First case of embryo transfer experiments'''

On 27 April 1890, Walter Heape (a professor and physician at the University of Cambridge, England) transferred rabbit embryos from one mother to another. (7) One rabbit mother became pregnant and delivered young from the transferred embryos. This was the first mammalian embryo transfer experiment to be successfully completed. His embryo transfer work in perspective as it relates to other contributions of this pioneer in reproductive biology.(7)

In 1891, Walter Heape had been conducting research on reproduction in numerous animal species. Working with two species of rabbits, he flushed embryos from the rabbit fallopian tubes of one breed (Angora) and placed them into the uterus of a recently mated Belgian hare. In the resulting litter, there were 4 Belgians and 2 Angoras. Heape proved that it was possible to take preimplantation embryos and transfer them to a gestational carrier without affecting their development.(7)

===Dr. Gregory Goodwin Pincus (1903-1967) ===

'''Contraceptive pill'''

Dr. Pincus began studying hormonal biology and steroidal hormones early in his career. His first breakthrough came when he was able to produce in vitro fertilization in rabbits (by using chemicals) in 1934. Throughout their hormonal contraceptive research Pincus, along with reproductive physiologist Min Chueh Chang, found out progesterone would act as an inhibitor to ovulation. They co-invented the combined oral contraceptive pill.[2][6]

===Genetic Diagnosis===
In 1968, Robert Edwards and David Gardner reported the successful sexing of rabbit blastocysts, setting the first steps towards PGD (Preimplantation Genetic Diagnosis). It was not until the 1980s that human IVF was fully developed, which coincided with the breakthrough of the highly sensitive polymerase chain reaction (PCR) technology. Handyside and collaborators' first successful attempts at testing were in October 1989 with the first births in 1990 though the preliminary experiments had been published some years earlier. In these first cases, PCR was used for sex determination for patients carrying X-linked diseases.(12)

==Timeline of Embryo Development==

The following is a timeline, adapted from Cibelli (2002), of the main events of preimplantation development in rabbits. The time is measured in hours post-mating and shows the embryo stage (cell number) in each time scale.

[[File:Morula1.JPG|right|200 px|thumb|A day 2 early morula]]

'''12-14 hours:''' Oocyte; Fertilization

'''18-20 hours:''' Zygote; Pronuclear formation

'''24-26 hours:''' Two cell

'''30-32 hours:''' Four cell

'''38-40 hours:''' Eight cell; Maternal-zygotic transition

'''46-48 hours:''' Sixteen cell

'''54-56 hours:''' Morula (32 cell); Compaction and transport to uterus

'''64-66 hours:''' Compact morula (64 cell); Morula-blastocyst transition

'''76-78 hours:''' Early blastocyst (128 cell)

'''84-86 hours:''' Expanded blastocyst (256 cell); Blastocoels expansion

'''94-96 hours:''' Hatched blastocyst (512 cell); Hatching

The following shows a diagrammatic representation of the relative sizes of rabbit embryos. The sizes do not include the embryonic coverings such as the zona pellucida and mucin coat. This diagram has been adapted from Warner (2003).

[[File:Sizes.JPG]]

The following timelines show a comparison of the developmental stages between human and rabbit embryos. They have been adapted from Derelanko (2008). "The similarities of this developmental pattern in humans and rabbits, suggests that the same growth increment is required to achieve the same stage. The main difference observed between human rabbit gestational duration is due to the fetal growth phase. The reason for this may be due to birth weight, lifetime and the neural complexity of the species." (59)

[[File:Timeline_rabbit.JPG]]

The following timelines have been adapted from a study carried out by Beaudoin et al. on the development of rabbit embryos.

==='''Body Form'''===

'''8.5 days''': Embryo thickens. First somites appear. Rostral neuropore closes. Caudal neuropore remains open

'''9.5 days''': Dorsal curvature begins. Cardiac mass bulges under cephalic pole.

'''10.5 - 13.5 days''': Dorsal curvature increases. Body thickens. Softening of the cephalic domination straightens the embryo.

'''17.5 days''': Neck becomes visible.

==='''Limb Development'''===

''' 9.5 days''': Rostral limb bud appears

'''10.5 days''': Caudal limb bud appears

'''12.5 days''': Hand plate becomes present. Limbs become disposed.

'''13.5 days''': Foot plate and finger rays become visible.

'''14.5 days''': Rostral and caudal limbs become parallel.

'''15.5 days''': Elbow appears.

'''16.5 days''': Fingers start to elongate.

'''17.5 days''': Knee becomes visible

'''19.5 days''': Hands and feet merge on the midline. Three segments of limbs become distinguished.

==='''Abdominal Wall Development'''===

'''9.5 days''': Abdominal wall is limited to the embryonic pedicle under the cardiac mass.

'''13.5 days''': First intestinal loops appear in the umbilical cord.

'''14.5 days – 17.5''': Rapid intestinal development in the cord.

'''15.5 days''': Abdominal vesicles can be observed.

'''16.5 days''': Cecal bud becomes present outside the abdomen

'''18.5 days''': Bowel returns to the abdominal cavity and umbilical ring closes.

==='''Cephalic Development'''===

'''9.5 days''': One cerebral vesicle can be seen. Pharyngeal arches as optic vesicle are present.

'''10.5 days''': Three arches are distinguished in the cephalic pole.

'''11.5 days''': Three cerebral vesicles present. Optic plate is distinguished.

'''12.5 days''': Face develops nasal, maxillar and mandibular buds. Lens vesicle is closed. Five cerebral vesicles exist.

'''14.5 days''': The ear becomes refined. Face can be distinguished from the brow.

'''18.5 days''': Eyelid appears, covering the eyes.

==Staging==

The following stages have been adapted from Beaudoin et al. (2003). Table 1 represents at each age its corresponding stage defined by the Carnegie classification

{| class="wikitable" style="text-align:center; width: 800px; height:1000px" border="1"
|+'''Table 1. Rabbit developmental stages using Carnegie classification'''

|- style="height:50px"
! '''Stage''' !! '''Days''' !! '''Event''' !! '''Image'''
|- style="width:200px"
! width="50" | 10
| width="50" | 8.5 || First somites appear, rostral neuropore closes
|- style="height:75px"
! 12
| 9.5 || Rostral limb bud, embryonic pedicle, caudal neuropore closes, one cerebral vesicle, pharyngeal arches, completion of optic vesicle
| [[file: 9.5new.JPG|100px]]
|- style="height:75px"
! 13
| 10.5 || Dosral C-shaped curvature, caudal limb bud, prominent cardiac swelling, four pharyngeal arches
| [[file: 10.5new.JPG|100px]]
|- style="height:75px"
! 14
| 11.5 || Three cerebral vesicles, optic plate, mesonephric ridge
|- style="height:75px"
! 15
| 12.5 || Hand plate, wheel ray limbs, lens vesicle closes, five cerebral vesicles, facial buds, vertebrae
| [[file: 12.5new.JPG|100px]]
|- style="height:75px"
! 16
| 13.5 || Foot plate, finger rays, prominent liver, intestinal loops, auricular hillocks
| [[file: 13.5new.JPG|100px]]
|- style="height:100px"
! 19
| 14.5 || Cuboidal body, trunk straightens, parallel limbs, toe rays, modeled face, visible auricle
| [[file: 14.5new.JPG|100px]]
|- style="height:75px"
! 20
| 15.5 || Elbow, fingers elongate, notches between toe rays
| [[file: 15.5new.JPG|100px]]
|- style="height:75px"
! 21-22
| 16.5 || Toes free, cecal bud in intestinal hernia
| [[file: 16.5new.JPG|100px]]
|- style="height:75px"
! 22-23
| 17.5 || Knee, neck, eyelids
| [[file: 17.5new.JPG|100px]]
|- style="height:75px"
! 23
| 18.5 || Hands and feet join at the midline, closure of abdominal wall, eyelids cover eyes
| [[file: 18.5new.JPG|100px]]
|-
| colspan="4" align="center"| Following this stage fetal appearance is completed, organogenesis is achieved
|}

==Genetics==

===Sequencing===
The National Human Genome Research Institute selected the European rabbit (Oryctolagus cuniculus) for whole genome sequencing to enhance their understanding of the human genome and use it experimentally for an animal model for human disease. (8)

The rabbit has been sequenced twice by The Broad Institute as part of the mammalian genome project. It is now currently undergoing 7 more sequencing projects. Its sequencing is made by the Whole Genome Shotgun (WGS) and assembly method. (9) This is when genomic DNA is sheared into small pieces of approximately 2000 base pairs which are then cloned into plasmids and sequenced on both strands. Once the contig fragments are read, realigned and reassembled by computer algorithms, it will give the overall sequence. (10) (11) The image below shows diagramatically how the two types of sequencing are different. The same techniques are used for sequencing the human genome (in 2003). [A contig is a set of overlapping DNA segments, derived from a single source of genetic material, from which the complete sequence may be deduced.

The whole genome shotgun (WGS) has serious gaps, yet the information has already proven useful for immunological as well as in silico studies. Deeper 7x coverage started in September 2007. The NCBI Rabbit Genome Resources site has links to searches for genes in the assemblies of the 2x WGS sequence at Ensembl and UCSC.(12) [http://www.broadinstitute.org/models/europeanrabbit/ Rabbit Genome Project]

[[File:WGS_sequencing.gif‎|center|800 px]]

===Genome===
The Rabbit genome was published by two groups (9)
# Lindblad-Toh,K., Chang,J.L., Gnerre,S., Clamp,M. and Lander,E.S. published their admission of 84024 bases on May 5th 2005 to The Broad Institute (USA) by shotgun sequencing
# Di Palma,F., Heiman,D., Young,S., Gnerre,S., Johnson,J., Lander,E.S. and Lindblad-Toh,K. published their admission of 84024 bases on August 3rd 2009 to The Broad Institute (USA) by shotgun sequencing.
The rabbit's genome is sequenced and on display in the Nucleotide Data Bank. It is too long to produce here. A link to the data bank is provided: [http://www.ncbi.nlm.nih.gov/nuccore/256946799/ Rabbit Genome from the Nucleotide Data Bank]

[[File:8cellembryo.jpg|thumb|Individual mitochondria (arrowheads) of an 8cell Rabbit embryo]]

The rabbit genome was sequenced in 2005 by Ensembl and managed to produce: (13)
* 2,076,044,328 supercontigs (ordered Contigs with gaps)
* 495 Known protein-coding genes
* 11,357 Projected protein-coding genes
* 2,343 RNA genes
* 212,581 Gene exons
* 20,311 Gene transcripts

For further research the taxonomy ID number for the Rabbit is: 9986 [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=9986&lvl=3&lin=f&keep=1&srchmode=1&unlock/ Taxonomy Data]

===Mitochondrial Genome===
The mitochondiral genome (mtDNA) of the rabbit was sequenced on November 14th 2006 with 17245 base pairs/nucleotides in circular form. Apparently the "length is not absolute due to the presence of different numbers of repeated motifs in the control region".
PMID 9653643

The image to the right shows the mitochondria during cell division and multiplication in embryo development.

=== Chromosomes ===
Over the years there have been various data suggesting the diploid chromosomal number for the rabbit may range from 22-42. However through recent research and an abundance of trials suggest that the rabbit does indeed have 22 different chromosome pairs existing in each cell of the rabbit. (16)(17) The sex chromosomes of the rabbit are of X-Y type convincingly (17). In a study in Bombay it confirmed that a rabbit has 2n = 44 chromosomes. There were 21 pairs of autosomes, out of which 1 to 6 were metacentric, 7 to 11 submetacentric, 12 to 17 subtelocentric and 18 to 21 acrocentric, plus the sex chromosomes. The image to the left shows a female rabbit with no chromosomal abnormalities. (19)

'''Comparison to human chromosome:'''

Rabbit chromosomes 12, 19 and X were found to be completely homologous to human chromosomes 6, 17 and X, respectively. All other human chromosomes were homologous to two or sometimes three rabbit chromosomes. (14) Chromosome 12 was shorter than chromosomes 13 and 14. (15) The image below illustrates the human chromosome (2n = 46).

[[File:Drawn chromosome.jpg|left|400 px]]

[[File:Karyotypehuman.gif|right|500 px]]

'''Abnormalities'''

These are generally more apparent during early embryo development in blastocysts from delayed fertilization. Some examples of abnormal development include cases of: (18)
* hypoploidy; 1 chromosome missing from a pair (2n = 43),
* double hypoploidy; 2 chromosomes missing from 2 different pairs (2n = 42),
* mosaicism (different chromosomal makeup in some cells).

Another study also found these abnormalities as well as: (19)
* autosomal trisomy (3 autosomes per pair),
* triploidy (extra set of chromsomes),
* mixoploidy (unequal number of chromosome sets in adjacent cells), and
* short arm deletion (deletion of parts of chromosomes).

A specific abnormality occurring in rabbits is the x-linked tremor. There is a mutation in exon 2 of the prteolipid-protein (PLP 1) gene, corresponding to the end of the first potential transmembrane domain of the protein. This disorder affects myelination of the central nervous system. OMIA ID:12 [http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=full_report&list_uids=100009169&log$=omiamaingene| Gene:100009169]

==Abnormal Development==

Abnormal embryological development is a vast field of study that has been the subject of recent research papers. Our investigation of abnormal development in rabbit embryology will focus on abnormalities commonly found in both rabbit and human embryos. We will explore the nature of these abnormalities in both humans and rabbits.

[[File:Normal v Abnormal.jpg|right|300 px|thumb|Brain MRI of patient with Hydrocephalus (left) compared to a normal brain (right). An obvious increase in ventricular size and a significant decrease in brain size is present.]]
[[File:Ventricle_Expansion.jpg|right|300 px|thumb|CSF accumulation in ventricles of brain increasing intracranial pressure.The pressure from the expanding ventricles force the brain and skull to grow outwards abnormally.]]

'''Hydrocephalus'''

Annually, one in every 1000 children born in Australia have hydrocephalus. Hydrocephalus occurs when excessive cerebrospinal fluid (CSF) accumulates in the brain and can result in severe disability and even death because the disorder can result in complete or near complete destruction of the cerebral cortex (22).

Children born with hydrocephalus typically exhibit abnormally large head circumference and bulging cranial fontanels as a result of increased intracranial pressure on the brain from the accumulating CSF (22,23). As CSF accumulates in the ventricles and CSF compartments of the brain, it expands forcing the brain to grow outward. The outward growing brain places pressure on the skull which in turn also grows outwards giving rise to an abnormally large head circumference and bulging cranial fontanels (22,24). It is generally acknowledged that children with hydrocephalus have mental retardation, often to the degree of being “vegetative” (24).

The serious consequences of this disease mean that much research is necessary to unearth methods of prevention and effective treatment. One of the modes of studying hydrocephalus is to use the rabbit experimental model where hydrocephalus can be induced in rabbit embryo’s. The injection of silicone oil into the cisterna magna of the brain is one way of inducing hydrocephalus in the rabbit embryo. The silicone oil obstructs the normal flow of CSF resulting in CSF accumulation in the brain leading to hydrocephalus (25). Another method of inducing hydrocephalus in rabbit embryo’s is by intentional vitamin A deprivation of pregnant dams. The vitamin A deficiency results in raised intracranial CSF pressure and aqueduct stenosis causing poor circulation of CSF leading to hydrocephalus (26,27). Although the exact function of vitamin A on brain development and CSF regulation is not fully understood, it is clear that Vitamin A has an important role in brain development and its normal functioning (27).
[[File:Rabbithhdrocephalus.jpg|center|300 px|thumb|Young rabbit with hydrocephalus caused by Vitamin A deficiency. Note the abnormally shaped cranium inflamed in appearance.]]

[[File:SpinabifidaMeningocele1.jpg|right|300 px|thumb|Spina Bifida Meningocele has characteristic damage to the meninges of the spinal cord which are pushed out through an opening in the vertebrae as a cyst filled with CSF.]]
[[File:SpinaBifidaMyelomeningocele.jpg|right|300 px|thumb|Spina Bifida Myelomeningocele is the most severe form of spinabifida where the damaged spinal cord protrudes out with damaged meninges as a cyst filled with CSF.]]
[[File:SpinaBifidaOcculta1.jpg|right|300 px|thumb|Spina Bifida Occulta is the least severe as the spinal cord and meninges are undamaged.]]

'''Spina Bifida'''

In Australia, the risk of spina bifida is 1 in every 500 pregnancies. Spina bifida is a type of neural tube defect where vertebrae (which normally cover and protect the spinal cord) are not completely formed but are divided resulting in the defective spinal cord and its coverings to protrude through the opening (28,29).

There are three main types of Spina Bifida differentiated by their characteristic features:

1)Spina Bifida Meningocele characterized by normal spinal cord, divided outer vertebrae and meninges surrounding the spinal cord protruding from the divided vertebrae as a cyst (1,28).

2)Spina Bifida Myelomeningocele characterized by split outer vertebrae with spinal cord and its meninges protruding from the divided vertebrae as a cyst. Commonly found at lumbar vertebral level (1,28,29).

3)Spina Bifida Occulta characterized unfused vertebral arches and exposed vertebral canal. Spinal cord and its meninges still located in vertebral canal (1,28).

All forms of spina bifida are potentially fatal and in those where the spinal cord is damaged severe consequence arise including and paralysis and loss of sensation at and below the level of damage spinal cord damage (29,33). There is a lot of Spina bifida research using rabbit models to test the effective methods of correcting spina bifida. The occurrence of natural spina bifida in rabbits is rare and for experimental purposes it can be surgically created in rabbit fetuses during gestation (31,32). The process involves aesthetical sedation of the maternal rabbit at day 22 of gestation; a midline laparotomy performed and the desired type of spina bifida lesion created on the exposed fetus using forceps. Different methods for correcting spina bifida can then be tested and its effectiveness analysed (30,33,34).
[[File:Rabbitspinabifida1.jpg|center|350 px|thumb|Rabbit newborn with Spina Bifida. Note the unfused, divided vertebrae and exposed spinal cord.]]

'''Brachydactylia & Acheiropodia'''

[[File:Malformation1.jpg|right|150 px|thumb|Acheiropodia in rabbit characterized by amputations of the limbs and extremities.]]

[[File:Rabbitmalformation3.jpg|left|150 px|thumb|X-Ray study of rabbit limbs with malformed phalanges due to Brachydactylia.]]

Brachydactylia and Acheiropodia are genetic disorders characterized by skeletal malformation of the hands and feet (36,36). In Brachydactylia, the malformations commonly involve abnormal shortening of fingers and toes due to poorly formed or absent bones (35). Acheiropodia is characterized by more severe skeletal malformations including bilateral amputations of the distal upper and lower extremities as well as aplasia of the hands and feet. Although it is not fatal, the individual endures a very difficult life without hands and feet (37).

The inheritance mechanism of this diseases can has been studied through experiment using rabbits. Rabbits with abnormal genes coding for Brachydactylia and Acheiropodia are selected and bred to produce offspring with the disease (36). Brachydactylia and Acheiropodia are autosomal recessive disorders which means that two copies of an abnormal gene must be present in the affected individual in order for the disease to develop. Thus, each parent passes an abnormal gene to the offspring (35,36). The process of the malformation progresses from genotype to phenotype; small deletions on the chromosomes produce abnormal genes, the abnormal genes are then passed down to the offspring, the offspring that inherits two of the abnormal genes is unable to code for the correct proteins and as a result, there is failure in normal development of limb extremities in the embryo phenotype (37,38).

==Current Embryology Research==

There is currently great excitement in research involving rabbits in the fields of transgenesis, cloning and stem cells. We shall explore research in these areas by discovering some of the techniques used and how they have been applied to the rabbit model.

[[File:Trans1.jpg|right|170 px]]
[[File:Trans2.jpg|right|170 px]]
[[File:Trans3.jpg|right|170 px]]
[[File:Trans4.jpg|right|170 px]]
[[File:Trans5.jpg|right|170 px]]

'''Transgenic rabbit'''

A transgenic organism is one whose genome also contains genes from another species (39). The aim of creating a transgenic organism is to obtain a favorable characteristic in the organism’s phenotype (41). This desired characteristic of phenotype is obtained by altering the organism’s normal genotype to include the gene from another species with the desired characteristic (39,40).

The production of a transgenic organism involves several steps summarized below:

1) The chromosome and the desired gene on it are identified in an organism (39).

2) The gene is isolated from its DNA strand. This involves “cutting” it out of its DNA strand using enzymes called restriction endonucleases. The restriction endonucleases cut DNA at specific site so the desired gene can be removed from the DNA strand. The cut ends are known as “sticky ends” (39,40).

3) Separate DNA sequences for regulation sometimes have to be added to ensure the gene will work (40).

4) The gene is then inserted with a promoter sequence into the fertilized egg cell of a new organism producing recombinant DNA (39,44). To do this, firstly the new organism’s cell DNA must first be cut and the desired gene incorporated into it. The same enzymes are used to cut the new organism’s cell DNA because the DNA stands from the two different organisms will form matching sticky ends that will be attracted to and connect with each other in a process is called “annealing” (39,40,44).

5) DNA ligases are sealing enzymes found in all living organisms that help make and repair DNA (39,40). The DNA ligases are added to the annealed DNA fragments to help strengthen the bonds of the new recombinant DNA. The recombinant DNA is now transferred into the new organism’s fertilized egg by microinjection (44).

6) As the embryo develops and the recombinant genetic code read, new proteins are synthesized which code for the new desired phenotype characteristic in the transgenic organism (39,40).

Transgenic rabbits can be created in the laboratory by gene microinjection into the fertilized rabbit oocyte (44). In April 2000, a transgenic rabbit named Alba was born containing a gene from a Pacific Northwest jellyfish. The gene which was injected into a fertilized albino rabbit oocyte allows the rabbit to synthesize the green fluorescent protein (GFP) that is characteristic of the Pacific Northwest jellyfish. When illuminated correctly, Alba glows a bright green (43,46).

Transgenic rabbits have important research purposes. Transgenic rabbits can be created to model retinal degeneration (44). Retinal degeneration is a common problem with aging and diseases such as diabetes, and frequently leads to complete blindness (42). A genetic retinal degeneration disease called retinitis pigmentosa (RP) is created in these rabbits by introducing the “Pro347Leu” mutation of the rhodopsin gene into fertilized rabbit eggs (43,44). As the rabbit grows, it develops the disease which becomes progressively worse (45).
The use of these transgenic rabbits ultimately leads to better understanding of the disease and more effective treatments (42). [[File:Transgenic rabbit.jpg|center|250 px|thumb|"Alba" A trangenic rabbit with a gene from a Pacific Northwest jellyfish that allows it to synthesize the green fluorescent protein (GFP) of the jellyfish.]]

[[File:Crabbit 1.jpg|right|170 px]]
[[File:Rabbit2.jpg|right|170 px]]
[[File:Rabbit3.jpg|right|170 px]]
[[File:Crabbit 4.jpg|right|170 px]]

'''Cloning'''

Cloning is a method of producing genetically identical organisms. The principle of cloning relies on “tricking” an egg cell to begin rapidly dividing into an embryo (39). In the normal fertilization process, two haploid sex cells unite to form a diploid zygote which begins rapidly dividing into an embryo (40). By replacing the haploid egg cell nucleus with a diploid somatic cell nucleus, the egg cell is tricked into thinking it is fertilized and hence begins rapidly dividing to form an embryo (39,40,41).

The process of cloning involves several steps summarized as the following using a rabbit example:

1) A somatic cell is obtained from a rabbit and the nucleus removed (39).

2) An egg cell is obtained from a donor rabbit and the nucleus of the egg cell removed using an enucleation needle. The cell is now called an enucleated egg cell (egg cell without a nucleus) (39,41).

3) The nucleus of the somatic cell is inserted into the enucleated egg cell (41).

4) The cell is now stimulated to divide by applying pulses of electric current (39).

5) The rapidly dividing cell develops in culture for a few days forming the early embryo (40,41).

6) The embryo is then implanted into the uterus of another rabbit similar to the egg cell donor. This rabbit is called the surrogate mother (40,41).

7) The embryo develops and the surrogate mother gives birth to a rabbit fetus with near identical genotype of the somatic cell donor (the small genomic difference is caused by the fetus obtaining mitochondrial DNA from the egg cell donor) (39,41).

The cloning of rabbits has been achieved by inserting the diploid nucleus of a rabbit fibroblast (the principal cells in connective tissue) into an enucleated oocyte (49). There is currently much focus on the creation of controversial but revolutionary interspecies hybrid embryos where the nucleus from a human somatic cells are implanted into an enucleated egg cell of another animal (50). The resulting embryo (known as a chimera) will be almost completely human genotype but will have genome from the other animal (48). In 2003, scientists at the Shanghai Second Medical University fused human cell with rabbit eggs creating the first human-rabbit hybrid using the nucleus transfer technique. The hybrid embryo developed in culture for a few days before it was destroyed and the stem cells harvested (47,48). The purpose of the research into creating hybrid embryos is to provide researchers with human stem cells for experimentation into cures for diseases such as cystic fibrosis, Alzheimer’s and Motor Neuron disease as human stem cell are difficult to obtain (50).

[[File:Rabbit clone.jpg|center|450 px|thumb|(A) Cloned rabbits (5 month old) from nuclear transfer technique. (B) The male rabbit whose fibroblasts were used as the nuclear donors. The cloned rabbits have almost identical genome to the male donor.]]

'''Stem Cells'''
[[File:HES.jpg|right|200 px|thumb|Human Embryonic Stem cell (hES).]]
[[File:Rabbit knee.jpg|right|200 px|thumb|Stem cell induced cartilage repair of knee in rabbit.]]

Stem cells are unspecialized cells which are able to continuously reproduce themselves and under appropriate conditions, differentiate into all the various specialized cells of the organism such as cardiac cells, neurons and blood cells (39,40). Adults have a small number of stem cells when compared to a developing embryo and the stem cell of an embryo more easily obtained (41). Human embryonic stem cells (hES) derived from the inner mass of the preimplantation blastocyst have the potential to differentiate into all cell types in the human body and thus are valued by researchers (50). However, due to ethical and political issues, the obtaining and experimentation on human embryonic stem cells is difficult and alternate means are needed as stem cell provides potentially new treatments for a range of diseases (54).

Rabbits can be used both in the obtaining of stem cell for experimentation and also as recipients of stem cells to cure diseases. The human-rabbit hybrid embryo provides a method of obtaining stem cells for experimentation and these stem cells possess many similar properties to human stem cells, including expression of surface markers, special growth requirements, capabilities of self renewal, formation of embryonic body and differentiation into cells of all three germ layers (53).

Stem cell experimentation on rabbits also focuses on transplanting stem cell into rabbits to treat specific diseases. A study at Zhejiang University where a research team transplanted human mesenchymal stem cell into New Zealand white rabbits with myocardial infarction recoded regeneration of vascular structure and improvement in cardiac function. The research team noted the potential of stem cells in differentiating into specialized cardiac cells when subjected to the specific conditions of the rabbit heart (52).

Another study at Hallym University tested the effectiveness of transplanting mesenchymal stem cells from New Zealand white rabbits into damaged cartilage in the knees of other New Zealand white rabbits. In the experiment, mesenchymal stem cells were obtained from the rabbit bone marrow and injected into the knees of other rabbits that had cartilage in their knees surgically damaged. The research team were able to conclude notable cartilage recovery in the rabbits with the mesenchymal stem cell injection and the potential of mesenchymal stem cells to differentiate into fibroblasts, adipoblasts, osteoblasts and chondroblasts (51,53).

The findings in stem cell experimentation with in rabbits yielded positive results and potentially opens a new field of research in the use of stem cell to treat a range of diseases in humans.

==References==

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==Glossary==

Anesthetic - A drug that causes temporary loss of bodily sensations

Aplasia - The absence or defective development of a tissue or organ

Blastocyst - A stage of embryo development that occurs about five days after fertilisation when the embryo contains quite a few cells

Caudal - Situated towards the inferior or posterior end of the body

Cephalic - Relating to the head

Cerebral Aqueduct - A canal filled with cerebrospinal fluid within the midbrain

Cerebral Cortex - The layer of unmyelinated neurons (the grey matter) forming the cortex of the cerebrum of the brain

Cerebro Spinal Fluid (CSF) - A watery fluid which flows in the cavities within the brain and around the surface of the brain and spinal cord

Chromosome - Microscopic carriers of genetic material, composed of deoxyribonucleic acid (DNA) and proteins and appearing as rods under a microscope

Cisterna Magna - is one of three principal openings in the subarachnoid space between the arachnoid and pia mater layers of the meninges surrounding the brain

Diploid - A full set of genetic material, consisting of paired chromosomes one chromosome from each parental set

Dorsal - Position towards the back

Fontanel - Membranous gap between the bones of the cranium in an infant or fetus

Genome - All genetic information, the entire genetic complement and all of the hereditary material possessed by an organism. Made up of both chromosomal genome (inside the nucleus of the cell in the familiar form of chromosomes) and mitochondrial genome (outside the nucleus in the cytoplasm of the cell, usually in the form of one round chromosome (the mitochondrial chromosome))

Genotype - The genetic makeup of an organism

Glucocorticoids - A class of steroid hormones that bind to the glucocorticoid receptor (GR), which is present in almost every vertebrate

Haploid - A single set of chromosomes (half the full set of genetic material)

Laparotomy- Surgical incision into the abdominal wall; often done to examine abdominal organs

Ligases - Group of enzymes that catalyze the binding of two molecules

Oocyte - A female gametocyte that develops into an ovum after two meiotic divisions

Phenotype - The observable traits or characteristics of an organism, for example hair color, weight, or the presence or absence of a disease.

Pronuclear - Haploid nucleus before fusion of nuclei in fertilisation

Restriction Endonucleases - Enzymes that recognize and cleave specific DNA sequences, generating either blunt or single-stranded (sticky) ends

Retina - The thin layer of cells at the back of the eyeball where light is converted into neural signals sent to the brain

Rostral - Situated toward the oral and nasal region

Somite - Blocks of mesoderm on either side of the notochord and neural tube during development of the vertebrate embryo. Develop into muscles and vertebrae

Stenosis - Abnormal narrowing of a bodily canal or passageway

Weaning - Young become accustom to nourishment other than suckling

==Links to Research Laboratories and Researchers==

1) Transgenic lab: [http://www.dnavision.be/index.php]

Involved in development of transgenic organisms, DNA construction and phenotype analysis.

2) World Rabbit Science Association: (WRSA) [http://world-rabbit-science.com]

International Association where researchers exchange knowledge and encourage teaching, scientific research, practical experimentation, the collection and publication of statistics and documents relating to the rabbit. Even have their own journal called “World Rabbit Science”

Website provides contact with researchers, professors and veterinarians working with rabbits.

Example: Dr. Myriam Kaplan-Pasternak, Doctorate Veterinary Medicine, University of California, myriamsemail@gmail.com

3) American Veterinary Medical Association [http://www.avma.org]

The American Veterinary Medical Association (AVMA), established in 1863, is a not-for-profit association representing more than 78,000 veterinarians working in private and corporate practice, government, industry, academia, and uniformed services. Excellent website into animal research and has a range of veterinary journals.

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== '''THE RABBIT (ORYCTOLAGUS CUNICULUS)''' ==

==Introduction==

[[File:Isidro_Martinez.jpg‎|left|175 px]]

Several characteristics of the rabbit make it an excellent model for study. This will be further explored in "The History of Model Use" section of this page. Many studies have resulted in the development and improvement of various micro-manipulation techniques such as the production of transgenic rabbits. Unlike many other species such as the chick or rat, relatively little is known about the development of a rabbit. Nevertheless, it is still an appropriate animal model as the results from many experiments are significant to that of other mammals, including humans. (55)

A rabbits potential for reproduction is high, breeding from the early stages of 3 to 4 months of age. A mature female rabbit can be pregnant from 6 to 8 months in a year, producing up to 30 to 40 young in this time. (56)

==History of Model Use==

'''WHY are we using rabbits?'''

ADVANTAGES
*Provides repeatability of animal model studies
*Large enough for single samples
*Many stocks/strains as animal models
*Easily managed
*Quality of immunologic products
*Ease of reproductive control

DISADVANTAGES
*Most colonies are a storehouse of diseases
*Extremely variable to responses to general anesthetics

'''Brief timeline of rabbit embryo model use'''

*1672- de Graaf found the Graffian follicle.
*1890- Walter Heape succeeded first mammalian embryo transfer
*1906- FT Lewis discovered the development of the lymphatic system in rabbit embryos.
*1941- Dr. Pincus succeeded in keeping rabbit embryos developing in the test
*1968- Edwards and Gardner successfully performed the first known embryo biopsy on rabbit embryos

=== Regnier de Graaf (1641–1673) ===
[[image:Ovary_Graaf.jpg|thumb|250px|left|drawing of ovary]]
[[File:Regnier de Graaf.jpg|right]]

'''Discovery of the Graafian Follicles'''

In 1672 de Graaf published ''The Generative Organs of Women'', which was primarily a study of development in the rabbit. When de Graaf discovered large, round welling on the ovaries of rabbits, he assumed they were mammalian eggs. De Graaf also described the corpus luteum.

He summarised the previous works from anatomists, but unable to experience the amazing benefits made by microscopy.
But Antonie van Leeuwenhoek (A microbiologist, 1632 - 1723) argued that the structures now known as Graafian follicles could not be eggs. Haller suggested that the egg might be formed by the coagulation of the fluid within the Graafian follicle. De Graaf noted that the “egg” did not contain a tiny embryo, but he thought it did contain the “germ” of the future organism. (3)

=== Walter Heape (1855-1928) ===
'''First case of embryo transfer experiments'''

On 27 April 1890, Walter Heape (a professor and physician at the University of Cambridge, England) transferred rabbit embryos from one mother to another. (7) One rabbit mother became pregnant and delivered young from the transferred embryos. This was the first mammalian embryo transfer experiment to be successfully completed. His embryo transfer work in perspective as it relates to other contributions of this pioneer in reproductive biology.(7)

In 1891, Walter Heape had been conducting research on reproduction in numerous animal species. Working with two species of rabbits, he flushed embryos from the rabbit fallopian tubes of one breed (Angora) and placed them into the uterus of a recently mated Belgian hare. In the resulting litter, there were 4 Belgians and 2 Angoras. Heape proved that it was possible to take preimplantation embryos and transfer them to a gestational carrier without affecting their development.(7)

===Dr. Gregory Goodwin Pincus (1903-1967) ===

'''Contraceptive pill'''

Dr. Pincus began studying hormonal biology and steroidal hormones early in his career. His first breakthrough came when he was able to produce in vitro fertilization in rabbits (by using chemicals) in 1934. Throughout their hormonal contraceptive research Pincus, along with reproductive physiologist Min Chueh Chang, found out progesterone would act as an inhibitor to ovulation. They co-invented the combined oral contraceptive pill.[2][6]

===Genetic Diagnosis===
In 1968, Robert Edwards and David Gardner reported the successful sexing of rabbit blastocysts, setting the first steps towards PGD (Preimplantation Genetic Diagnosis). It was not until the 1980s that human IVF was fully developed, which coincided with the breakthrough of the highly sensitive polymerase chain reaction (PCR) technology. Handyside and collaborators' first successful attempts at testing were in October 1989 with the first births in 1990 though the preliminary experiments had been published some years earlier. In these first cases, PCR was used for sex determination for patients carrying X-linked diseases.(12)

==Timeline of Embryo Development==

The following is a timeline, adapted from Cibelli (2002), of the main events of preimplantation development in rabbits. The time is measured in hours post-mating and shows the embryo stage (cell number) in each time scale.

[[File:Morula1.JPG|right|200 px|thumb|A day 2 early morula]]

'''12-14 hours:''' Oocyte; Fertilization

'''18-20 hours:''' Zygote; Pronuclear formation

'''24-26 hours:''' Two cell

'''30-32 hours:''' Four cell

'''38-40 hours:''' Eight cell; Maternal-zygotic transition

'''46-48 hours:''' Sixteen cell

'''54-56 hours:''' Morula (32 cell); Compaction and transport to uterus

'''64-66 hours:''' Compact morula (64 cell); Morula-blastocyst transition

'''76-78 hours:''' Early blastocyst (128 cell)

'''84-86 hours:''' Expanded blastocyst (256 cell); Blastocoels expansion

'''94-96 hours:''' Hatched blastocyst (512 cell); Hatching

The following shows a diagrammatic representation of the relative sizes of rabbit embryos. The sizes do not include the embryonic coverings such as the zona pellucida and mucin coat. This diagram has been adapted from Warner (2003).

[[File:Sizes.JPG]]

The following timelines show a comparison of the developmental stages between human and rabbit embryos. They have been adapted from Derelanko (2008). "The similarities of this developmental pattern in humans and rabbits, suggests that the same growth increment is required to achieve the same stage. The main difference observed between human rabbit gestational duration is due to the fetal growth phase. The reason for this may be due to birth weight, lifetime and the neural complexity of the species." (59)

[[File:Timeline_rabbit.JPG]]

The following timelines have been adapted from a study carried out by Beaudoin et al. on the development of rabbit embryos.

==='''Body Form'''===

'''8.5 days''': Embryo thickens. First somites appear. Rostral neuropore closes. Caudal neuropore remains open

'''9.5 days''': Dorsal curvature begins. Cardiac mass bulges under cephalic pole.

'''10.5 - 13.5 days''': Dorsal curvature increases. Body thickens. Softening of the cephalic domination straightens the embryo.

'''17.5 days''': Neck becomes visible.

==='''Limb Development'''===

''' 9.5 days''': Rostral limb bud appears

'''10.5 days''': Caudal limb bud appears

'''12.5 days''': Hand plate becomes present. Limbs become disposed.

'''13.5 days''': Foot plate and finger rays become visible.

'''14.5 days''': Rostral and caudal limbs become parallel.

'''15.5 days''': Elbow appears.

'''16.5 days''': Fingers start to elongate.

'''17.5 days''': Knee becomes visible

'''19.5 days''': Hands and feet merge on the midline. Three segments of limbs become distinguished.

==='''Abdominal Wall Development'''===

'''9.5 days''': Abdominal wall is limited to the embryonic pedicle under the cardiac mass.

'''13.5 days''': First intestinal loops appear in the umbilical cord.

'''14.5 days – 17.5''': Rapid intestinal development in the cord.

'''15.5 days''': Abdominal vesicles can be observed.

'''16.5 days''': Cecal bud becomes present outside the abdomen

'''18.5 days''': Bowel returns to the abdominal cavity and umbilical ring closes.

==='''Cephalic Development'''===

'''9.5 days''': One cerebral vesicle can be seen. Pharyngeal arches as optic vesicle are present.

'''10.5 days''': Three arches are distinguished in the cephalic pole.

'''11.5 days''': Three cerebral vesicles present. Optic plate is distinguished.

'''12.5 days''': Face develops nasal, maxillar and mandibular buds. Lens vesicle is closed. Five cerebral vesicles exist.

'''14.5 days''': The ear becomes refined. Face can be distinguished from the brow.

'''18.5 days''': Eyelid appears, covering the eyes.

==Staging==

The following stages have been adapted from Beaudoin et al. (2003). Table 1 represents at each age its corresponding stage defined by the Carnegie classification

{| class="wikitable" style="text-align:center; width: 800px; height:1000px" border="1"
|+'''Table 1. Rabbit developmental stages using Carnegie classification'''

|- style="height:50px"
! '''Stage''' !! '''Days''' !! '''Event''' !! '''Image'''
|- style="width:200px"
! width="50" | 10
| width="50" | 8.5 || First somites appear, rostral neuropore closes
|- style="height:75px"
! 12
| 9.5 || Rostral limb bud, embryonic pedicle, caudal neuropore closes, one cerebral vesicle, pharyngeal arches, completion of optic vesicle
| [[file: 9.5new.JPG|100px]]
|- style="height:75px"
! 13
| 10.5 || Dosral C-shaped curvature, caudal limb bud, prominent cardiac swelling, four pharyngeal arches
| [[file: 10.5new.JPG|100px]]
|- style="height:75px"
! 14
| 11.5 || Three cerebral vesicles, optic plate, mesonephric ridge
|- style="height:75px"
! 15
| 12.5 || Hand plate, wheel ray limbs, lens vesicle closes, five cerebral vesicles, facial buds, vertebrae
| [[file: 12.5new.JPG|100px]]
|- style="height:75px"
! 16
| 13.5 || Foot plate, finger rays, prominent liver, intestinal loops, auricular hillocks
| [[file: 13.5new.JPG|100px]]
|- style="height:100px"
! 19
| 14.5 || Cuboidal body, trunk straightens, parallel limbs, toe rays, modeled face, visible auricle
| [[file: 14.5new.JPG|100px]]
|- style="height:75px"
! 20
| 15.5 || Elbow, fingers elongate, notches between toe rays
| [[file: 15.5new.JPG|100px]]
|- style="height:75px"
! 21-22
| 16.5 || Toes free, cecal bud in intestinal hernia
| [[file: 16.5new.JPG|100px]]
|- style="height:75px"
! 22-23
| 17.5 || Knee, neck, eyelids
| [[file: 17.5new.JPG|100px]]
|- style="height:75px"
! 23
| 18.5 || Hands and feet join at the midline, closure of abdominal wall, eyelids cover eyes
| [[file: 18.5new.JPG|100px]]
|-
| colspan="4" align="center"| Following this stage fetal appearance is completed, organogenesis is achieved
|}

==Genetics==

===Sequencing===
The National Human Genome Research Institute selected the European rabbit (Oryctolagus cuniculus) for whole genome sequencing to enhance their understanding of the human genome and use it experimentally for an animal model for human disease. (8)

The rabbit has been sequenced twice by The Broad Institute as part of the mammalian genome project. It is now currently undergoing 7 more sequencing projects. Its sequencing is made by the Whole Genome Shotgun (WGS) and assembly method. (9) This is when genomic DNA is sheared into small pieces of approximately 2000 base pairs which are then cloned into plasmids and sequenced on both strands. Once the contig fragments are read, realigned and reassembled by computer algorithms, it will give the overall sequence. (10) (11) The image below shows diagramatically how the two types of sequencing are different. The same techniques are used for sequencing the human genome (in 2003). [A contig is a set of overlapping DNA segments, derived from a single source of genetic material, from which the complete sequence may be deduced.

The whole genome shotgun (WGS) has serious gaps, yet the information has already proven useful for immunological as well as in silico studies. Deeper 7x coverage started in September 2007. The NCBI Rabbit Genome Resources site has links to searches for genes in the assemblies of the 2x WGS sequence at Ensembl and UCSC.(12) [http://www.broadinstitute.org/models/europeanrabbit/ Rabbit Genome Project]

[[File:WGS_sequencing.gif‎|center|800 px]]

===Genome===
The Rabbit genome was published by two groups (9)
# Lindblad-Toh,K., Chang,J.L., Gnerre,S., Clamp,M. and Lander,E.S. published their admission of 84024 bases on May 5th 2005 to The Broad Institute (USA) by shotgun sequencing
# Di Palma,F., Heiman,D., Young,S., Gnerre,S., Johnson,J., Lander,E.S. and Lindblad-Toh,K. published their admission of 84024 bases on August 3rd 2009 to The Broad Institute (USA) by shotgun sequencing.
The rabbit's genome is sequenced and on display in the Nucleotide Data Bank. It is too long to produce here. A link to the data bank is provided: [http://www.ncbi.nlm.nih.gov/nuccore/256946799/ Rabbit Genome from the Nucleotide Data Bank]

[[File:8cellembryo.jpg|thumb|Individual mitochondria (arrowheads) of an 8cell Rabbit embryo]]

The rabbit genome was sequenced in 2005 by Ensembl and managed to produce: (13)
* 2,076,044,328 supercontigs (ordered Contigs with gaps)
* 495 Known protein-coding genes
* 11,357 Projected protein-coding genes
* 2,343 RNA genes
* 212,581 Gene exons
* 20,311 Gene transcripts

For further research the taxonomy ID number for the Rabbit is: 9986 [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=9986&lvl=3&lin=f&keep=1&srchmode=1&unlock/ Taxonomy Data]

===Mitochondrial Genome===
The mitochondiral genome (mtDNA) of the rabbit was sequenced on November 14th 2006 with 17245 base pairs/nucleotides in circular form. Apparently the "length is not absolute due to the presence of different numbers of repeated motifs in the control region".
PMID 9653643

The image to the right shows the mitochondria during cell division and multiplication in embryo development.

=== Chromosomes ===
Over the years there have been various data suggesting the diploid chromosomal number for the rabbit may range from 22-42. However through recent research and an abundance of trials suggest that the rabbit does indeed have 22 different chromosome pairs existing in each cell of the rabbit. (16)(17) The sex chromosomes of the rabbit are of X-Y type convincingly (17). In a study in Bombay it confirmed that a rabbit has 2n = 44 chromosomes. There were 21 pairs of autosomes, out of which 1 to 6 were metacentric, 7 to 11 submetacentric, 12 to 17 subtelocentric and 18 to 21 acrocentric, plus the sex chromosomes. The image to the left shows a female rabbit with no chromosomal abnormalities. (19)

'''Comparison to human chromosome:'''

Rabbit chromosomes 12, 19 and X were found to be completely homologous to human chromosomes 6, 17 and X, respectively. All other human chromosomes were homologous to two or sometimes three rabbit chromosomes. (14) Chromosome 12 was shorter than chromosomes 13 and 14. (15) The image below illustrates the human chromosome (2n = 46).

[[File:Drawn chromosome.jpg|left|400 px]]

[[File:Karyotypehuman.gif|right|500 px]]

'''Abnormalities'''

These are generally more apparent during early embryo development in blastocysts from delayed fertilization. Some examples of abnormal development include cases of: (18)
* hypoploidy; 1 chromosome missing from a pair (2n = 43),
* double hypoploidy; 2 chromosomes missing from 2 different pairs (2n = 42),
* mosaicism (different chromosomal makeup in some cells).

Another study also found these abnormalities as well as: (19)
* autosomal trisomy (3 autosomes per pair),
* triploidy (extra set of chromsomes),
* mixoploidy (unequal number of chromosome sets in adjacent cells), and
* short arm deletion (deletion of parts of chromosomes).

A specific abnormality occurring in rabbits is the x-linked tremor. There is a mutation in exon 2 of the prteolipid-protein (PLP 1) gene, corresponding to the end of the first potential transmembrane domain of the protein. This disorder affects myelination of the central nervous system. OMIA ID:12 [http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=full_report&list_uids=100009169&log$=omiamaingene| Gene:100009169]

==Abnormal Development==

Abnormal embryological development is a vast field of study that has been the subject of recent research papers. Our investigation of abnormal development in rabbit embryology will focus on abnormalities commonly found in both rabbit and human embryos. We will explore the nature of these abnormalities in both humans and rabbits.

[[File:Normal v Abnormal.jpg|right|300 px|thumb|Brain MRI of patient with Hydrocephalus (left) compared to a normal brain (right). An obvious increase in ventricular size and a significant decrease in brain size is present.]]
[[File:Ventricle_Expansion.jpg|right|300 px|thumb|CSF accumulation in ventricles of brain increasing intracranial pressure.The pressure from the expanding ventricles force the brain and skull to grow outwards abnormally.]]

'''Hydrocephalus'''

Annually, one in every 1000 children born in Australia have hydrocephalus. Hydrocephalus occurs when excessive cerebrospinal fluid (CSF) accumulates in the brain and can result in severe disability and even death because the disorder can result in complete or near complete destruction of the cerebral cortex (22).

Children born with hydrocephalus typically exhibit abnormally large head circumference and bulging cranial fontanels as a result of increased intracranial pressure on the brain from the accumulating CSF (22,23). As CSF accumulates in the ventricles and CSF compartments of the brain, it expands forcing the brain to grow outward. The outward growing brain places pressure on the skull which in turn also grows outwards giving rise to an abnormally large head circumference and bulging cranial fontanels (22,24). It is generally acknowledged that children with hydrocephalus have mental retardation, often to the degree of being “vegetative” (24).

The serious consequences of this disease mean that much research is necessary to unearth methods of prevention and effective treatment. One of the modes of studying hydrocephalus is to use the rabbit experimental model where hydrocephalus can be induced in rabbit embryo’s. The injection of silicone oil into the cisterna magna of the brain is one way of inducing hydrocephalus in the rabbit embryo. The silicone oil obstructs the normal flow of CSF resulting in CSF accumulation in the brain leading to hydrocephalus (25). Another method of inducing hydrocephalus in rabbit embryo’s is by intentional vitamin A deprivation of pregnant dams. The vitamin A deficiency results in raised intracranial CSF pressure and aqueduct stenosis causing poor circulation of CSF leading to hydrocephalus (26,27). Although the exact function of vitamin A on brain development and CSF regulation is not fully understood, it is clear that Vitamin A has an important role in brain development and its normal functioning (27).
[[File:Rabbithhdrocephalus.jpg|center|300 px|thumb|Young rabbit with hydrocephalus caused by Vitamin A deficiency. Note the abnormally shaped cranium inflamed in appearance.]]

[[File:SpinabifidaMeningocele1.jpg|right|300 px|thumb|Spina Bifida Meningocele has characteristic damage to the meninges of the spinal cord which are pushed out through an opening in the vertebrae as a cyst filled with CSF.]]
[[File:SpinaBifidaMyelomeningocele.jpg|right|300 px|thumb|Spina Bifida Myelomeningocele is the most severe form of spinabifida where the damaged spinal cord protrudes out with damaged meninges as a cyst filled with CSF.]]
[[File:SpinaBifidaOcculta1.jpg|right|300 px|thumb|Spina Bifida Occulta is the least severe as the spinal cord and meninges are undamaged.]]

'''Spina Bifida'''

In Australia, the risk of spina bifida is 1 in every 500 pregnancies. Spina bifida is a type of neural tube defect where vertebrae (which normally cover and protect the spinal cord) are not completely formed but are divided resulting in the defective spinal cord and its coverings to protrude through the opening (28,29).

There are three main types of Spina Bifida differentiated by their characteristic features:

1)Spina Bifida Meningocele characterized by normal spinal cord, divided outer vertebrae and meninges surrounding the spinal cord protruding from the divided vertebrae as a cyst (1,28).

2)Spina Bifida Myelomeningocele characterized by split outer vertebrae with spinal cord and its meninges protruding from the divided vertebrae as a cyst. Commonly found at lumbar vertebral level (1,28,29).

3)Spina Bifida Occulta characterized unfused vertebral arches and exposed vertebral canal. Spinal cord and its meninges still located in vertebral canal (1,28).

All forms of spina bifida are potentially fatal and in those where the spinal cord is damaged severe consequence arise including and paralysis and loss of sensation at and below the level of damage spinal cord damage (29,33). There is a lot of Spina bifida research using rabbit models to test the effective methods of correcting spina bifida. The occurrence of natural spina bifida in rabbits is rare and for experimental purposes it can be surgically created in rabbit fetuses during gestation (31,32). The process involves aesthetical sedation of the maternal rabbit at day 22 of gestation; a midline laparotomy performed and the desired type of spina bifida lesion created on the exposed fetus using forceps. Different methods for correcting spina bifida can then be tested and its effectiveness analysed (30,33,34).
[[File:Rabbitspinabifida1.jpg|center|350 px|thumb|Rabbit newborn with Spina Bifida. Note the unfused, divided vertebrae and exposed spinal cord.]]

'''Brachydactylia & Acheiropodia'''

[[File:Malformation1.jpg|right|150 px|thumb|Acheiropodia in rabbit characterized by amputations of the limbs and extremities.]]

[[File:Rabbitmalformation3.jpg|left|150 px|thumb|X-Ray study of rabbit limbs with malformed phalanges due to Brachydactylia.]]

Brachydactylia and Acheiropodia are genetic disorders characterized by skeletal malformation of the hands and feet (36,36). In Brachydactylia, the malformations commonly involve abnormal shortening of fingers and toes due to poorly formed or absent bones (35). Acheiropodia is characterized by more severe skeletal malformations including bilateral amputations of the distal upper and lower extremities as well as aplasia of the hands and feet. Although it is not fatal, the individual endures a very difficult life without hands and feet (37).

The inheritance mechanism of this diseases can has been studied through experiment using rabbits. Rabbits with abnormal genes coding for Brachydactylia and Acheiropodia are selected and bred to produce offspring with the disease (36). Brachydactylia and Acheiropodia are autosomal recessive disorders which means that two copies of an abnormal gene must be present in the affected individual in order for the disease to develop. Thus, each parent passes an abnormal gene to the offspring (35,36). The process of the malformation progresses from genotype to phenotype; small deletions on the chromosomes produce abnormal genes, the abnormal genes are then passed down to the offspring, the offspring that inherits two of the abnormal genes is unable to code for the correct proteins and as a result, there is failure in normal development of limb extremities in the embryo phenotype (37,38).

==Current Embryology Research==

There is currently great excitement in research involving rabbits in the fields of transgenesis, cloning and stem cells. We shall explore research in these areas by discovering some of the techniques used and how they have been applied to the rabbit model.

[[File:Trans1.jpg|right|170 px]]
[[File:Trans2.jpg|right|170 px]]
[[File:Trans3.jpg|right|170 px]]
[[File:Trans4.jpg|right|170 px]]
[[File:Trans5.jpg|right|170 px]]

'''Transgenic rabbit'''

A transgenic organism is one whose genome also contains genes from another species (39). The aim of creating a transgenic organism is to obtain a favorable characteristic in the organism’s phenotype (41). This desired characteristic of phenotype is obtained by altering the organism’s normal genotype to include the gene from another species with the desired characteristic (39,40).

The production of a transgenic organism involves several steps summarized below:

1) The chromosome and the desired gene on it are identified in an organism (39).

2) The gene is isolated from its DNA strand. This involves “cutting” it out of its DNA strand using enzymes called restriction endonucleases. The restriction endonucleases cut DNA at specific site so the desired gene can be removed from the DNA strand. The cut ends are known as “sticky ends” (39,40).

3) Separate DNA sequences for regulation sometimes have to be added to ensure the gene will work (40).

4) The gene is then inserted with a promoter sequence into the fertilized egg cell of a new organism producing recombinant DNA (39,44). To do this, firstly the new organism’s cell DNA must first be cut and the desired gene incorporated into it. The same enzymes are used to cut the new organism’s cell DNA because the DNA stands from the two different organisms will form matching sticky ends that will be attracted to and connect with each other in a process is called “annealing” (39,40,44).

5) DNA ligases are sealing enzymes found in all living organisms that help make and repair DNA (39,40). The DNA ligases are added to the annealed DNA fragments to help strengthen the bonds of the new recombinant DNA. The recombinant DNA is now transferred into the new organism’s fertilized egg by microinjection (44).

6) As the embryo develops and the recombinant genetic code read, new proteins are synthesized which code for the new desired phenotype characteristic in the transgenic organism (39,40).

Transgenic rabbits can be created in the laboratory by gene microinjection into the fertilized rabbit oocyte (44). In April 2000, a transgenic rabbit named Alba was born containing a gene from a Pacific Northwest jellyfish. The gene which was injected into a fertilized albino rabbit oocyte allows the rabbit to synthesize the green fluorescent protein (GFP) that is characteristic of the Pacific Northwest jellyfish. When illuminated correctly, Alba glows a bright green (43,46).

Transgenic rabbits have important research purposes. Transgenic rabbits can be created to model retinal degeneration (44). Retinal degeneration is a common problem with aging and diseases such as diabetes, and frequently leads to complete blindness (42). A genetic retinal degeneration disease called retinitis pigmentosa (RP) is created in these rabbits by introducing the “Pro347Leu” mutation of the rhodopsin gene into fertilized rabbit eggs (43,44). As the rabbit grows, it develops the disease which becomes progressively worse (45).
The use of these transgenic rabbits ultimately leads to better understanding of the disease and more effective treatments (42). [[File:Transgenic rabbit.jpg|center|250 px|thumb|"Alba" A trangenic rabbit with a gene from a Pacific Northwest jellyfish that allows it to synthesize the green fluorescent protein (GFP) of the jellyfish.]]

[[File:Crabbit 1.jpg|right|170 px]]
[[File:Rabbit2.jpg|right|170 px]]
[[File:Rabbit3.jpg|right|170 px]]
[[File:Crabbit 4.jpg|right|170 px]]

'''Cloning'''

Cloning is a method of producing genetically identical organisms. The principle of cloning relies on “tricking” an egg cell to begin rapidly dividing into an embryo (39). In the normal fertilization process, two haploid sex cells unite to form a diploid zygote which begins rapidly dividing into an embryo (40). By replacing the haploid egg cell nucleus with a diploid somatic cell nucleus, the egg cell is tricked into thinking it is fertilized and hence begins rapidly dividing to form an embryo (39,40,41).

The process of cloning involves several steps summarized as the following using a rabbit example:

1) A somatic cell is obtained from a rabbit and the nucleus removed (39).

2) An egg cell is obtained from a donor rabbit and the nucleus of the egg cell removed using an enucleation needle. The cell is now called an enucleated egg cell (egg cell without a nucleus) (39,41).

3) The nucleus of the somatic cell is inserted into the enucleated egg cell (41).

4) The cell is now stimulated to divide by applying pulses of electric current (39).

5) The rapidly dividing cell develops in culture for a few days forming the early embryo (40,41).

6) The embryo is then implanted into the uterus of another rabbit similar to the egg cell donor. This rabbit is called the surrogate mother (40,41).

7) The embryo develops and the surrogate mother gives birth to a rabbit fetus with near identical genotype of the somatic cell donor (the small genomic difference is caused by the fetus obtaining mitochondrial DNA from the egg cell donor) (39,41).

The cloning of rabbits has been achieved by inserting the diploid nucleus of a rabbit fibroblast (the principal cells in connective tissue) into an enucleated oocyte (49). There is currently much focus on the creation of controversial but revolutionary interspecies hybrid embryos where the nucleus from a human somatic cells are implanted into an enucleated egg cell of another animal (50). The resulting embryo (known as a chimera) will be almost completely human genotype but will have genome from the other animal (48). In 2003, scientists at the Shanghai Second Medical University fused human cell with rabbit eggs creating the first human-rabbit hybrid using the nucleus transfer technique. The hybrid embryo developed in culture for a few days before it was destroyed and the stem cells harvested (47,48). The purpose of the research into creating hybrid embryos is to provide researchers with human stem cells for experimentation into cures for diseases such as cystic fibrosis, Alzheimer’s and Motor Neuron disease as human stem cell are difficult to obtain (50).

[[File:Rabbit clone.jpg|center|450 px|thumb|(A) Cloned rabbits (5 month old) from nuclear transfer technique. (B) The male rabbit whose fibroblasts were used as the nuclear donors. The cloned rabbits have almost identical genome to the male donor.]]

'''Stem Cells'''
[[File:HES.jpg|right|200 px|thumb|Human Embryonic Stem cell (hES).]]
[[File:Rabbit knee.jpg|right|200 px|thumb|Stem cell induced cartilage repair of knee in rabbit.]]

Stem cells are unspecialized cells which are able to continuously reproduce themselves and under appropriate conditions, differentiate into all the various specialized cells of the organism such as cardiac cells, neurons and blood cells (39,40). Adults have a small number of stem cells when compared to a developing embryo and the stem cell of an embryo more easily obtained (41). Human embryonic stem cells (hES) derived from the inner mass of the preimplantation blastocyst have the potential to differentiate into all cell types in the human body and thus are valued by researchers (50). However, due to ethical and political issues, the obtaining and experimentation on human embryonic stem cells is difficult and alternate means are needed as stem cell provides potentially new treatments for a range of diseases (54).

Rabbits can be used both in the obtaining of stem cell for experimentation and also as recipients of stem cells to cure diseases. The human-rabbit hybrid embryo provides a method of obtaining stem cells for experimentation and these stem cells possess many similar properties to human stem cells, including expression of surface markers, special growth requirements, capabilities of self renewal, formation of embryonic body and differentiation into cells of all three germ layers (53).

Stem cell experimentation on rabbits also focuses on transplanting stem cell into rabbits to treat specific diseases. A study at Zhejiang University where a research team transplanted human mesenchymal stem cell into New Zealand white rabbits with myocardial infarction recoded regeneration of vascular structure and improvement in cardiac function. The research team noted the potential of stem cells in differentiating into specialized cardiac cells when subjected to the specific conditions of the rabbit heart (52).

Another study at Hallym University tested the effectiveness of transplanting mesenchymal stem cells from New Zealand white rabbits into damaged cartilage in the knees of other New Zealand white rabbits. In the experiment, mesenchymal stem cells were obtained from the rabbit bone marrow and injected into the knees of other rabbits that had cartilage in their knees surgically damaged. The research team were able to conclude notable cartilage recovery in the rabbits with the mesenchymal stem cell injection and the potential of mesenchymal stem cells to differentiate into fibroblasts, adipoblasts, osteoblasts and chondroblasts (51,53).

The findings in stem cell experimentation with in rabbits yielded positive results and potentially opens a new field of research in the use of stem cell to treat a range of diseases in humans.

==References==

# Dr Mark Hill 2009, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G [6]
# E.Horne Craigie, University of Toronto Press 1948, Bensley's Practical Anatomy of the Rabbit 8th Edition
# Ankum WM, Houtzager HL, Bleker OP (1996). "Reinier De Graaf (1641-1673) and the fallopian tube". Human Reproduction Update 2 (4): 365–9. doi:10.1093/humupd/2.4.365. PMID 9080233.
# Jocelyn HD, Setchell BP (December 1972). "Regnier de Graaf on the human reproductive organs. An annotated translation of Tractatus de Virorum Organis Generationi Inservientibus (1668) and De Mulierub Organis Generationi Inservientibus Tractatus Novus (1962)". Journal of Reproduction and Fertility. Supplement 17: 1–222.
# Jay, V. (2000). "A portrait in history. The legacy of Reinier de Graaf". Archives of Pathology & Laboratory Medicine 124(8): 1115–6.
# Lois N Magner. "A history of the Life Sciences" 3rd edition
# J. D. Biggers. (1991). Walter Heape, FRS: a pioneer in reproductive biology.Centenary of his embryo transfer experiments Laboratory of Human Reproduction and Reproductive Biology, and Department of Cellular and Molecular Physiology, Harvard Medical School, Boston, MA 02115, USA
# National Center for Biotechnology Information. (June 16, 2009). ''Rabbit Genome Resources'', Retrieved August 20, 2009, from [http://www.ncbi.nlm.nih.gov/projects/genome/guide/rabbit/ NCBI Rabbit Genome Site]
# The Broad Institute. (2008). ''Rabbit Genome Sequencing Project''. Retrieved only August 29, 2009, from [http://www.broadinstitute.org/models/europeanrabbit/ Rabbit Genome Sequencing Project]
# Campbell, M. A. (2002). ''Sequencing Whole Genomes: Hierarchical Shotgun Sequencing v. Shotgun Sequencing'' Retrieved August 31, 2009, from [http://www.bio.davidson.edu/courses/GENOMICS/method/shotgun.html/ Shotgun Sequencing - 1]
# Trivedi, B. (2000). ''Sequencing the Genome''. Retrieved September 4, 2009, from [http://www.genomenewsnetwork.org/articles/06_00/sequence_primer.shtml Shotgun Sequencing - 2]
# Mage, R. (2008). Rabbit genome sequencing update: genes of immunological interest found in the 2x genome assemblies, ENCODE, and the 7x trace archive. ''Journal of FASEB'' 22(Retrieved September 5, 2009, from [http://www.fasebj.org/cgi/content/meeting_abstract/22/2_MeetingAbstracts/559/ Rabbit Genome & its Immunological Interest]
# Ensembl (2009). ''Rabbit (Oryctolagus cuniculus)''. Retrieved September 5, 2009, from [http://www.ensembl.org/Oryctolagus_cuniculus/Info/Index/ Ensembl Genome Project]
# Korstanje, R. et al. (1999) Complete homology maps of the rabbit (Oryctolagus cuniculus) and human by reciprocal chromosome painting. ''Cytogenetics and cell genetics'' ''86''(3-4), 317-322. Retrieved September 6, 2009, from [http://cat.inist.fr/?aModele=afficheN&cpsidt=1189693/ Complete homology maps of the rabbit Article] "PMID 10575232"
# Brunner, R., Knopp, A., Rudolph, W. (n.d). Rabbit chromosome analysis by image processing. ''Journal of Applied Rabbit Research''.
# DebMark Rabbit Education Resource (2006). ''Rabbit Genetics''. Retrieved September 6, 2009, from [http://www.debmark.com/rabbits/genetics.htm/ Rabbit Genetics]
# Painter, T. (2009) Studies in mammalian spermatogenesis VI. The chromosomes of the rabbit. ''Journal of Morphology''. ''43''(1): 1-43.
# Hofsaess, F., and Meacham, T. ( 1995) Chromosome abnormalities of early rabbit embryos. ''Journal of Experimental Zoology''. ''177'' (1): 9-11 [http://www3.interscience.wiley.com/journal/110490865/abstract/ Chromosome abnormalities]
# Martin-Deleon, P., Shaver, E., and Gammal, E. (1973) Chromosome abnormalities in rabbit blastocysts resulting from spermatozoa aged in the male tract. ''Fertility and Sterility''. ''24''(3):212-219.
# Patil, M. et al (2004) Chromosome analysis of domestic rabbit. ''The Journal of Bombay Veterinary College''. ''12'' (1 and 2)
#Biggers J.D (1991) Walter Heape FRS: a pioneer in reproductive biology. centenary of his embryo transfer experments.''Journals of reproduction and fertility''. ''93''(1)
# Stoodley, M (2006). Hydrocephalus. Prince of Wales Clinical School. Retrieved from [http://www.brainaustralia.org.au/AZ_of_Brain_Disorders/hydrocephalus]
# National Institute of Neurological Disorders and Stroke (2008, February). Hydrocephalus Fact Sheet. Retrieved from [http://www.ninds.nih.gov/disorders/hydrocephalus/detail_hydrocephalus.htm]
# Lewin, R (1999). Is Your Brain Really Necessary?. 24) Developmental Medicine & Child Neurology, 41. Retrieved from [http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=176431]
# Bigio, M.R, & Bruni J.E (1991). Silicone oil-induced hydrocephalus in the rabbit . Child's Nervous System, 7(2), Retrieved from [http://www.springerlink.com/content/b011477724837152/]
# Geelen, J.A (1974). A case of hydrocephalus and meningoencephalocele in a rabbit, caused by aqueductal malformation. Laboratory Animals, 8(2), Retrieved from [http://la.rsmjournals.com/cgi/content/abstract/8/2/167]
# LAMMINGX, G.E (1954). 27) Hydrocephalus in Young Rabbits Associated with Maternal Vitamin A Deficiency. British Journal of Nutrition, 8(2), Retrieved from [http://journals.cambridge.org/download.php?file=%2FBJN%2FBJN8_04%2FS0007114554000554a.pdf&code=10bb1dbc4a9e57a091f4e05f6aebbcf2]
# Carney, A (2008, February ). Spina bifida. Retrieved from [http://www.spinabifida.asn.au/]
# Better Health Channel (2008, October ). Spina bifida explained . Retrieved from [http://www.betterhealth.vic.gov.au/bhcv2/bhcarticles.nsf/pages/Spina_bifida_explained]
# Peeters, M.C, Viebahn, C, & Hekking, J.W (1998). Neurulation in the rabbit embryo . Anatomy and Embryology, 197(3), Retrieved from [http://www.springerlink.com/content/1efyteewgetjlwyg/]
# George, T.M, & Fuh E (2003). Review of Animal Models of Surgically Induced Spinal Neural Tube Defects: Implications for fetal surgery. Pediatric Neurosurgery , 39(2), Retrieved from [http://content.karger.com/produktedb/produkte.asp?typ=fulltext&file=PNE2003039002081]
# Pedreira, D.A, & Valente P.R (2002). A Different Technique to Create a 'Myelomeningocele-Like' Defect in the Fetal Rabbit. Fetal diagnosis and therapy, 17(6), Retrieved from [http://content.karger.com/ProdukteDB/produkte.asp?Doi=65388]
# Patten, B.M (1953). Embryological stages in the establishing of myeloschisis with spina bifida. The American journal of anatomy, 93(3), Retrieved from [http://deepblue.lib.umich.edu/handle/2027.42/49611]
# Pedreira, D.A, & Valente P.R (2003). Successful Fetal Surgery for the Repair of a 'Myelomeningocele-Like' Defect Created in the Fetal Rabbit. Fetal Diagnosis and Therapy, 18. Retrieved from [http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowPDF&ProduktNr=224239&Ausgabe=229041&ArtikelNr=69378]
# Lecklitner, M.L, & Douglas K.P (1986). Osteoscintigraphy and brachydactylia of the hand . European Journal of Nuclear Medicine and Molecular Imaging, 12(9), Retrieved from [http://www.springerlink.com/content/t82l77282x579102/]
# Greene, H.S, & Saxton J.A (1938). HEREDITARY BRACHYDACTYLIA AND ALLIED. ABNORMALITIES IN THE RABBIT. THE JOURNAL OF EXPERIMENTAL MEDICINE , 69. Retrieved from [http://jem.rupress.org/cgi/reprint/69/2/301.pdf]
# P. Ianakiev, M. van Baren, M. Daly, S. Toledo, M. Cavalcanti, J. Neto, E. Silveira, A. Freire-Maia, P. Heutink, M. Kilpatrick. Acheiropodia Is Caused by a Genomic Deletion in C7orf2, the Human Orthologue of the Lmbr1 Gene. The American Journal of Human Genetics, 68. Retrieved from [http://linkinghub.elsevier.com/retrieve/pii/S0002929707624707]
# Walbaum, R, Hazard, C, & Cordier, R (1976). Brachydactylia with symphalangism, probably autosomal recessive . Human Genetics, 33(2), Retrieved from [http://www.springerlink.com/content/m630p6880661486n]
# Campbell, N.A, & Reece, J.B (2002). Biology 6th Edition. USA: Benjamin Cummings.
# Solomon, E.P, Berg, L.R, & Martin, D.W (2002). Biology 6th Edition. USA: Thompson Learning.
# Glanville, A.R (2008). Scientifica. NSW, Australia: Millennium House.
# Lund, R.D (2008). Saving Vision with Skin Cells. Retrieved from [http://www.blindness.org]
# Jones, B.W, & Marc R.E (2008). Computational Molecular Phenotyping and Excitation Mapping in the P347L. Retinal Degeneration , (2986), Retrieved from [http://prometheus.med.utah.edu/]
# Kondo, M, Sakai, T, & Ueno, S (2009). Generation of a Transgenic Rabbit Model of Retinal Degeneration. Investigative Ophthalmology and Visual Science, 50. Retrieved from [http://www.iovs.org/cgi]
# Punzo, C, Chen, B, & Roesch, K (2009). PHOTORECEPTOR DEATH IN MOUSE MODELS OF RETINITIS PIGMENTOSA. Retrieved from [http://genepath.med.harvard.edu]
# Zimmer, M (2008). Alba. Retrieved from [http://www.conncoll.edu/ccacad/zimmer/GFP-ww/cooluses8.html]
# Scott, C (2006, May 1). Chimeras in the crosshairs. Nature Biotechnology , 24, Retrieved from [http://www.nature.com/nbt/journal/v24/n5/abs/nbt0506-487.html]
# Mott, M (2005, January 25). Animal-Human Hybrids Spark Controversy. National Geographic News, Retrieved from [http://theyfly.com/PDF/Nat.%20Geo.%20Animal-Human%20Hybrids.pdf]
# Li, S, & Chen X (2006). Rabbits generated from fibroblasts through nuclear transfer . Society for Reproduction and Fertility, 131. Retrieved from [http://www.reproduction-online.org/cgi/reprint/131/6/1085]
# Minger, S (2007). Interspecies SCNT derived human embryos. Regenerative Medicine, 2(2), Retrieved from [http://www.futuremedicine.com]
# Koga, H, Shimaya, M, & Muneta, T (2008). Local adherent technique for transplanting mesenchymal stem cells as a potential treatment of cartilage defect. Arthritis Research & Therapy, 10(4), Retrieved from [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2575632]
# Wang, J, Li, C, & Sun, Y (2005). Human bone marrow-derived mesenchymal stem cells transplanted into damaged rabbit heart to improve heart function. Journal of Zhejiang University Science, 6(4), Retrieved from [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1389731]
# Chen, Y, Liu, A, & Mao, W (2003). Embryonic stem cells generated by nuclear transfer of human somatic nuclei into rabbit oocytes. Cell Research , 13(4), Retrieved from [http://www.nature.com]
# Bethesda (2009, September 23). Stem Cell Information. Retrieved from [http://stemcells.nih.gov]
# Cibelli, J. B. (2002). Principles of cloning Amsterdam. Academic Press
# European rabbit (oryctolagus cuniculus) Retrieved 9/21/2009, 2009, from http://www.feral.org.au/content/species/rabbit.cfm
# Warner, S. (2003). Inositol transport in preimplantation rabbit embryos: Effects of embryo stage, sodium, osmolality and metabolic inhibitors Reproduction, 125(4), 479-493.
# Derelanko, M. J. (2008). The toxicologist's pocket handbook, second edition Informa HealthCare
# Beaudoin, S., Barbet, P., & Bargy, F. (2003). Developmental stages in the rabbit embryo: Guidelines to choose an appropriate experimental model Fetal Diagnosis and Therapy, 18(6), 422-427.

==Glossary==

Anesthetic - A drug that causes temporary loss of bodily sensations

Aplasia - The absence or defective development of a tissue or organ

Blastocyst - A stage of embryo development that occurs about five days after fertilisation when the embryo contains quite a few cells

Caudal - Situated towards the inferior or posterior end of the body

Cephalic - Relating to the head

Cerebral Aqueduct - A canal filled with cerebrospinal fluid within the midbrain

Cerebral Cortex - The layer of unmyelinated neurons (the grey matter) forming the cortex of the cerebrum of the brain

Cerebro Spinal Fluid (CSF) - A watery fluid which flows in the cavities within the brain and around the surface of the brain and spinal cord

Chromosome - Microscopic carriers of genetic material, composed of deoxyribonucleic acid (DNA) and proteins and appearing as rods under a microscope

Cisterna Magna - is one of three principal openings in the subarachnoid space between the arachnoid and pia mater layers of the meninges surrounding the brain

Diploid - A full set of genetic material, consisting of paired chromosomes one chromosome from each parental set

Dorsal - Position towards the back

Fontanel - Membranous gap between the bones of the cranium in an infant or fetus

Genome - All genetic information, the entire genetic complement and all of the hereditary material possessed by an organism. Made up of both chromosomal genome (inside the nucleus of the cell in the familiar form of chromosomes) and mitochondrial genome (outside the nucleus in the cytoplasm of the cell, usually in the form of one round chromosome (the mitochondrial chromosome))

Genotype - The genetic makeup of an organism

Glucocorticoids - A class of steroid hormones that bind to the glucocorticoid receptor (GR), which is present in almost every vertebrate

Haploid - A single set of chromosomes (half the full set of genetic material)

Laparotomy- Surgical incision into the abdominal wall; often done to examine abdominal organs

Ligases - Group of enzymes that catalyze the binding of two molecules

Oocyte - A female gametocyte that develops into an ovum after two meiotic divisions

Phenotype - The observable traits or characteristics of an organism, for example hair color, weight, or the presence or absence of a disease.

Pronuclear - Haploid nucleus before fusion of nuclei in fertilisation

Restriction Endonucleases - Enzymes that recognize and cleave specific DNA sequences, generating either blunt or single-stranded (sticky) ends

Retina - The thin layer of cells at the back of the eyeball where light is converted into neural signals sent to the brain

Rostral - Situated toward the oral and nasal region

Somite - Blocks of mesoderm on either side of the notochord and neural tube during development of the vertebrate embryo. Develop into muscles and vertebrae

Stenosis - Abnormal narrowing of a bodily canal or passageway

Weaning - Young become accustom to nourishment other than suckling

==Links to Research Laboratories and Researchers==

1) Transgenic lab: [http://www.dnavision.be/index.php]

Involved in development of transgenic organisms, DNA construction and phenotype analysis.

2) World Rabbit Science Association: (WRSA) [http://world-rabbit-science.com]

International Association where researchers exchange knowledge and encourage teaching, scientific research, practical experimentation, the collection and publication of statistics and documents relating to the rabbit. Even have their own journal called “World Rabbit Science”

Website provides contact with researchers, professors and veterinarians working with rabbits.

Example: Dr. Myriam Kaplan-Pasternak, Doctorate Veterinary Medicine, University of California, myriamsemail@gmail.com

3) American Veterinary Medical Association [http://www.avma.org]

The American Veterinary Medical Association (AVMA), established in 1863, is a not-for-profit association representing more than 78,000 veterinarians working in private and corporate practice, government, industry, academia, and uniformed services. Excellent website into animal research and has a range of veterinary journals.

{{Template:Projects09}}
[[Category:Rabbit]]
[[File:Example.jpg]]

2009 Group Project 1

2009-10-14T12:18:29Z

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[[File:Rabbits.png|right|400 px]]

== '''THE RABBIT (ORYCTOLAGUS CUNICULUS)''' ==

==Introduction==

[[File:Isidro_Martinez.jpg‎|left|175 px]]

Several characteristics of the rabbit make it an excellent model for study. This will be further explored in "The History of Model Use" section of this page. Many studies have resulted in the development and improvement of various micro-manipulation techniques such as the production of transgenic rabbits. Unlike many other species such as the chick or rat, relatively little is known about the development of a rabbit. Nevertheless, it is still an appropriate animal model as the results from many experiments are significant to that of other mammals, including humans. (55)

A rabbits potential for reproduction is high, breeding from the early stages of 3 to 4 months of age. A mature female rabbit can be pregnant from 6 to 8 months in a year, producing up to 30 to 40 young in this time. (56)

==History of Model Use==

'''WHY are we using rabbits?'''

ADVANTAGES
*Provides repeatability of animal model studies
*Large enough for single samples
*Many stocks/strains as animal models
*Easily managed
*Quality of immunologic products
*Ease of reproductive control

DISADVANTAGES
*Most colonies are a storehouse of diseases
*Extremely variable to responses to general anesthetics

'''Brief timeline of rabbit embryo model use'''

*1672- de Graaf found the Graffian follicle.
*1890- Walter Heape succeeded first mammalian embryo transfer
*1906- FT Lewis discovered the development of the lymphatic system in rabbit embryos.
*1941- Dr. Pincus succeeded in keeping rabbit embryos developing in the test
*1968- Edwards and Gardner successfully performed the first known embryo biopsy on rabbit embryos

=== Regnier de Graaf (1641–1673) ===
[[image:Ovary_Graaf.jpg|thumb|250px|left|drawing of ovary]]
[[File:Regnier de Graaf.jpg|right]]

'''Discovery of the Graafian Follicles'''

In 1672 de Graaf published ''The Generative Organs of Women'', which was primarily a study of development in the rabbit. When de Graaf discovered large, round welling on the ovaries of rabbits, he assumed they were mammalian eggs. De Graaf also described the corpus luteum.

He summarised the previous works from anatomists, but unable to experience the amazing benefits made by microscopy.
But Antonie van Leeuwenhoek (A microbiologist, 1632 - 1723) argued that the structures now known as Graafian follicles could not be eggs. Haller suggested that the egg might be formed by the coagulation of the fluid within the Graafian follicle. De Graaf noted that the “egg” did not contain a tiny embryo, but he thought it did contain the “germ” of the future organism. (3)

=== Walter Heape (1855-1928) ===
'''First case of embryo transfer experiments'''

On 27 April 1890, Walter Heape (a professor and physician at the University of Cambridge, England) transferred rabbit embryos from one mother to another. (7) One rabbit mother became pregnant and delivered young from the transferred embryos. This was the first mammalian embryo transfer experiment to be successfully completed. His embryo transfer work in perspective as it relates to other contributions of this pioneer in reproductive biology.(7)

In 1891, Walter Heape had been conducting research on reproduction in numerous animal species. Working with two species of rabbits, he flushed embryos from the rabbit fallopian tubes of one breed (Angora) and placed them into the uterus of a recently mated Belgian hare. In the resulting litter, there were 4 Belgians and 2 Angoras. Heape proved that it was possible to take preimplantation embryos and transfer them to a gestational carrier without affecting their development.(7)

===Dr. Gregory Goodwin Pincus (1903-1967) ===

'''Contraceptive pill'''

Dr. Pincus began studying hormonal biology and steroidal hormones early in his career. His first breakthrough came when he was able to produce in vitro fertilization in rabbits (by using chemicals) in 1934. Throughout their hormonal contraceptive research Pincus, along with reproductive physiologist Min Chueh Chang, found out progesterone would act as an inhibitor to ovulation. They co-invented the combined oral contraceptive pill.[2][6]

===Genetic Diagnosis===
In 1968, Robert Edwards and David Gardner reported the successful sexing of rabbit blastocysts, setting the first steps towards PGD (Preimplantation Genetic Diagnosis). It was not until the 1980s that human IVF was fully developed, which coincided with the breakthrough of the highly sensitive polymerase chain reaction (PCR) technology. Handyside and collaborators' first successful attempts at testing were in October 1989 with the first births in 1990 though the preliminary experiments had been published some years earlier. In these first cases, PCR was used for sex determination for patients carrying X-linked diseases.(12)

==Timeline of Embryo Development==

The following is a timeline, adapted from Cibelli (2002), of the main events of preimplantation development in rabbits. The time is measured in hours post-mating and shows the embryo stage (cell number) in each time scale.

[[File:Morula1.JPG|right|200 px|thumb|A day 2 early morula]]

'''12-14 hours:''' Oocyte; Fertilization

'''18-20 hours:''' Zygote; Pronuclear formation

'''24-26 hours:''' Two cell

'''30-32 hours:''' Four cell

'''38-40 hours:''' Eight cell; Maternal-zygotic transition

'''46-48 hours:''' Sixteen cell

'''54-56 hours:''' Morula (32 cell); Compaction and transport to uterus

'''64-66 hours:''' Compact morula (64 cell); Morula-blastocyst transition

'''76-78 hours:''' Early blastocyst (128 cell)

'''84-86 hours:''' Expanded blastocyst (256 cell); Blastocoels expansion

'''94-96 hours:''' Hatched blastocyst (512 cell); Hatching

The following shows a diagrammatic representation of the relative sizes of rabbit embryos. The sizes do not include the embryonic coverings such as the zona pellucida and mucin coat. This diagram has been adapted from Warner (2003).

[[File:Sizes.JPG]]

The following timelines show a comparison of the developmental stages between human and rabbit embryos. They have been adapted from Derelanko (2008). "The similarities of this developmental pattern in humans and rabbits, suggests that the same growth increment is required to achieve the same stage. The main difference observed between human rabbit gestational duration is due to the fetal growth phase. The reason for this may be due to birth weight, lifetime and the neural complexity of the species." (59)

[[File:Timeline_rabbit.JPG]]

The following timelines have been adapted from a study carried out by Beaudoin et al. on the development of rabbit embryos.

==='''Body Form'''===

'''8.5 days''': Embryo thickens. First somites appear. Rostral neuropore closes. Caudal neuropore remains open

'''9.5 days''': Dorsal curvature begins. Cardiac mass bulges under cephalic pole.

'''10.5 - 13.5 days''': Dorsal curvature increases. Body thickens. Softening of the cephalic domination straightens the embryo.

'''17.5 days''': Neck becomes visible.

==='''Limb Development'''===

''' 9.5 days''': Rostral limb bud appears

'''10.5 days''': Caudal limb bud appears

'''12.5 days''': Hand plate becomes present. Limbs become disposed.

'''13.5 days''': Foot plate and finger rays become visible.

'''14.5 days''': Rostral and caudal limbs become parallel.

'''15.5 days''': Elbow appears.

'''16.5 days''': Fingers start to elongate.

'''17.5 days''': Knee becomes visible

'''19.5 days''': Hands and feet merge on the midline. Three segments of limbs become distinguished.

==='''Abdominal Wall Development'''===

'''9.5 days''': Abdominal wall is limited to the embryonic pedicle under the cardiac mass.

'''13.5 days''': First intestinal loops appear in the umbilical cord.

'''14.5 days – 17.5''': Rapid intestinal development in the cord.

'''15.5 days''': Abdominal vesicles can be observed.

'''16.5 days''': Cecal bud becomes present outside the abdomen

'''18.5 days''': Bowel returns to the abdominal cavity and umbilical ring closes.

==='''Cephalic Development'''===

'''9.5 days''': One cerebral vesicle can be seen. Pharyngeal arches as optic vesicle are present.

'''10.5 days''': Three arches are distinguished in the cephalic pole.

'''11.5 days''': Three cerebral vesicles present. Optic plate is distinguished.

'''12.5 days''': Face develops nasal, maxillar and mandibular buds. Lens vesicle is closed. Five cerebral vesicles exist.

'''14.5 days''': The ear becomes refined. Face can be distinguished from the brow.

'''18.5 days''': Eyelid appears, covering the eyes.

==Staging==

The following stages have been adapted from Beaudoin et al. (2003). Table 1 represents at each age its corresponding stage defined by the Carnegie classification

{| class="wikitable" style="text-align:center; width: 800px; height:1000px" border="1"
|+'''Table 1. Rabbit developmental stages using Carnegie classification'''

|- style="height:50px"
! '''Stage''' !! '''Days''' !! '''Event''' !! '''Image'''
|- style="width:200px"
! width="50" | 10
| width="50" | 8.5 || First somites appear, rostral neuropore closes
|- style="height:75px"
! 12
| 9.5 || Rostral limb bud, embryonic pedicle, caudal neuropore closes, one cerebral vesicle, pharyngeal arches, completion of optic vesicle
| [[file: 9.5new.JPG|100px]]
|- style="height:75px"
! 13
| 10.5 || Dosral C-shaped curvature, caudal limb bud, prominent cardiac swelling, four pharyngeal arches
| [[file: 10.5new.JPG|100px]]
|- style="height:75px"
! 14
| 11.5 || Three cerebral vesicles, optic plate, mesonephric ridge
|- style="height:75px"
! 15
| 12.5 || Hand plate, wheel ray limbs, lens vesicle closes, five cerebral vesicles, facial buds, vertebrae
| [[file: 12.5new.JPG|100px]]
|- style="height:75px"
! 16
| 13.5 || Foot plate, finger rays, prominent liver, intestinal loops, auricular hillocks
| [[file: 13.5new.JPG|100px]]
|- style="height:100px"
! 19
| 14.5 || Cuboidal body, trunk straightens, parallel limbs, toe rays, modeled face, visible auricle
| [[file: 14.5new.JPG|100px]]
|- style="height:75px"
! 20
| 15.5 || Elbow, fingers elongate, notches between toe rays
| [[file: 15.5new.JPG|100px]]
|- style="height:75px"
! 21-22
| 16.5 || Toes free, cecal bud in intestinal hernia
| [[file: 16.5new.JPG|100px]]
|- style="height:75px"
! 22-23
| 17.5 || Knee, neck, eyelids
| [[file: 17.5new.JPG|100px]]
|- style="height:75px"
! 23
| 18.5 || Hands and feet join at the midline, closure of abdominal wall, eyelids cover eyes
| [[file: 18.5new.JPG|100px]]
|-
| colspan="4" align="center"| Following this stage fetal appearance is completed, organogenesis is achieved
|}

==Genetics==

===Sequencing===
The National Human Genome Research Institute selected the European rabbit (Oryctolagus cuniculus) for whole genome sequencing to enhance their understanding of the human genome and use it experimentally for an animal model for human disease. (8)

The rabbit has been sequenced twice by The Broad Institute as part of the mammalian genome project. It is now currently undergoing 7 more sequencing projects. Its sequencing is made by the Whole Genome Shotgun (WGS) and assembly method. (9) This is when genomic DNA is sheared into small pieces of approximately 2000 base pairs which are then cloned into plasmids and sequenced on both strands. Once the contig fragments are read, realigned and reassembled by computer algorithms, it will give the overall sequence. (10) (11) The image below shows diagramatically how the two types of sequencing are different. The same techniques are used for sequencing the human genome (in 2003). [A contig is a set of overlapping DNA segments, derived from a single source of genetic material, from which the complete sequence may be deduced.

The whole genome shotgun (WGS) has serious gaps, yet the information has already proven useful for immunological as well as in silico studies. Deeper 7x coverage started in September 2007. The NCBI Rabbit Genome Resources site has links to searches for genes in the assemblies of the 2x WGS sequence at Ensembl and UCSC.(12) [http://www.broadinstitute.org/models/europeanrabbit/ Rabbit Genome Project]

[[File:WGS_sequencing.gif‎|center|800 px]]

===Genome===
The Rabbit genome was published by two groups (9)
# Lindblad-Toh,K., Chang,J.L., Gnerre,S., Clamp,M. and Lander,E.S. published their admission of 84024 bases on May 5th 2005 to The Broad Institute (USA) by shotgun sequencing
# Di Palma,F., Heiman,D., Young,S., Gnerre,S., Johnson,J., Lander,E.S. and Lindblad-Toh,K. published their admission of 84024 bases on August 3rd 2009 to The Broad Institute (USA) by shotgun sequencing.
The rabbit's genome is sequenced and on display in the Nucleotide Data Bank. It is too long to produce here. A link to the data bank is provided: [http://www.ncbi.nlm.nih.gov/nuccore/256946799/ Rabbit Genome from the Nucleotide Data Bank]

[[File:8cellembryo.jpg|thumb|Individual mitochondria (arrowheads) of an 8cell Rabbit embryo]]

The rabbit genome was sequenced in 2005 by Ensembl and managed to produce: (13)
* 2,076,044,328 supercontigs (ordered Contigs with gaps)
* 495 Known protein-coding genes
* 11,357 Projected protein-coding genes
* 2,343 RNA genes
* 212,581 Gene exons
* 20,311 Gene transcripts

For further research the taxonomy ID number for the Rabbit is: 9986 [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=9986&lvl=3&lin=f&keep=1&srchmode=1&unlock/ Taxonomy Data]

===Mitochondrial Genome===
The mitochondiral genome (mtDNA) of the rabbit was sequenced on November 14th 2006 with 17245 base pairs/nucleotides in circular form. Apparently the "length is not absolute due to the presence of different numbers of repeated motifs in the control region".
PMID 9653643

The image to the right shows the mitochondria during cell division and multiplication in embryo development.

=== Chromosomes ===
Over the years there have been various data suggesting the diploid chromosomal number for the rabbit may range from 22-42. However through recent research and an abundance of trials suggest that the rabbit does indeed have 22 different chromosome pairs existing in each cell of the rabbit. (16)(17) The sex chromosomes of the rabbit are of X-Y type convincingly (17). In a study in Bombay it confirmed that a rabbit has 2n = 44 chromosomes. There were 21 pairs of autosomes, out of which 1 to 6 were metacentric, 7 to 11 submetacentric, 12 to 17 subtelocentric and 18 to 21 acrocentric, plus the sex chromosomes. The image to the left shows a female rabbit with no chromosomal abnormalities. (19)

'''Comparison to human chromosome:'''

Rabbit chromosomes 12, 19 and X were found to be completely homologous to human chromosomes 6, 17 and X, respectively. All other human chromosomes were homologous to two or sometimes three rabbit chromosomes. (14) Chromosome 12 was shorter than chromosomes 13 and 14. (15) The image below illustrates the human chromosome (2n = 46).

[[File:Drawn chromosome.jpg|left|400 px]]

[[File:Karyotypehuman.gif|right|500 px]]

'''Abnormalities'''

These are generally more apparent during early embryo development in blastocysts from delayed fertilization. Some examples of abnormal development include cases of: (18)
* hypoploidy; 1 chromosome missing from a pair (2n = 43),
* double hypoploidy; 2 chromosomes missing from 2 different pairs (2n = 42),
* mosaicism (different chromosomal makeup in some cells).

Another study also found these abnormalities as well as: (19)
* autosomal trisomy (3 autosomes per pair),
* triploidy (extra set of chromsomes),
* mixoploidy (unequal number of chromosome sets in adjacent cells), and
* short arm deletion (deletion of parts of chromosomes).

A specific abnormality occurring in rabbits is the x-linked tremor. There is a mutation in exon 2 of the prteolipid-protein (PLP 1) gene, corresponding to the end of the first potential transmembrane domain of the protein. This disorder affects myelination of the central nervous system. OMIA ID:12 [http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=full_report&list_uids=100009169&log$=omiamaingene| Gene:100009169]

==Abnormal Development==

Abnormal embryological development is a vast field of study that has been the subject of recent research papers. Our investigation of abnormal development in rabbit embryology will focus on abnormalities commonly found in both rabbit and human embryos. We will explore the nature of these abnormalities in both humans and rabbits.

[[File:Normal v Abnormal.jpg|right|300 px|thumb|Brain MRI of patient with Hydrocephalus (left) compared to a normal brain (right). An obvious increase in ventricular size and a significant decrease in brain size is present.]]
[[File:Ventricle_Expansion.jpg|right|300 px|thumb|CSF accumulation in ventricles of brain increasing intracranial pressure.The pressure from the expanding ventricles force the brain and skull to grow outwards abnormally.]]

'''Hydrocephalus'''

Annually, one in every 1000 children born in Australia have hydrocephalus. Hydrocephalus occurs when excessive cerebrospinal fluid (CSF) accumulates in the brain and can result in severe disability and even death because the disorder can result in complete or near complete destruction of the cerebral cortex (22).

Children born with hydrocephalus typically exhibit abnormally large head circumference and bulging cranial fontanels as a result of increased intracranial pressure on the brain from the accumulating CSF (22,23). As CSF accumulates in the ventricles and CSF compartments of the brain, it expands forcing the brain to grow outward. The outward growing brain places pressure on the skull which in turn also grows outwards giving rise to an abnormally large head circumference and bulging cranial fontanels (22,24). It is generally acknowledged that children with hydrocephalus have mental retardation, often to the degree of being “vegetative” (24).

The serious consequences of this disease mean that much research is necessary to unearth methods of prevention and effective treatment. One of the modes of studying hydrocephalus is to use the rabbit experimental model where hydrocephalus can be induced in rabbit embryo’s. The injection of silicone oil into the cisterna magna of the brain is one way of inducing hydrocephalus in the rabbit embryo. The silicone oil obstructs the normal flow of CSF resulting in CSF accumulation in the brain leading to hydrocephalus (25). Another method of inducing hydrocephalus in rabbit embryo’s is by intentional vitamin A deprivation of pregnant dams. The vitamin A deficiency results in raised intracranial CSF pressure and aqueduct stenosis causing poor circulation of CSF leading to hydrocephalus (26,27). Although the exact function of vitamin A on brain development and CSF regulation is not fully understood, it is clear that Vitamin A has an important role in brain development and its normal functioning (27).
[[File:Rabbithhdrocephalus.jpg|center|300 px|thumb|Young rabbit with hydrocephalus caused by Vitamin A deficiency. Note the abnormally shaped cranium inflamed in appearance.]]

[[File:SpinabifidaMeningocele1.jpg|right|300 px|thumb|Spina Bifida Meningocele has characteristic damage to the meninges of the spinal cord which are pushed out through an opening in the vertebrae as a cyst filled with CSF.]]
[[File:SpinaBifidaMyelomeningocele.jpg|right|300 px|thumb|Spina Bifida Myelomeningocele is the most severe form of spinabifida where the damaged spinal cord protrudes out with damaged meninges as a cyst filled with CSF.]]
[[File:SpinaBifidaOcculta1.jpg|right|300 px|thumb|Spina Bifida Occulta is the least severe as the spinal cord and meninges are undamaged.]]

'''Spina Bifida'''

In Australia, the risk of spina bifida is 1 in every 500 pregnancies. Spina bifida is a type of neural tube defect where vertebrae (which normally cover and protect the spinal cord) are not completely formed but are divided resulting in the defective spinal cord and its coverings to protrude through the opening (28,29).

There are three main types of Spina Bifida differentiated by their characteristic features:

1)Spina Bifida Meningocele characterized by normal spinal cord, divided outer vertebrae and meninges surrounding the spinal cord protruding from the divided vertebrae as a cyst (1,28).

2)Spina Bifida Myelomeningocele characterized by split outer vertebrae with spinal cord and its meninges protruding from the divided vertebrae as a cyst. Commonly found at lumbar vertebral level (1,28,29).

3)Spina Bifida Occulta characterized unfused vertebral arches and exposed vertebral canal. Spinal cord and its meninges still located in vertebral canal (1,28).

All forms of spina bifida are potentially fatal and in those where the spinal cord is damaged severe consequence arise including and paralysis and loss of sensation at and below the level of damage spinal cord damage (29,33). There is a lot of Spina bifida research using rabbit models to test the effective methods of correcting spina bifida. The occurrence of natural spina bifida in rabbits is rare and for experimental purposes it can be surgically created in rabbit fetuses during gestation (31,32). The process involves aesthetical sedation of the maternal rabbit at day 22 of gestation; a midline laparotomy performed and the desired type of spina bifida lesion created on the exposed fetus using forceps. Different methods for correcting spina bifida can then be tested and its effectiveness analysed (30,33,34).
[[File:Rabbitspinabifida1.jpg|center|350 px|thumb|Rabbit newborn with Spina Bifida. Note the unfused, divided vertebrae and exposed spinal cord.]]

'''Brachydactylia & Acheiropodia'''

[[File:Malformation1.jpg|right|150 px|thumb|Acheiropodia in rabbit characterized by amputations of the limbs and extremities.]]

[[File:Rabbitmalformation3.jpg|left|150 px|thumb|X-Ray study of rabbit limbs with malformed phalanges due to Brachydactylia.]]

Brachydactylia and Acheiropodia are genetic disorders characterized by skeletal malformation of the hands and feet (36,36). In Brachydactylia, the malformations commonly involve abnormal shortening of fingers and toes due to poorly formed or absent bones (35). Acheiropodia is characterized by more severe skeletal malformations including bilateral amputations of the distal upper and lower extremities as well as aplasia of the hands and feet. Although it is not fatal, the individual endures a very difficult life without hands and feet (37).

The inheritance mechanism of this diseases can has been studied through experiment using rabbits. Rabbits with abnormal genes coding for Brachydactylia and Acheiropodia are selected and bred to produce offspring with the disease (36). Brachydactylia and Acheiropodia are autosomal recessive disorders which means that two copies of an abnormal gene must be present in the affected individual in order for the disease to develop. Thus, each parent passes an abnormal gene to the offspring (35,36). The process of the malformation progresses from genotype to phenotype; small deletions on the chromosomes produce abnormal genes, the abnormal genes are then passed down to the offspring, the offspring that inherits two of the abnormal genes is unable to code for the correct proteins and as a result, there is failure in normal development of limb extremities in the embryo phenotype (37,38).

==Current Embryology Research==

There is currently great excitement in research involving rabbits in the fields of transgenesis, cloning and stem cells. We shall explore research in these areas by discovering some of the techniques used and how they have been applied to the rabbit model.

[[File:Trans1.jpg|right|170 px]]
[[File:Trans2.jpg|right|170 px]]
[[File:Trans3.jpg|right|170 px]]
[[File:Trans4.jpg|right|170 px]]
[[File:Trans5.jpg|right|170 px]]

'''Transgenic rabbit'''

A transgenic organism is one whose genome also contains genes from another species (39). The aim of creating a transgenic organism is to obtain a favorable characteristic in the organism’s phenotype (41). This desired characteristic of phenotype is obtained by altering the organism’s normal genotype to include the gene from another species with the desired characteristic (39,40).

The production of a transgenic organism involves several steps summarized below:

1) The chromosome and the desired gene on it are identified in an organism (39).

2) The gene is isolated from its DNA strand. This involves “cutting” it out of its DNA strand using enzymes called restriction endonucleases. The restriction endonucleases cut DNA at specific site so the desired gene can be removed from the DNA strand. The cut ends are known as “sticky ends” (39,40).

3) Separate DNA sequences for regulation sometimes have to be added to ensure the gene will work (40).

4) The gene is then inserted with a promoter sequence into the fertilized egg cell of a new organism producing recombinant DNA (39,44). To do this, firstly the new organism’s cell DNA must first be cut and the desired gene incorporated into it. The same enzymes are used to cut the new organism’s cell DNA because the DNA stands from the two different organisms will form matching sticky ends that will be attracted to and connect with each other in a process is called “annealing” (39,40,44).

5) DNA ligases are sealing enzymes found in all living organisms that help make and repair DNA (39,40). The DNA ligases are added to the annealed DNA fragments to help strengthen the bonds of the new recombinant DNA. The recombinant DNA is now transferred into the new organism’s fertilized egg by microinjection (44).

6) As the embryo develops and the recombinant genetic code read, new proteins are synthesized which code for the new desired phenotype characteristic in the transgenic organism (39,40).

Transgenic rabbits can be created in the laboratory by gene microinjection into the fertilized rabbit oocyte (44). In April 2000, a transgenic rabbit named Alba was born containing a gene from a Pacific Northwest jellyfish. The gene which was injected into a fertilized albino rabbit oocyte allows the rabbit to synthesize the green fluorescent protein (GFP) that is characteristic of the Pacific Northwest jellyfish. When illuminated correctly, Alba glows a bright green (43,46).

Transgenic rabbits have important research purposes. Transgenic rabbits can be created to model retinal degeneration (44). Retinal degeneration is a common problem with aging and diseases such as diabetes, and frequently leads to complete blindness (42). A genetic retinal degeneration disease called retinitis pigmentosa (RP) is created in these rabbits by introducing the “Pro347Leu” mutation of the rhodopsin gene into fertilized rabbit eggs (43,44). As the rabbit grows, it develops the disease which becomes progressively worse (45).
The use of these transgenic rabbits ultimately leads to better understanding of the disease and more effective treatments (42). [[File:Transgenic rabbit.jpg|center|250 px|thumb|"Alba" A trangenic rabbit with a gene from a Pacific Northwest jellyfish that allows it to synthesize the green fluorescent protein (GFP) of the jellyfish.]]

[[File:Crabbit 1.jpg|right|170 px]]
[[File:Rabbit2.jpg|right|170 px]]
[[File:Rabbit3.jpg|right|170 px]]
[[File:Crabbit 4.jpg|right|170 px]]

'''Cloning'''

Cloning is a method of producing genetically identical organisms. The principle of cloning relies on “tricking” an egg cell to begin rapidly dividing into an embryo (39). In the normal fertilization process, two haploid sex cells unite to form a diploid zygote which begins rapidly dividing into an embryo (40). By replacing the haploid egg cell nucleus with a diploid somatic cell nucleus, the egg cell is tricked into thinking it is fertilized and hence begins rapidly dividing to form an embryo (39,40,41).

The process of cloning involves several steps summarized as the following using a rabbit example:

1) A somatic cell is obtained from a rabbit and the nucleus removed (39).

2) An egg cell is obtained from a donor rabbit and the nucleus of the egg cell removed using an enucleation needle. The cell is now called an enucleated egg cell (egg cell without a nucleus) (39,41).

3) The nucleus of the somatic cell is inserted into the enucleated egg cell (41).

4) The cell is now stimulated to divide by applying pulses of electric current (39).

5) The rapidly dividing cell develops in culture for a few days forming the early embryo (40,41).

6) The embryo is then implanted into the uterus of another rabbit similar to the egg cell donor. This rabbit is called the surrogate mother (40,41).

7) The embryo develops and the surrogate mother gives birth to a rabbit fetus with near identical genotype of the somatic cell donor (the small genomic difference is caused by the fetus obtaining mitochondrial DNA from the egg cell donor) (39,41).

The cloning of rabbits has been achieved by inserting the diploid nucleus of a rabbit fibroblast (the principal cells in connective tissue) into an enucleated oocyte (49). There is currently much focus on the creation of controversial but revolutionary interspecies hybrid embryos where the nucleus from a human somatic cells are implanted into an enucleated egg cell of another animal (50). The resulting embryo (known as a chimera) will be almost completely human genotype but will have genome from the other animal (48). In 2003, scientists at the Shanghai Second Medical University fused human cell with rabbit eggs creating the first human-rabbit hybrid using the nucleus transfer technique. The hybrid embryo developed in culture for a few days before it was destroyed and the stem cells harvested (47,48). The purpose of the research into creating hybrid embryos is to provide researchers with human stem cells for experimentation into cures for diseases such as cystic fibrosis, Alzheimer’s and Motor Neuron disease as human stem cell are difficult to obtain (50).

[[File:Rabbit clone.jpg|center|450 px|thumb|(A) Cloned rabbits (5 month old) from nuclear transfer technique. (B) The male rabbit whose fibroblasts were used as the nuclear donors. The cloned rabbits have almost identical genome to the male donor.]]

'''Stem Cells'''
[[File:HES.jpg|right|200 px|thumb|Human Embryonic Stem cell (hES).]]
[[File:Rabbit knee.jpg|right|200 px|thumb|Stem cell induced cartilage repair of knee in rabbit.]]

Stem cells are unspecialized cells which are able to continuously reproduce themselves and under appropriate conditions, differentiate into all the various specialized cells of the organism such as cardiac cells, neurons and blood cells (39,40). Adults have a small number of stem cells when compared to a developing embryo and the stem cell of an embryo more easily obtained (41). Human embryonic stem cells (hES) derived from the inner mass of the preimplantation blastocyst have the potential to differentiate into all cell types in the human body and thus are valued by researchers (50). However, due to ethical and political issues, the obtaining and experimentation on human embryonic stem cells is difficult and alternate means are needed as stem cell provides potentially new treatments for a range of diseases (54).

Rabbits can be used both in the obtaining of stem cell for experimentation and also as recipients of stem cells to cure diseases. The human-rabbit hybrid embryo provides a method of obtaining stem cells for experimentation and these stem cells possess many similar properties to human stem cells, including expression of surface markers, special growth requirements, capabilities of self renewal, formation of embryonic body and differentiation into cells of all three germ layers (53).

Stem cell experimentation on rabbits also focuses on transplanting stem cell into rabbits to treat specific diseases. A study at Zhejiang University where a research team transplanted human mesenchymal stem cell into New Zealand white rabbits with myocardial infarction recoded regeneration of vascular structure and improvement in cardiac function. The research team noted the potential of stem cells in differentiating into specialized cardiac cells when subjected to the specific conditions of the rabbit heart (52).

Another study at Hallym University tested the effectiveness of transplanting mesenchymal stem cells from New Zealand white rabbits into damaged cartilage in the knees of other New Zealand white rabbits. In the experiment, mesenchymal stem cells were obtained from the rabbit bone marrow and injected into the knees of other rabbits that had cartilage in their knees surgically damaged. The research team were able to conclude notable cartilage recovery in the rabbits with the mesenchymal stem cell injection and the potential of mesenchymal stem cells to differentiate into fibroblasts, adipoblasts, osteoblasts and chondroblasts (51,53).

The findings in stem cell experimentation with in rabbits yielded positive results and potentially opens a new field of research in the use of stem cell to treat a range of diseases in humans.

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==Glossary==

Anesthetic - A drug that causes temporary loss of bodily sensations

Aplasia - The absence or defective development of a tissue or organ

Blastocyst - A stage of embryo development that occurs about five days after fertilisation when the embryo contains quite a few cells

Caudal - Situated towards the inferior or posterior end of the body

Cephalic - Relating to the head

Cerebral Aqueduct - A canal filled with cerebrospinal fluid within the midbrain

Cerebral Cortex - The layer of unmyelinated neurons (the grey matter) forming the cortex of the cerebrum of the brain

Cerebro Spinal Fluid (CSF) - A watery fluid which flows in the cavities within the brain and around the surface of the brain and spinal cord

Chromosome - Microscopic carriers of genetic material, composed of deoxyribonucleic acid (DNA) and proteins and appearing as rods under a microscope

Cisterna Magna - is one of three principal openings in the subarachnoid space between the arachnoid and pia mater layers of the meninges surrounding the brain

Diploid - A full set of genetic material, consisting of paired chromosomes one chromosome from each parental set

Dorsal - Position towards the back

Fontanel - Membranous gap between the bones of the cranium in an infant or fetus

Genome - All genetic information, the entire genetic complement and all of the hereditary material possessed by an organism. Made up of both chromosomal genome (inside the nucleus of the cell in the familiar form of chromosomes) and mitochondrial genome (outside the nucleus in the cytoplasm of the cell, usually in the form of one round chromosome (the mitochondrial chromosome))

Genotype - The genetic makeup of an organism

Glucocorticoids - A class of steroid hormones that bind to the glucocorticoid receptor (GR), which is present in almost every vertebrate

Haploid - A single set of chromosomes (half the full set of genetic material)

Laparotomy- Surgical incision into the abdominal wall; often done to examine abdominal organs

Ligases - Group of enzymes that catalyze the binding of two molecules

Oocyte - A female gametocyte that develops into an ovum after two meiotic divisions

Phenotype - The observable traits or characteristics of an organism, for example hair color, weight, or the presence or absence of a disease.

Pronuclear - Haploid nucleus before fusion of nuclei in fertilisation

Restriction Endonucleases - Enzymes that recognize and cleave specific DNA sequences, generating either blunt or single-stranded (sticky) ends

Retina - The thin layer of cells at the back of the eyeball where light is converted into neural signals sent to the brain

Rostral - Situated toward the oral and nasal region

Somite - Blocks of mesoderm on either side of the notochord and neural tube during development of the vertebrate embryo. Develop into muscles and vertebrae

Stenosis - Abnormal narrowing of a bodily canal or passageway

Weaning - Young become accustom to nourishment other than suckling

==Links to Research Laboratories and Researchers==

1) Transgenic lab: [http://www.dnavision.be/index.php]

Involved in development of transgenic organisms, DNA construction and phenotype analysis.

2) World Rabbit Science Association: (WRSA) [http://world-rabbit-science.com]

International Association where researchers exchange knowledge and encourage teaching, scientific research, practical experimentation, the collection and publication of statistics and documents relating to the rabbit. Even have their own journal called “World Rabbit Science”

Website provides contact with researchers, professors and veterinarians working with rabbits.

Example: Dr. Myriam Kaplan-Pasternak, Doctorate Veterinary Medicine, University of California, myriamsemail@gmail.com

3) American Veterinary Medical Association [http://www.avma.org]

The American Veterinary Medical Association (AVMA), established in 1863, is a not-for-profit association representing more than 78,000 veterinarians working in private and corporate practice, government, industry, academia, and uniformed services. Excellent website into animal research and has a range of veterinary journals.

{{Template:Projects09}}
[[Category:Rabbit]]
[[File:Example.jpg]]

Talk:2009 Group Project 1

2009-10-14T12:14:51Z

Z3185685: /* Actual Changes Made */

== Lab 10 ==
--[[User:Z3283499|Antonio Lee]] 10:52, 2 October 2009 (EST) Hi everyone, I will be working with you during the Lab10 Tutorial and here is the news link and PDF of the manuscript for your group exercise. I encourage you to read the paper before the tutorial. Also, please indicate next to the questions below (using either your initials or student number) which one of the four questions you wish to address.
:'''Group 1 :''' [http://www.nature.com/nature/journal/v461/n7262/full/461354a.html '''Developmental biology: Asexual healing'''] in Nature News and Views - Nature 461, 354-355 (17 September 2009) [[Media:ANAT2341_Lab10_2009_Group 1 Reading.pdf|Manuscript (PDF): Mitochondrial gene replacement in primate offspring and embryonic stem cells]]

:Question 1. What is the background to the existing problem / disease condition? --[[User:Z3187802|Vishnnu Shanmugam]] 22:12, 2 October 2009 (EST)

Mitochondria are found in all eukaryotic cells and contain their own genome (mitochondrial DNA or mtDNA). Unlike the nuclear genome, which is derived from both the egg and sperm at fertilization, the mtDNA in the embryo is derived almost exclusively from the egg; it is of maternal origin.

Mutations in mitochondrial DNA (mtDNA) can lead to a range of chronic incurable diseases such as myopathies, neurodegenerative diseases, diabetes, cancer and infertility. Mutations in mitochondrial DNA could also contribute to other diseases such as Alzheimer’s,
Parkinson’s and Huntington’s diseases

A normal cell should be homoplasmic in its mitochondrial DNA, that is it should only contain one type of mitochondrial DNA. But if the cell has two or more types of mitochondrial DNA (a mixture of normal and mutated DNA) it is known as heteroplasmic and can lead to a range of diseases. These genetic mutations can also be passed to offspring causing disease.
1 in 3,500–6,000 are at risk or presently have a disorder from mutations in mitochondrial DNA. Disease progresses slowly and there are no cure. Limitations in assessing the extent heteroplasmy and accuracy in calculating the risks of developing mtDNA related disease means that a new approach is needed to tackle the problem.

:Question 2. What approach / method did the research team take to tackle / improve the problem?--[[User:Z3126328|Jin Lee]] 12:31, 7 October 2009 (EST)
:Working with rhesus macaque monkeys, the authors reconstructed mature oocytes containing the nuclear genome from one oocyte and the mitochondrial genome from another. To do this they removed the nuclear genetic material from one oocyte, leaving behind all of the mitochondrial DNA, then transferred it to another oocyte whose nucleus had been removed (a cytoplast), but which contained a full complement of mitochondrial DNA.

:Question 3. What was the breakthrough / major advancement OR failure / drawback? and why might this be of significance?
::Drawbacks - --[[User:Z3186093|Jenny Guy]] 22:43, 7 October 2009 (EST)
:::There were difficulties in visualising and isolating the intact chromosomes, as well as the mtDNA being susceptible to damage and translocation/movement. Visualization became easier after the development of techniques for DNA staining with fluorophores and looking under UV light during embryo cloning by the SCNT (somatic cell nuclear transfer). Successful implementation to avoid damage to the cytoplast during spindle removal involved using polarized microscopy. (p368) --[[User:Z3186093|Jenny Guy]] 14:12, 8 October 2009 (EST)
:Question 4. What are the next steps in moving forward? What are the next or new hurdles to overcome?

==Actual Changes Made==

'''Concise Version:''' (Everyone add their changes here)
# Removed cleft palate and cleft lip section (Abnormal development) --[[User:Z3187802|Vishnnu Shanmugam]]
# Altered references (current research and abnormal development) --[[User:Z3187802|Vishnnu Shanmugam]]
# Added picture guide for transgenic rabbit --[[User:Z3187802|Vishnnu Shanmugam]]
# Added picture guide for rabbit cloning --[[User:Z3187802|Vishnnu Shanmugam]]
# Removed newspaper image of rabbit (Current research) --[[User:Z3187802|Vishnnu Shanmugam]]
# Formatted pictures and text to reduce gaps in the assignment (current research and abnormal development) --[[User:Z3187802|Vishnnu Shanmugam]]
# Corrected spelling mistakes in images (current research and abnormal development) --[[User:Z3187802|Vishnnu Shanmugam]]
# Reviewed all images and have written a summary, original source, copyright information (current research and abnormal development) --[[User:Z3187802|Vishnnu Shanmugam]]
# Formatted the look of the genetics section, including 'abnormalities' --[[User:Z3186093|Jenny Guy]] 16:31, 14 October 2009 (EST)
# Fiddled with position of images in genetics section --[[User:Z3186093|Jenny Guy]] 16:31, 14 October 2009 (EST)
# Fixed spelling mistake in History - Jin Lee
# Added images in table of stages. --[[User:Z3185685|Sumaiya Rahman]]
# Added to introduction and related it to the rest of the page. --[[User:Z3185685|Sumaiya Rahman]]

'''Long Version:'''

--[[User:Z3187802|Vishnnu Shanmugam]] 23:46, 10 October 2009 (EST) Okies, all done. I'm going to review all my images and add summaries to them. Dr. Hill asked for a concise version to all the changes we make from the peer review process. I suggest everyone add their changes to the list I have started above and place your signature next to it.

--[[User:Z3186093|Jenny Guy]] 14:29, 10 October 2009 (EST)Hey vishnuu, i was thinking could you please alter
* the gaps between the spina bifida images (format this somehow with the images on the side and text on the other)
* the gap under "Brachydactylia & Acheiropodia"...maybe you have entered down too much????
cheers :)

--[[User:Z3187802|Vishnnu Shanmugam]] 21:27, 9 October 2009 (EST)Hey all. I have removed the newspaper image of rabbit (Due to copyright issues), and have replaced it with a series of images that guides the reader through the process of cloning a rabbit. I have NOT altered the text summarizing the creation of transgenic and clone rabbits as there are very important & detailed information which if removed puts complex processes in danger of oversimplification. I also corrected spelling mistakes in some images.

--[[User:Z3187802|Vishnnu Shanmugam]] 20:22, 7 October 2009 (EST) Hey gang. By popular demand (or the stress of reading) people want less text. I have removed the entire cleft palate & cleft lip section from abnormal development. For current research, I have also created a step by step picture guide for transgenic rabbit creation. It was initially meant to be a video, but this wiki page does not display (.gif) or (.mov) files. Sum, I remember that you did your references after me...so when I removed the cleft palate & cleft lip section, the references changed....so I have also adjusted your references accordingly. I don't think it is necessary to make all the changes outlined below as most comments are subjective (different people have different preferences) and seems like some comments were made because people had nothing else to propose.

--[[User:Z3126328|Jin Lee]] 10:01, 8 October 2009 (EST)Hi Guys, I have fixed spelling mistake and some people commented to make table form for advantages and disvantages section. But I liked the way I presented so I will leave in point form.

--[[User:Z3186093|Jenny Guy]] 14:32, 8 October 2009 (EST)
Hey! I looked at what i could change in the genetics section and decided to format a little. Our peers asked:
* genome information into a table - this is a little silly since there'd only be one column.
* Reformating in sections such as hitory and genetics. - have tried to do a little.
* Make pictures appear on the same side of page. maybe aligning the pics on either the left or right side instead of both left and right, and possibly putting them as thumbnails could also work. - i tried to put both of the chromosome images ont he same side (tried both left and right) but found that it looked terrible considering the size (which is needed to see it) as the text wouldnt fit around it very well.
* it will look much better if there is some work to be done for the structure of it especially the paragraph under the heading of 'abnormalities'. - am still in the process. not sure what else i can do since its in basic dot point form with not a large text to format. any ideas? or shall i leave it how it is now?
* maybe instead of writing the entire reference, you could just state The Broad Institute or just the people related to it - i feel that the entire team needs a mention since all people relate to it. noting just the broad institute is almost like noting a team of people here in unsw as just plainly "UNSW" which is just disrespectful.

==Things to work on noted by peers==

Hey, So the changes i will make will be in the introduction section. Also a lot of people have said to add pictures in the stages section to make it more interesting. I couldnt get permission to use the images so i bought tracing paper today! lol will try to draw them and see if they are ok enough to add. I think i am going to leave the timeline section as is because most people liked it. What do u guys think? --[[User:Z3185685|Sumaiya Rahman]] 15:31, 8 October 2009 (EST)

Sounds great Sum....Its gonna take some effort to trace it then scan it. GL --[[User:Z3187802|Vishnnu Shanmugam]] 21:37, 9 October 2009 (EST)

Hey guys,
I read through all the notes our peers have given us and summarised them into the following sections. Majority of them overlap (where ive put a new persons opinions in the same dot point over and over to stress the point on how many people noticed). Some things are easily changed, most of all i reckon its
# formatting
# pictures
# text to be more concise
So we just need to finalise all these minor things to improve our project. Please detail any changes you've made in the the heading above.
Cheers, --[[User:Z3186093|Jenny Guy]] 20:30, 7 October 2009 (EST)

INTRODUCTION
* a little too brief, more information needed
* For the first sentence (the characteristics that make the rabbit an excellent model for study), mention the section 'Why are we using rabbits?' under History section.
* For the second sentence (study that developed and improved micromanipulation techniques), mention the 'Transgenic Rabbit' section below under the genetics section. I've read the entire project page, and the introduction was the only place I found that was not precise enough (which is a great thing). These are minor things, but I think they will help with improving your project page.
*suggestion: Place the history section after the Introduction. This gives the viewer an overview of the use of the rabbit embryo. This way the viewer is first subjected to a few examples of the rabbit embryos use. It also allows him/her to understand where the rabbit embryo sits in with history. I guess this is a matter of personal preference.

HISTORY
* The advantages and Disadvantages would be better in a table. the history you might want to put the advantages and disadvantages into a table to make the page look a bit more tidy and easier to read when we go through it.
* The usage of rabbits for experimental models in science and medicine could be stated under the history section to allow background information for the readers to become aware of the topic and why the rabbit have been used to study specfic medical procedures and diseases.
* Spelling mistake under 'Discovery of Graafian Follicle', 2nd paragraph. I think it's previous instead of 'previcous'.
* Reformating in sections such as hitory and genetics. Make pictures appear on the same side of page.
* The history section can be improved if the infomation is expanded to give some more detailed background knowledge although i like the idea that the information is concise describing each scientists contribution towards the model.
* could be formatted to make the information stand out and a lot more appealing, I would recommend including pictures if possible that link to the text and making the advantages and disadvantages into a table rather than listing it.

TIMELINE
* more images to wholly understand. timeline/staging section was clear and concise, however it could be improved by adding more colour/pictures to maintain the readers' interest. The timeline and staging bits are very well written and clear but i think you should add a few images in there to match up with the text. Perhaps some pictures of embryos throughout development. Pictures for every stage would make it more visually attractive rather than just reading text. lack of pics in the timeline.
* It’s a little confusing that the development jumps back and forth according to the body part developing. Maybe it should be categorised according to time of development instead for greater clarity at first glance
* The timeline is just a little confusing, as its divided into development of different parts, which breaks the time flow.
* some of the information for the timeline section was too heavy for the page - would recommend only using some of the information on your actual page and having the rest as links to separate pages

STAGING
* pictures for stages would have been nice, unless there were none????
* a more even distribution of information, particularly more detail in the stages
* Provide pictures for individual stages. Get visual, and make the stages interesting to read. include pictures in the stages section.
* Staging section is also very well presented but the information presented in a table would even look better if there is use of some pictures to make it more interesting for its audience.
* staging section was very bland and would be more appealing with pictures. I dont think its necessary to cite your entire reference within the text

GENETICS
* genome information into a table
* Reformating in sections such as hitory and genetics.
* Make pictures appear on the same side of page. maybe aligning the pics on either the left or right side instead of both left and right, and possibly putting them as thumbnails could also work.
* it will look much better if there is some work to be done for the structure of it especially the paragraph under the heading of 'abnormalities'.
* maybe instead of writing the entire reference, you could just state The Broad Institute or just the people related to it

ABNORMAL DEVELOPMENT
* There is also a lot of content which might be alleviated by reducing the section on abnormal development. Too much information about the abnormalities. make more concise.
* the abnormalities went a bit over board, and didn't need that much attention I think (as compared witht the research which was good)
* reduce the writing content. for example. In the current research section, you have two scientific process of transgenic rabbits as well as cloning which is described in how these are done. why not draw a step by step diagram, and put these written steps in the link to the image.
* The information provided under Hydrocephalus and Brachydactylia was informative and interesting, but it contained too much text. I suggest you narrow it down and make use of Dots point, numbering, bold/italic words, and/or sub-sub-headings.
* Section for "Abnormal Development" gives the readers useful amount of information but i think its very lenghty, use of dot points can make it look even better and easy to understand.

CURRENT RESEARCH
* the group makes good usage of diagrams but towards the end diagrams die out, you might want to make the current research part of your assignment into diagrams and steps as there is just a bunch of information thrown there and alot of reading needed, if you put it into steps or diagrams it will make the marking process and reading process easier and allow us as reader to understand the information with ease.
* 'Transgenic Rabbit' should be shifted toward the genetic information on the rabbit. (Jenny - i dont agree with this as its research, not its offical genetics. Vishnnu - Neither do I)
* information in regard to stem cells should be brief and truncated. Example in regard to stem cell research should have brief and simple model explaining the process and why it used.
* There is too much information under stem cells. There is 2 examples of studies dealing with stem cells. A suggestion would be to just have one, and have a link saying 'Koga's research on Stem Cells'.
* Have the section 'links to Research labs and researchers' placed at the end of current research. That way, the information on the page will flow smoother.
* more of a focus on current research i.e. what each method is being used for and less on the process behind each method.
* great amount of information but in my perspective replacing the paragraphs with some dot points with heading and subheadings would further enrich understanding of readers.

OVERALL
* "As you start going down the page though the information starts to read a bit haphazardly, for example the developing body; jumping for section to section and the timeline section. it would be great if you could clean this up as it doesn't really flow." - formatting
* condense long slabs of text as the page is long
* format it so there are no huge gaps
* move the links to current research labs up closer to the current research section, just to keep it all together

==Constructive Criticism of Coordinator==
--[[User:S8600021|Mark Hill]] 08:07, 8 October 2009 (EST) The following comments are general in nature in no specific order, as it would be inappropriate to suggest specific changes and then assess the final project. Comments will be added during this week and you still have one week before final submission.

* There is no concise list of changes made to your project on the basis of peer assessments.
* Timeline of Embryo Development early stages, are in the introductory text said to be in hours, but it would be good to see it in the list as well.
* [[:File:Sizes.JPG]] Relative sizes, but no absolute size or scale given.
* A general comment about images. When you click an image and it opens, the information below the image should have an explanation of what the image shows, a reference (if from a paper) and a link to the original source (if available) as well as copyright information.
* Did you actually read the terms of use for this image that you cut n pated into the image description? [[:File:Rabbit_hybrid.jpg]] "For this purpose alone you may retrieve and display the Content on a computer screen. You may also print out, but not photocopy, one copy of individual files on paper and store files in electronic form on disc, but not on any server or any other storage device connected to a network where the Content could be accessed by other users." It clearly states that you cannot use this image online.
* Chromosomes section, images have no legends and structure not clearly organised.
* There needs to be better checking of your spelling and grammar, for example [[:File:Rabbitmalformation3.jpg]] "Plant Patkology of Tke Rockefeller Institute for Medical Researck", these mistakes while not major, suggests a lack of reviewing of your work by the group.
* Just a comment on project "feel", when several people work together on a project and insert their parts, the final project sometimes has an uneven style. Now that you have time to tidy up, try and get a common appearance throughout your project.

==Constructive Criticism of Peers==

--[[User:Z3218657|Sally Clarke]] 09:32, 1 October 2009 (EST)
Nice work Guys!
- Fantastic images used throughout - maybe a few more in the timeline so we can understand what is going on
- As you start going down the page though the information starts to read a bit haphazardly, for example the developing body; jumping for section to section and the timeline section. it would be great if you could clean this up as it doesn't really flow.
- The section on the abnormal development is great.
- The page is quite long - Maybe you could condense some of the text as it is kind of slab like
- i really enjoyed the breeding section
- The advantages and Disadvantages would be better in a table.

--[[User:Z3223194|Bronwyn Lewis-Jones]] 08:08, 1 October 2009 (EST) Hi Group 1! This is obviously a well organised and well researched assignment. I found it very informative. There are (of course) some things I feel could improve the overall submission. I loved that the timeline/staging section was clear and concise, however I think it could be improved by adding more colour/pictures to maintain the readers' interest. There is also a lot of content which might be alleviated by reducing the section on abnormal development. Hope this helps :)

--[[User:Z3218146|Julianna Lam]] 01:11, 1 October 2009 (EST) good job guys.
-Theres alot of relevant information.
-The timeline and staging bits are very well written and clear but i think you should add a few images in there to match up with the text.
-The image for the genetics bit is awesome.
-The page is nicely set out.
-Too much information about the abnormalities.

--[[User:Z3258567|Sando Rashed]] 20:04, 30 September 2009 (EST)hey guys, your page looks good, starts off well as there is not a bunch of information just thrown in, the information used is well thought, with the history you might want to put the advantages and disadvantages into a table to make the page look a bit more tidy and easier to read when we go through it (you can also do this with the info under genome), the group makes good usage of diagrams but towards the end diagrams die out, you might want to make the current research part of your assignment into diagrams and steps as there is just a bunch of information thrown there and alot of reading needed, if you put it into steps or diagrams it will make the marking process and reading process easier and allow us as reader to understand the information with ease, other than that the page looks quite good, well done on all your contributions

--[[User:Z3218792|Gabriela Pinget]] 21:51, 29 September 2009 (EST)

Nice page. I particularly liked the idea of lists of what is to come before each flood of information as was done with the ‘history of model use’ section.

- Nice easing into the topic with ‘advantages’ and ‘disadvantages’ lists.

- I liked the of rabbit embryo development to that of humans- puts it into perspective

- Good glossary- informative but not over- the- top

- Nice genetics section! Easy to read and a great use of illustrations to break up the information

- I also like that you took a page out of Mark’s book in the addition of the abnormalities section

Improvements:

- Perhaps some pictures of embryos throughout development.

- It’s a little confusing that the development jumps back and forth according to the body part developing. Maybe it should be categorised according to time of development instead for greater clarity at first glance

--[[User:Z3295026|Joe Nassif]] 17:01, 29 September 2009 (EST)

Your assessment has come along great in regard to the criteria format. There are a few alterations that could improve your project, the following alterations may enhance your wiki page:

'''-''' The usage of rabbits for experimental models in both science and medicine could be state under the history section to allow background information for the readers to become aware of the topic and why the rabbit have been used to study specfic medical procedures and diseases.

'''-''' Secondly the information on 'Transgenic Rabbit' should be shifted toward the genetic information on the rabbit. So far the project is looking and coming along great except for minor edits.

'''-''' Background information should be placed subsequent to the introduction allowing the reader to understand why this specific animal is used for specfic purposes.

'''-''' Figures/Graphs and the illustration of the anatomy and genetic development of the embryo were useful and clear allowing the viwers to understand and learn through the demonstration of pictures which were extremely informative.

'''-''' Genetics: the Genetics and Abnormalities information was great and very informative. It was great how the group compared the embryo with the human chromosome allowing the audience to understand the difference between both.

'''-''' Abnormalities: Information and details which were in the genetic section provided informative and interesting information, and it could be truncated a bit, additionally just discussing the chromosome development of the rabbit.

'''-''' Current Embryology Research: information in regard to stem cells should be brief and truncated. Example in regard to stem cell research should have brief and simple model explaining the process and why it used.

'''-''' Consequently, I thought the project was good it flowed and was very informative. The information was detailed, and the illustrations were useful and allowed the readers to gain a brief overview on the topic and it usage in history and in current research. Overall group 1 seem to achieve the critriea outcomes and summarised the topic really well, the comparsion to human embryo development througout the text was great and is a good referencing point in comparsion to the species choosen.
Great job --[[User:Z3295026|Joe Nassif]] 17:01, 29 September 2009 (EST)

--[[User:Z3255007|Sadaf Masood]] 12:09, 30 September 2009 (EST)Hello Group 1! Congrats on your awesome group project! I must say im very impressed with all the information you have posted and i have listed down the good bits and the bits that need to be improved. Since i am posting this a lil late, i have seen that u have already improved your project and few aspects...Good Job guys!

1. Very brief introduction...maybe just a little bit more info will be perfect

2. Abnormalities section is very informative and well researched, but very long, how about making it a little more precise?

3. The Advantages and Disadvantages of the using Rabbit is just simply perfect

4. The timeline is just a little confusing, as its divided into development of different parts, which breaks the time flow.

5. Pictures for every stage would make it more visually attractive rather than just reading text

6. Great Glossary!

There were few things earlier that need to be improved but you guys fixed it as soon as comments were posted so basically you guys rock :)An excellent effort guys. Best Wishes

# --[[User:Z3217015|Mitchell Mathieson]] 09:45, 25 September 2009 (EST)Very nice. The information was maybe a bit spread out, with heaps of gaps everywhere (formatting???), but the information was there, and relevant, and easy to read. I like how there was tonnes of information on current research, as I think that was the main aim, but the abnormalities went a bit over board, and didn't need that much attention I think. pictures for stages would have been nice, unless there were none???? The references are top notch, and the glossary is pretty amazing, and in the right place. Overall very good, I think formatting was the major downfall though, as it makes the page that much longer, and hence a little bit more difficult to read.

--[[User:Z3224449|Elide Newton]] 14:12, 26 September 2009 (EST)
HEllO GROUP 1: Well done on such a great assignemnt, looks like you have all worked very hard. Well my one point of constructive criticism would be to reduce the writing content. for example. In the current research section, you have two scientific process of transgenic rabbits as well as cloning which is described in how these are done. why not draw a step by step diagram, and put these written steps in the link to the image. that way it is more visual, the info is still there under the image link, and the page wont look as daunting to read. :) hope this helps!

--[[User:Z3254857|Begum Sonmez]] 00:46, 26 September 2009 (EST)
Hello Group 1. Firstly, I would like to let you all know that you have all done a great job. I'm impressed. I have a few suggestions that I think mite help to improve the page even more:

*Introduction:

1)For the first sentence (the characteristics that make the rabbit an excellent model for study), mention the section 'Why are we using rabbits?' under History section.

2)For the second sentence (study that developed and improved micromanipulation techniques), mention the 'Transgenic Rabbit' section below under the genetics section. I've read the entire project page, and the introduction was the only place I found that was not precise enough (which is a great thing). These are minor things, but I think they will help with improving your project page.

3)Breeding information was informative.

4) A suggestion: Place the history section after the Introduction. This gives the viewer an overview of the use of the rabbit embryo. This way the viewer is first subjected to a few examples of the rabbit embryos use. It also allows him/her to understand where the rabbit embryo sits in with history. I guess this is a matter of personal preference.

*Timeline:

1)Graphs, and the illustration of the zona pellucida and mucin coat were very clear and informative.

*Staging: I had no problems with it. The lack of information I think was a plus. It touched on the content in the Timeline section.

*History:

1) I loved the idea of the 'Disadvantages' of the rabbit embryo, it seemed unbiased. The brief timeline provided a clear and short summary.

2) Spelling mistake under 'Discovery of Graafian Follicle', 2nd paragraph. I think it's previous instead of 'previcous'. Also, the 2nd paragraph under this heading does not flow that well. Try rephrasing the 2nd sentence.

*Genetics:

The Genetics and Abnormalities section flow into eachother very well. I appreciated the comparison of the rabbit chromosome to the human chromosome.

*Abnormalities:

1) The information provided under Hydrocephalus and Brachydactylia was informative and interesting, but it contained too much text. I suggest you narrow it down and make use of Dots point, numbering, bold/italic words, and/or sub-sub-headings.

*Current Embryology Research:
1) There is too much information under stem cells. There is 2 examples of studies dealing with stem cells. A suggestion would be to just have one, and have a link saying 'Koga's research on Stem Cells'.

2) Have the section 'links to Research labs and researchers' placed at the end of current research. That way, the information on the page will flow smoother.

Overall, I thought there was a consistent structure in each section. The information was informative, and the pictures were relevant and helped me better understand the topics of discussion.

--[[User:Z3252340|Emily Wong]] 10:58, 27 September 2009 (EST) Firstly, great work. It is a well researched, structured and organised page. The content is very in depth and includes information on all of the specified areas. It is well referenced, with an extensive reference list indicating the amount of research put into the page. Some areas are more detailed than others. For example, the staging section is quite short and concise where as the Abnormal development section is extremely long considering it is not a needed topic. There is moderate use of pictures and diagrams, but more use could benefit the page as it may be able to negate some of the large slabs of text. The comparisons made between the human and the rabbit embryos are a good part of the project page. Each member of the group has contributed to the page and provided a lot of information on the section of content they were working on. What would improve this project is a more even distribution of information, particularly more detail in the stages, a few more diagrams or pictures to negate some of the text presented, more of a focus on current research i.e. what each method is being used for and less on the process behind each method.

--[[User:Z3126345|Gang Liu]] 14:26, 27 September 2009 (EST)In my opionion, this is a well constructed page. It includes major subheadings such as history, timeline, stages, genetics and current research. It is very concise and straightforward, which makes it easy to read. For example, a short introduction paragraph,"...the rabbit is an appropriate animal model as the results from many experiments are significant to that of other mammals, including humans.", explains to reader why rabbit is such a suitable model.

It also provides a logic flow. For example, in history of rabbit model use section, it has provided advangtages and disadvantages of model use. This is appropriate, as it demonstrates the significance of rabbit model use in scitific discovery. In addition, it has provided detailed background information for each discovery. This makes it interesting to read.

It is also important to compare development of embryo between rabbit and human. For example, "... the similarities of this developmental pattern in humans and rabbits, suggests that the same growth increment is required to achieve the same stage. The main difference observed between human rabbit gestational duration is due to the fetal growth phase...", this has suggested human and rabbit share many similarities. Not only this page has demonstrated detailed written information of timeline development, it also provided graphics to reinforce the concept. For example, the hand drawing of developing embryo. As well as the comparison between human embryo and rabbit embryo timeline development.

It is also interesting to learn that rabbits have 22 pairs of chromosome, whereas humans have 23 pairs of chromosome.

Sections such as abnormal development and current research have demonstrated extended research and understanding. For example, hydrocephalus, spina Bifida, stem cell research and cloning techniques. All of these have showed the in depth research in textbooks, journals and internet based literatures.

However, this page can be improved by considering the following points.

*Provide pictures for individual stages. Get visual, and make the stages interesting to read.

*Reformating in sections such as hitory and genetics. Make pictures appear on the same side of page.

*Typo: "A rabbits potential for reproduction..."

*Sections such as abnormal development and current research are too lengthy. Might consider shrink the content.

*Lack of glossary.

Overall, big thumbs up!

--[[User:Z3252231|Angama Yaquobi]] 01:12, 28 September 2009 (EST)
First of all i would like to congratulate all the team members for a great team work.
Well done guys!! The group project looks amazing, the information presented is very concise
and straight to the point which makes it very easy for the readers to grab
the important information that they need to enhance their knowledge.
I like the section of history, the information is very clear,
and i like the idea of providing some background knowledge to the readers
about the disadvantages of the use of rabbit.
The history section can be improved if the infomation is expanded
to give some more detailed background knowledge althought
i like the idea that the information is concise describing each
scientists contribution towards the model.
The section for timeline is impressive, in my perspective its a great idea to cover alot of content in a very smart way
which is by the use of subheadings to make it easy to understand for audience.
Staging section is also very well presented but the information presented
in a table would even look better if there is use of some pictures
to make it more interesting for its audience. Genetics section
is beautifully presented, all the information is there with some
amazing pictures but will look much better if there is some work to
be done for the structure of it especially the paragraph under the
heading of 'abnormalities'. Section for "Abnormal Development" gives
the readers useful amount of information but i think its very lenghty,
use of dot points can make it look even better and easy to understand.
The same for Current embryology research, great amount of information but
in my perspective replacing the paragraphs with some dot points with
heading and subheadings would further enrich understanding of readers.
Also glossary would complement the webpage. But overall,
great amount of information which shows alot of research
which has been done by all the team members. Well done guys!!

--[[User:Z3217686|Thomas Dangerfield]] 13:29, 28 September 2009 (EST) Hey guys! Good work on your assignment! Plenty of info which is good, and very well referenced. The glossary is a good idea too! I do agree with a few others about the lots of clear spaces in the formatting, and the lack of pics in the timeline though. Also under the genetics section, maybe aligning the pics on either the left or right side instead of both left and right, and possibly putting them as thumbnails could also work. In the abnormalities section, there might have been a little too much info that probably wasn't needed, but i do like the effort put in. Over all, possibly more time spent on formatting and determining which sections are more important and which sections may need to be limited. Other than those points, the whole assignment seemed very well done!

--[[User:Z3215682|Carly Mooney]] 11:32, 29 September 2009 (EST)
You assignment is visually appealing and the genetic information e.g. the number of chromosomes of a rabbit was very interesting.There are some additional sections you have added which really complement your assignment e.g the abnormalities and I really liked the advantages and disadvantages of using the rabbit model. The few suggestions I would make is to:
* include pictures in the stages section
*place the pictures throughout the text (e.g. to left or right). You did this up until abnormalities and I felt it broke the flow of the written text.
* and maybe move the links to current research labs up closer to the current research section, just to keep it all together.
Overall very impressive though.

--[[User:Z3220040|Joanne Raffel]] 15:25, 29 September 2009 (EST) Nice wikipage, the page looked interesting however I agree with some others that the formatting of the page was inconsistent. I thought the referencing was great but found it a bit confusing with the reference numbers after the paragraphs. I thought the subheadings werent distinct enough, especially in relation to the text, which made it difficult to read. The history section could be formatted to make the information stand out and a lot more appealing, I would recommend including pictures if possible that link to the text and making the advantages and disadvantages into a table rather than listing it. I especially liked the comparison between the rabbit and the human embryo, however some of the information for the timeline section was too heavy for the page, I would recommend only using some of the information on your actual page and having the rest as links to separate pages. The staging section was very bland and would be more appealing with pictures. I dont think its necessary to cite your entire reference within the text, especially in the genetics section, maybe instead of writing the entire reference, you could just state The Broad Institute or just the people related to it. The abnormalities section was a good inclusion however it was very extensive, along with the current research section. Overall a very good wikipage.

----
*Hey, Well done guys!!! I think our group worked pretty well! I think we communicated each other well and did very best for their section. I fixed my spelling mistake and problem with sentence! As Begum mentioned, I think placing the history part after the introduction is better idea. --[[User:Z3126328|Jin Lee]] 13:36, 26 September 2009 (EST)

*Hey guys,
the project has come together brilliantly! it looks quite good. Hopefully mark will like it! ill add some terms to the glossary and try do some formatting (the first image is a little too big i think!) --[[User:Z3186093|Jenny Guy]] 10:28, 24 September 2009 (EST)

Hey. Yep all good. I had to get rid of the pics, so stages table is now blank. Im pretty much done. I'll see what i can add to the glossary. thanks :)--[[User:Z3185685|Sumaiya Rahman]] 23:34, 23 September 2009 (EST)

Hey all, I'm going to start a glossary and add it under the reference section. Scan your text and add to the glossary in alphabetical order. Also under the marking criteria, it says to provide links to researchers and research laboratories.....i'll start that under the glossary. Everyone else OK with their stuff?--[[User:Z3187802|Vishnnu Shanmugam]] 23:08, 23 September 2009 (EST)

Hey Sum, The images look fine but I don't think you can use the images like that since the journal KARGER is being particular about its copyright laws. I tried tracing around the images but it does not seem to resemble anything like an embryo. I did however find this link...go to it and scroll down to the images of the developing embryo. You might be able to edit it to resemble rabbit embryo. --[[User:Z3187802|Vishnnu Shanmugam]] 15:10, 23 September 2009 (EST). To get to the link, Google image search "rabbit gestation"....click on the "rabbit,gestation age" image from nature.com
Also google image search "The Haeckel embryo sequence"...could be useful after some editing

oh my god!! I summarised all of my research and wrote down on the page. Then I blew up everything!!!
it says 'edit conflict' what da?? I lost all of my work...it was my stupid mistake...--[[User:Z3126328|Jin Lee]] 01:06, 23 September 2009 (EST)

Oh also.. let me know if the images look stupid --[[User:Z3185685|Sumaiya Rahman]] 00:34, 23 September 2009 (EST)

Hey thanks vishnuu. I put some images up in the stages table. I did edit the pictures, but im not sure if im allowed to use it like this? have a look and let me know. Also im not sure what is going on with the reference section seems kinda all over the place, so i havnt added mine in yet. Maybe we should fix that up somehow? :) oh LOL about the breeding rabbits bit! haha
--[[User:Z3185685|Sumaiya Rahman]] 00:31, 23 September 2009 (EST)

Hey Sum, Sorry for the late reply. For $330, I'd rather breed rabbits and take the photos myself. I had a look at the original images, what we can do is trace around the developing rabbit embryo using the pencil tool on an image editing software(eg. microsoft paint - already preloaded into most windows). Then upload the image to the assignment. Does your PC have adobe fireworks?...extremely good for tracing images. If not, have a go at it with microsoft paint....I shall also have a go at it, then I shall let you know on this discussion page at about 3PM t'morrow. If any good then I'll send it to your student email. If not, we discuss potential alternatives. good luck Sum! --[[User:Z3187802|Vishnnu Shanmugam]] 23:51, 22 September 2009 (EST)

Yep thats the article i used for the developmental stages and put in a table. I should have my timeline posted by end of today. I also couldn't get permission to use the pictures as they wanted about $330 for me to use it!! no thanks. I'll see if i can work it in somehow. Vishnuu did u have any ideas on editing the images?? --[[User:Z3185685|Sumaiya Rahman]] 12:29, 22 September 2009 (EST)

Have a look at this article, it's helpful for comparison bt rabbit and human in developmental stages!--[[User:Z3126328|Jin Lee]] 13:35, 21 September 2009 (EST)
*Sampled rabbit embryos were staged using the Carnegie criteria, in order first to determine if they were consistent with the rabbit developmental pattern, and second to compare this pattern with the human one. Our results show a suitable '''comparison of rabbits and humans in early developmental stages''', except for the neural growth.
[http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowAbstract&ArtikelNr=73136&Ausgabe=229537&ProduktNr=224239
]

Absolutely correct Juliana, my research articles and their links are labelled 1-6 so far, the rest is yours..... I'll fix it for you. A timeline image seems tricky and i'm unsure, send Dr. Hill an email on m.hill@unsw.edu.au and see what he says. We still have till thursday to finish everything, so don't be too worried....try to finish all your other stuff and leave the drawing of the timeline last.--[[User:Z3187802|Vishnnu Shanmugam]] 17:49, 20 September 2009 (EST)

*no.1-7 in reference section is mine. and I think links under Vishnnu's research on the discussion board is mine. let me know please. (I can't remember all of my researches)
I want to make a timeline image but I can't do it;;; I asked Mark few weeks ago but havn't replied yet....can somebody help me???--[[User:Z3126328|Jin Lee]] 17:26, 20 September 2009 (EST)

'''** Hey Jenny, dont worry!! the project is not due until next week! (24th) we will have it done by then!! I am still waiting for permission to use the pictures in my stages section, thats why it hasnt been done yet. Hopefully i can get permission, otherwise i'll have to draw them (or something) myself.''' --[[User:Z3185685|Sumaiya Rahman]] 14:03, 17 September 2009 (EST)

It says project due date 24th september.......if the due date had been brought forward why was it not posted on the project main page? --[[User:Z3187802|Vishnnu Shanmugam]] 13:48, 17 September 2009 (EST)

EVERYONE...WHY IS THE REST OF OUR PROJECT NOT DONE??
* vishnuu...its due TODAY!! how can you post things up next Monday? Please make sure youve referenced EVERY image and all text (i know youve said you need to do this...but its easiest done when writing the section as now you have to go back and find everything, insert numbers etc. Remember to put the reference in the reference section. For the current research section i thought this might help you (as during my lecture in another class they spoke about how rabbits are used in heart development. Is there anything that you've found to include this?). Also I found this website during my research so it may help you? [http://www.evergen.com/rabbit_experience.html/ Rabbit Experiments]
* sum - where is the timeline???? It doesn't exist? Where is it? Also, we need some sort of visual for the staging. Have you found an images? Could you draw the stages of embryo development? It just looks incredibly boring.
* julianna...you need to put up more other than just two historians...there is NO referencing whatsoever in your entire section. where have you found this information? have you put it in your own words or copied it? You need to add some more refences to the reference section at the bottom..there just aren't many to back up your research.

seriously guys. ive added photos and tried to spice up the project but i am NOT going to finish your sections for you. ITS DUE IN 3 HRS! i cant believe you guys haven't bothered to even try finish this. Im very disappointed and i think its slack to let the team down. --[[User:Z3186093|Jenny Guy]] 10:34, 17 September 2009 (EST)

----

Hey all, just need to finish editing the current research part before i post it up, also need to edit some of my images under abnormal development and also references. Should be all done by Monday. --[[User:Z3187802|Vishnnu Shanmugam]] 07:02, 17 September 2009 (EST)

--[[User:S8600021|Mark Hill]] 01:40, 8 September 2009 (EST) OK guys, this is still just a page of text......

--[[User:Z3126328|Jin Lee]] 14:50, 3 September 2009 (EST) I want to make a timeline?

--[[User:S8600021|Mark Hill]] 08:42, 21 August 2009 (EST) z3187802 has contacted me and has been away sick. He should still complete his components of the group project.

Our group is Sum, Vishnnu, Juliana and Jenny. Today in the lab we have decided to research the RABBIT! [http://embryology.med.unsw.edu.au/OtherEmb/Rabbit.htm/ Rabbit embryology from Mark Hill]

(Juliana's email belebele85@msn.com)

----
This is apparently what we need to include in our case study:
#Timeline of Embryo Development - how long (SUM)
#Staging - are there species specific staging, what occurs when (SUM)
#History of Model Use - when was it first used, (JULIANNA)
#Genetics - chromosome number, sequencing (JENNY)
#Abnormal Development (VISHNNU)
#Current Embryology Research - research papers and findings (VISHNNU)

Hey guys, maybe we should add a section comparing rabbit to human development
--[[User:Z3185685|Sumaiya Rahman]] 16:45, 6 August 2009 (EST)

That sounds like a good idea Sum....seeing that human development is the primary theme of the course, not including it would be criminal!. -vishnnu

Report:
* Links to resources and discussions are to be posted on the group talk page, the project page is for the actual assignment
* Final assignment will be marked by another group and everyone will be given a marking criteria
* No information should be obtained from Wikipedia and all information (tables & graphs included) must be referenced
* Please feel free to suggest any further topics which can be included

== Research: ==
So i think the main rabbit used in research is the oryctolagus cuniculus. Lets focus mostly on that (or at least i, Jenny, will since im going genetics). This link is great for the specific genetics: [http://www.ncbi.nlm.nih.gov/nuccore/AJ001588/ Oryctolagus cuniculus complete mitochondrial genome]

Here's some stuff about benefits of modeling from a textbook. I haven't yet written as my own so its still the authors material. Just thought it might benefit us all (and raise our morale as we thought the rabbit might suck..but it doesn't!) We're not "submitting" this as our own work so technically we're not yet copyrighting their material.
Ive cited the book here and the website i got it from:
[http://books.google.com.au/books?id=RY0rXE2HgqsC&pg=PA344&lpg=PA344&dq=rabbit+embryology+genetics&source=bl&ots=rbr3CuBRxY&sig=p8055w9oYQmsQeuN78mgXBGmRK4&hl=en&ei=NI2KStaQJIvSsQOEpMjEDQ&sa=X&oi=book_result&ct=result&resnum=3#v=onepage&q=&f=false/ Cibelli, J., Lanza, R., Campbell, K. and West, M. 2002. Principles of Cloning. Academic Press]

“Rabbits were one of the first species in which blastomere nuclear transfer succeeded; as a model species, rabbits placed a central role in developing the micromanipulation technologies in embryos.” Other advantages for using rabbits are:

# “The costs to animal procurement, animal care, and oocyte production in rabbits are relatively low compared to large animals.” e.g. a cow embryo is 30x more expensive that a rabbit embryo
# “The developmental biology of rabbit embryos and fetuses resembles more closely that of large farm animals than that of rodent model species, including the transition from maternal to embryonic control of embryo development.”
# “The pregnancy of rabbits is relatively short (1 month), allowing rapid evaluation of fetal and postnatal development. In comparison, the gestation length for cattle is 9x longer.”
# “The sizeable milk production of rabbits allows their use as test animals for therapeutic protein expression in milk, or as a living bioreactor.”
# “Rabbits are induced ovulators. Domesticated rabbits are nonseasonal breeders and produce multiple offspring in one litter. These reproductive patterns make the use of rabbits for reproductive research highly efficient.”

----
Here are some links i (sum) found which may help. Need to go through all the info and sort it out, But there are a couple of good diagrams.

'''Links for group assignment'''

http://www.reproduction-online.org/cgi/reprint/48/1/43

http://books.google.com/books?id=RY0rXE2HgqsC&pg=PA344&dq=rabbit+embryo+stages&as_brr=3#v=onepage&q=rabbit%20embryo%20stages&f=false - good for what studies in rabbit embryo have been used for. And has a good table for embryological stages!!

http://books.google.com/books?id=ljAKtC-iIrIC&pg=PA264&dq=rabbit+embryo+stages&as_brr=3#v=onepage&q=rabbit%20embryo%20stages&f=false

http://books.google.com/books?id=73bbKzqRvLsC&pg=PA156&dq=rabbit+embryo+stages&lr=&as_brr=3#v=onepage&q=rabbit%20embryo%20stages&f=false - picture of implantation

http://books.google.com/books?id=aZ7DQYFyxswC&pg=PA122&dq=%22rabbit+development+stages%22&lr=&as_brr=3#v=onepage&q=&f=false
-------
Hi I(Juliana) uploaded file, you guys can have a look.
Go to 'Upload File' tab and click ' early growth of rabbit trophoblast' file.

-------------
also I found an interesting article!
'''An Electron Microscope Study of the Embryology of the Intercalated Disc in the Heart of the Rabbit'''
Alan R. Muir
The Journal of Biophysical and Biochemical Cytology, Vol. 3, No. 2 (Mar. 25, 1957), pp. 193-202
Published by: The Rockefeller University Press

http://info.library.unsw.edu.au/cgi-bin/local/access/ej-access.cgi?url=http://links.jstor.org/sici?origin=sfx%3Asfx&sici=0095-9901(1957)3%3A2%3C193%3AAEMSOT%3E2.0.CO%3B2-S
--

[[User:Z3126328|Jin Lee]] 10:48, 25 August 2009 (EST)

----------------
I found helpful book in the library
'''Bensley's Practical Anatomy of the Rabbit 8thE by E.Horne Craigie, Toronto, University of Toronto Press 1948'''
--[[User:Z3126328|Jin Lee]] 13:27, 27 August 2009 (EST)

==Vishnnu's Research==

'''Background reading (Vishnnu)'''

Hey everyone. I'm starting my background reading section where I shall describe my research resources. They contain a summary and a link to the resource itself. I shall keep this "notes" section updated with each new entry I add.

'''Notes:'''

*Articles 1 & 2 - Juliana this could be useful to you.

*Article 2 - Sum this could be useful to you.

*Articles 3 & 4 - Abnormal development articles (added: 02/09/2009)

*Articles 5 & 6 - Abnormal development articles (added: 13/09/2009)

'''Article 1'''

'''The rabbit as a model for reproductive and developmental toxicity studies''' --[[User:Z3187802|Vishnnu Shanmugam]] 21:05, 30 August 2009 (EST)

''Robert H. Foote and Edward W. Carney'' ''Reproductive Toxicology 14 (2000) 477–493'' ''Department of Animal Science, Cornell University, 204 Morrison Hall, Ithaca, New York 14853-4801, USA Developmental and Reproductive Toxicology, ''The Dow Chemical Company Midland, Michigan 48674, USA''

'''Summary'''

This is a review article of a study looking at the use of rabbits in toxicological studies. The article describes the advantages in using the rabbit experimental model as opposed to the rodent model (mice & rats) and outlines the differences that make toxicological studies on rabbit embryos more accurate than rodents to resemble similar toxicological effects in human embryos. The article describes various techniques that can be used (eg. blood collection from marginal ear vein, artificial insemination, embryo collection) and solutions to some common problems that researchers face when using animal models. Very interesting article with a great quote from Robert Koch to open the eyes of researchers to other animal models:

“Gentlemen, never forget that mice are not human beings”

Want to find out more? Follow the link!

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6TC0-41SBGDH-1&_user=37161&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_acct=C000004218&_version=1&_urlVersion=0&_userid=37161&md5=4db60dc9352996fc4865b9d781b0128d

'''Article 2'''

'''Developmental stages in the rabbit embryo: guidelines to choose an appropriate experimental model''' --[[User:Z3187802|Vishnnu Shanmugam]] 21:05, 30 August 2009 (EST)

''S. Beaudoin; P. Barbet; F. Bargy''
''Fetal Diagnosis and Therapy; Nov/Dec 2003; 18, 6; Academic Research Library''
''pg. 422''

'''Summary'''

The article describes the various stages in the developing rabbit embryo and the rationale for using rabbits to study normal and abnormal embryology. The article details normal developments in the rabbit embryo and compares it to the developing human embryo. By making this comparison the article argues for the validity of rabbit embryology to better understand human embryology and also suggests that due to the similarities in the developing rabbit and human embryos, experiments on rabbit embryo’s yield more reliable results for human embryology. The article has some rare images on normally developing rabbits and breaks the developmental stages down (in days) describing the observable characteristics that form (eg. Limb development & body formation).
I have decided to use the image provided in the journal.

Definitely worth reading people, follow the link!

http://content.karger.com/produktedb/produkte.asp?typ=fulltext&file=FDT2003018006422

'''Article 3'''

'''Acheiropodia is caused by a genomic deletion in C7orf2, the human orthologue of the Lmbr1 gene''' --[[User:Z3187802|Vishnnu Shanmugam]] 04:32, 2 September 2009 (EST)

''P. Ianakiev, M. J. van Baren, M. J. Daly, S. P. A. Toledo, M. G. Cavalcanti, J. Correa Neto, E. Lemos Silveira, A. Freire-Maia, P. Heutink, M. W. Kilpatrick, P. Tsipouras''
''Am. J. Hum. Genet. 68:38–45, 2001''
''Department of Pediatrics, University of Connecticut Health Center, Farmington, CT;''
''Department of Clinical Genetics, Erasmus University, Rotterdam;''
''Whitehead Institute for Biomedical Research, Cambridge, MA;''
''LIM/25-D, University of Sao Paulo School of Medicine,''
''And Private Practice, Sao Paulo;''
''Private Practice, Porto Alegre, Brazil;''
''Department of Genetics, UNESP-Universidade Estadual Paulista, Botucatu SP, Brazil''

'''Summary'''

The article describes the developmental abnormality Acheiropodia can be passed down genetically from parent to offspring. Acheiropodia (also known as Horn Kolb Syndrome) is a condition where the distal extremities of the embryo fail to form. Although it is not fatal, the individual endures a very difficult life without hands and feet. The article notes that the disorder only affects the development of the limbs and has no other reported manifestations. The article defines this to be an autosomal recessive disorder which means that two copies of an abnormal gene must be present in the affected individual in order for the disease to develop. Thus, each parent passes an abnormal gene to the offspring. It is interesting to note the process of the malformation from genotype to phenotype: small deletions on the chromosomes produce abnormal genes, the abnormal genes are then passed down to the offspring, the offspring that inherits two of the abnormal genes is unable to code for the correct proteins and as a result, there is failure in normal development of limb extremities in the embryo phenotype. The article also has a shocking image of an individual with Acheiropodia which highlights the extent to which it can impact a person’s life and the urgent need to find a cure.

Read more about the exact nature of the abnormal gene using the link.

http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=1109034

'''Article 4'''

'''Epidemiology of congenital clefts of the lip and palate''' --[[User:Z3187802|Vishnnu Shanmugam]] 04:32, 2 September 2009 (EST)

''JOHN C. GREENE'' ''D.M.D. ,M.P.H.'' ''Public Health Rep. 1963 July; 78(7): 589–602''

'''Summary'''

This review article combines research to study the factors causing the developmental abnormalities cleft palate and cleft lip in populations. “Cleft palate (palatoschisis)” and “cleft lip (cheiloschisis)” are the terms used to describe the non- fusion of the upper lip, hard or soft palate and typically occur during the gestation phase of embryonic development. The article tables the occurrence of cleft palate and cleft lip in populations of people in various cities across the world. It also compares the occurrence of cleft palate and cleft lip in males and females. The article finds that the incidence of cleft palate and cleft lip is:

*Is random in males and females (ie. Occurs approximately evenly in both sexes)

*Is random in people living in different cities

*Is higher in children of mothers over the age of 35

*Is higher in white populations and lower in the negro populations which suggests possible role of environmental factors

*No concrete proof that cleft palate and cleft lip is hereditary

*Is higher in rats exposed to radiation and those fed riboflavin

*Is higher in rabbits and other lab animals exposed to higher stress through cortisone injections

Although the article is now quite ancient, it is interesting to note the incidence of cleft palate and cleft lip among people. It also shows the historical foundation of research into the causes of cleft palate and cleft lip through animal experimentation.

Read more about cleft palate epidemiology using the link.

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1915191

'''Article 5'''

'''Chromosome abnormalities in human embryos''' --[[User:Z3187802|Vishnnu Shanmugam]] 00:10, 13 September 2009 (EST)

''Santiago Munne & Jaques Cohen The Center for Reproductive Medicine and science of Saint Barnabas Medical Center, New Jersey, USA Human Reproductive Update 1998, Vol. 4, No. 6 pp. 842-855 European Society of Human Reproduction and Embryology''

'''Summary'''

As the title suggests, this article focuses on chromosomal abnormalities in the developing human embryo. To understand this article, it is necessary to first establish some basic definitions that are used throughout the article. Aneuploidy can be defined as the occurrence of one or more extra or missing chromosomes leading to an unbalanced chromosome number. Although most babies with an unbalanced amount of chromosomal material miscarry during the first trimester of pregnancy, those that are born have crippling conditions such as:

* Birth defects

* Turner's syndrome (disorder where a female child is born with only 1 X chromosome)

* Down's syndrome (disorder where child is born with 3 copies of chromosome 21)

* Edward's syndrome (disorder where child is born with 3 copies of chromosome 18)

* Patau's syndrome (disorder where child is born with 3 copies of chromosome 13)

* Klinefelter's syndrome (disorder where male child is born with 2 copies of the X chromosome and 1 Y chromosome)

Polyploidy is a type of aneuploidy where the baby has three, four, or more sets of chromosomes instead of the two present in diploids. Chromosomal mosaicism is when different cells within an individual, who has developed from a single fertilized egg, have a different chromosomal makeup. Most commonly there will be some cells with a typical number of chromosomes (46 chromosomes) and other cells with an altered number or structure of chromosomes.

The article explores the possible causes of chromosomal abnormalities resulting from pregnancy though techniques such as IVF (In-Vitro Fertilization) and ICSI (Intracytoplasmic Sperm Injection). It also analyses the role of FSH (follicle stimulation hormone), temperature, water and light in chromosomal abnormalities.

The article finds:

* High FSH concentration increases likelihood of chromosomal abnormalities

* ICSI & IVF techniques have increased likelihood of chromosomal abnormalities

* Chromosomes exhibit temperature sensitivity and changes in temperature can cause chromosomal abnormalities

Although the article makes a number of findings, it is yet to be backed up with convincing evidence; the article has some really cool images of the developing embryo soon after fertilization. Overall, an interesting read.

Interested? Follow the link!

http://humupd.oxfordjournals.org/cgi/reprint/4/6/842.pdf

'''Article 6'''

'''Evaluation of the Safety and Pharmacokinetics of the Multi-Targeted Receptor Tyrosine Kinase Inhibitor Sunitinib During Embryo–Fetal Development in Rats and Rabbits''' --[[User:Z3187802|Vishnnu Shanmugam]] 00:10, 13 September 2009 (EST)

''S. Patyna, J. Haznedar, D. Morris, K. Freshwater, G. Peng, J. Sukbuntherng, G. Chmielewski, and D. Matsumoto''
''Pfizer Global Research and Development, San Diego, California''
''Roche LLC, Palo Alto, California''
''Pfizer Global Research and Development, Kalamazoo, Michigan''
''Xenoport Inc., Santa Clara, California''
''Pfizer Global Research and Development,'' ''Groton, Connecticut '' ''Birth Defects Research (Part B) 86:204–213 (2009)''

'''Summary'''

The article looks at how toxicity affects embryo-fetal development. The article describes the abnormal changes that occur when Sunitinib (an oral inhibitor of multiple receptor tyrosine kinases) is administered to pregnant rabbits and rats. This experiment was performed in an attempt to mirror the effects of antiangiogenic agents used in cancer treatment. Sunitinib is an antiangiogenic agent and the use of antiangiogenic agents is not recommended for treating cancer in pregnant patients because of the potential harm to embryo-fetal development. Angiogenesis (the formation of blood vessels) plays a critical role in embryo–fetal development and antiangiogenic agents slow down and/or stop the formation of blood vessels in order to control cancer and stop its spread. In pregnant patients however, this has the potential to adversely affect the developing embryo and these adverse effects is what is investigated in this article.

The article finds the antiangiogenic agent Sunitinib at toxic levels can result in:

* Embryo death

* Fetal skeletal malformations including vertebrae malformation and cleft lip/palate

* Teratogenic effects in rabbits

* Decreased maternal and fetal body weight

This article is a recent study and provides important findings regarding the use of antiangiogenic agents, especially during pregnancy. Although the maternal effects are minimal, the adverse effects to the embryo are significant and permanent. The article makes good use of tables and graphs to juxtapose pieces of information and to show trends. It is very interesting to note the extent to which chemicals can impact the vulnerable developing embryo.

Read more at link. (Use institutional login from UNSW computers)

http://www3.interscience.wiley.com/journal/122262246/abstract?CRETRY=1&SRETRY=0

------
thank you so much Vishnuu~~^^ from Juliana
-----
I also changed the format if you guys dont mind--[[User:Z3126328|Jin Lee]] 18:33, 31 August 2009 (EST)
----

Hey '''Vishnuu''', that link you found with the stages is awesome! thanks so much. Do you know if i am allowed to use the embryo pics in that article on our wiki page?? i'm not sure about the copyright rules. It says at the bottom of the article "Reproduced with permission of the copyright owner. Further reproduction prohibited without permission."
Does this mean we can only provide a link to it on our page? if so that's a shame, because those pics were fantastic!! '''SUM'''

Oh i also added an introduction - sum

Hey Sum,
Unfortunately, since its copyright protected we can't use the image directly......but there is a way of getting around it....You can modify the image using picture editing tools, then simply reference where the original picture came from and state that it has been modified by you. Alternatively, you can trace around the picture and provide only an outline (this will be very difficult to do with detailed pictures, a good picture editing software is recommended). Either way according to whats written under '''editing basics''' we need to include a picture that has been drawn up ourselves in the project. Also, not sure if you are aware, but the project is NOT due on Thursday (3rd September), Dr. Hill has very generously given everyone an extension till after mid-session break. --[[User:Z3187802|Vishnnu Shanmugam]] 02:35, 2 September 2009 (EST)

==Julianna's Research==
[http://netvet.wustl.edu/species/rabbits/rabtmodl.txt]
HISTORY OF THE RABBIT (IN RESEARCH)

A. Discovered in Spain about 100 B.C.
B. Domesticated in the 1500's
C. Standardization of breeds in 1800's
1. Research Uses
a. 1852: Rabbits have DL-hyoscyamine
(a) Can survive belladonna
(b) Endogenous atropine esterase
b. 1884: Pasteur develops rabies vaccine
c. 1891: Heape performs embryo transfer
(a) Influence on phenotype of the
uterine environment
d. 1908: Ignatowsky produces atherosclerosis
(a) Fed diets of milk, meat, and
eggs
(b) Produced intimal lesions
(c) Believed lesions due to protein
e. 1928: Demonstrated intranuclear development
of herpes virus
f. Graafian follicle was first observed
g. Coat colors and Mendelian inheritance
h. Immunology studies
i. Testing of human use products
j. Basic science studies
k. Diagnostic requirements
l. Eye Research
m. Pyrogen testing
n. Fetal drug induced teratology
o. Parasite research

LITERATURE REVIEW OF RABBIT USE

A. 1956 to 1800 ... Over 8000 citations
B. 1966 to 1987 ... 130,000 citations linking the rabbit to
all areas of research
C. 1988 to present ... 821 citations under the search
criteria: Rabbit: Model: Human Disease
D. Numbers of Rabbits Used (APHIS; ILAR records 1989)

1967 504,500
1978 439,986
1982 547,312
1983 466,810
1984 529,101
1985 544,621
1986 521,773
1987 534,385

ADVANTAGES OF USING RABBITS
A. Provides repeatability of animal model studies
B. Large enough for single samples
C. Many stocks/strains as animal models
D. Easily managed
E. Quality of immunologic products
F. Ease of reproductive control

DISADVANTAGES OF USING RABBITS
A. Most colonies are a storehouse of diseases
B. Extremely variable to responses to general anesthetics

[http://www.ncbi.nlm.nih.gov/pubmed/18430597]
The rabbit as a model to study asthma and other lung diseases.Keir S, Page C.
Sackler Institute of Pulmonary Pharmacology, Division of Pharmaceutical Sciences, 5th Floor Hodgkin Building, King's College London, Guy's Campus, London SE1 9RT, UK.

No single animal model is able to reproduce all the features of human asthma. However, the similarities between neonatally immunised rabbits and human asthma highlight the value of this model in the investigation of asthma pathophysiology and in the development of therapeutic agents. Airway inflammation and airway responses to various stimuli including histamine, adenosine 5'monophosphte and antigen in allergic rabbits have shown similarities with the responses observed in asthmatics. Furthermore, functional studies in rabbit airways show they are poorly responsive to capsaicin as are human airways. Chronic pre-treatment with capsaicin desensitises the TRPV(1) receptor enabling studies into the effect of this drug in both rabbits and man. The allergic rabbit model has been used extensively in assessing the various classes of anti-asthma drugs and is sensitive to similar drugs as patients with asthma, including beta-adrenoceptor agonists, corticosteroids, phosphodiesterase inhibitors and theophylline. This article highlights the usefulness of the rabbit as a species to study lung biology.

[http://www.ncbi.nlm.nih.gov/pubmed/8447943]
Effects of strain and embryo transfer model (embryos from one versus two donor does/recipient) on results of cryopreservation in rabbit.Vicente JS, García-Ximénez F.
Departamento de Ciencia Animal, Universidad Politécnica de Valencia, Spain.

Differential effects of 2 transfer models for normal thawed embryos of 1 donor doe were studied on the offspring rate and their embryo survival at birth from 3 selected rabbit strains (SY and SB: synthetic strains, NZ: New Zealand White). Morulae were obtained 64-66 h post-coitum from 93 adult does treated with 25 IU of hCG (SY:36, NZ:27, SB:30). Morphologically normal morulae were frozen in the presence of 1.5M DMSO and stored in liquid nitrogen. Normal thawed embryos were transferred into the oviducts of synchronized recipient does of the same strain 48 h after being injected with 25 IU of hCG (SY:28, NZ:21, SB:24). Each recipient received embryos from 1 (single transfer) or 2 different donor does (double transfer). Significant differences were observed in the post-thawing percentage of normal embryos between strains (SY:95 +/- 1% and SB:85 +/- 3%, P < 0.05; NZ: ,91 +/- 2%). After transfer, no significant differences were observed in pregnancy rate and offspring rate between the transfer models, whereas significant differences were only found in survival rate when all transfers were analyzed (double: 24 +/- 4% vs single: 14 +/- 3%, P < 0.05). An effect of strain was detected in the pregnancy rate (NZ: 33% vs SB: 71%, P < 0.05; SY: 61%) and in the survival rate per donor doe on pregnant recipient doe (SY: 42 +/- 5 vs SB: 19 +/- 5, P < 0.05; NZ: 34 +/- 7%). These results suggest a differential embryo sensitivity with respect to their genetic origin in both the freezing-thawing and transfer procedures.

--[[User:Z3126328|Jin Lee]] 13:06, 3 September 2009 (EST)

[http://www.ncbi.nlm.nih.gov/pubmed/14064965?log$=activity]GROSS EFFECTS ON RABBIT EMBRYOS AND MEMBRANES OF X-IRRADIATION IN THE BLASTOCYST STAGE.

[http://www.ncbi.nlm.nih.gov/pubmed/11139224?ordinalpos=408&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum]Onset of zygotic transcription and maternal transcript legacy in the rabbit embryo.Brunet-Simon A, Henrion G, Renard JP, Duranthon V.
Laboratoire de Biologie du Développement, INRA, Jouy en Josas Cedex, France.

Onset of zygotic transcription is progressive from the one-cell stage onward in the rabbit embryo. Maternal transcripts remain fairly stable until the 8-16 cell stage when major transcriptional activation of the zygotic genome takes place. To understand the mechanisms of the maternal-to-zygotic transition in the genetic information governing development, we asked whether a progressive synthesis of zygotic transcripts takes over the maternal molecules, or whether the synthesis of zygotic transcripts is very abrupt and independent of the persistence of the maternal counterparts. To answer this question, we set up mRNA differential display experiments comparing the mRNA content of rabbit embryos at different stages during the preimplantation period. We isolated eight zygotic transcripts whose synthesis is abruptly turned on at the 8-16 cell stage. These transcripts are involved in general cellular metabolism and their maternal counterparts are still present up to the four-cell and even the 8-16 cell stage. This identification of early zygotic transcripts suggests that global long range modifications of chromatin structure result in a rapid increase in transcription rates during the major transcriptional activation of the zygotic genome.

[http://www.ncbi.nlm.nih.gov/pubmed/11245264?ordinalpos=409&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum]
Reconstruction of the heteroparental diploid condition in rabbit zygotes by nuclear transfer.Escribá MJ, García-Ximénez F.
Departamento de Ciencia Animal Universidad Politécnica de Valencia, Spain. mescriba@dca.upv.es

Studies on genomic imprinting showed that parental genomes have complementary roles during embryogenesis, are both essential and need to be synchronized in their embryonic stage for successful development to term. To our knowledge, these studies have not been performed in species other than mice. We studied the in vitro and in vivo development of reconstructed zygotes by combining female haploid nuclear donors and androgenetic hemizygous recipients. Haploid donor embryos at the 8- or 32-cell stage were obtained from electroactivated young rabbit ova (eight pulses maximum, consisting of 0 6 kVcm(-1) for 60 microsec each, 38 min apart) which were further cultured for 24 h or 32 h. Couplets formed by both the haploid male hemizygous recipients and haploid female donor cells were electrofused (2.2 kVcm(-1) for 60 microsec duration each, 30 min apart) and their nuclear configuration determined 122 of those fused (43%: 122/286) were diploid. Reconstructed diploid zygotes developed in vitro up to the compacted morula, blastocyst and hatched stages (1/8-nuclei x 50%, 18% and 9% vs. 1/32-nuclei: 47%, 25% and 19%; P > 0.05), respectively. In embryo transfer assays, both 1/32-reconstructed zygotes and control, non-manipulated zygotes were transferred to synchronized does Four live reconstructed fetuses (4/49: 8 1% survival rate) and five in regression stage (9/49: 18% implantation rate) were observed on Day 21 post-ovulation, whereas from control zygotes, 11 fetuses were alive (11/53 21% fetal survival rate) and 2 degenerated (13/53 x 24 5% implantation rate). Similar results were obtained from a final experiment, in which development was allowed to progress to term. Six live rabbit pups derived front experimentally reconstructed zygotes (11%; 6/54) and three fetuses in regression stage were obtained; values slightly lower than those derived from non-manipulated and transferred control zygotes (18% 9/50, live born rate).

[http://www.ncbi.nlm.nih.gov/pubmed/11589623?ordinalpos=412&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum]
Effects of leukaemia inhibitory factor on endometrial receptivity and its hormonal regulation in rabbits.Liu CQ, Yuan Y, Wang ZX.
Shanghai Institute of Planned Parenthood Research, Shanghai, P. R. China.

The effects of hormones on production of leukaemia inhibitory factor (LIF) and the uterine receptivity in rabbits were studied. In ovariectomised rabbits, LIF protein was not detected in control but upregulated by progesterone alone. Oestrogen had a slightly negative effect when the rabbits were treated with both oestrogen and progesterone. Mifepristone (Mi) inhibited the progesterone-stimulated production of LIF in rabbit uterus. The transfer of embryos to LIF-treated recipients significantly increased pregnancy rate (70%) and implantation rate (27%) as compared with control (pregnancy rate=40% and implantation rate=17%). The transfer of embryos to LIF and mifepristone-treated recipients significantly decreased pregnancy rate (30%) and implantation rate (9%). The results indicated that LIF protein had a beneficial effect on uterine receptivity and mifepristone prevented this effect. Copyright 2001 Academic Press.

[http://www.ncbi.nlm.nih.gov/pubmed/8447943]
Effects of strain and embryo transfer model (embryos from one versus two donor does/recipient) on results of cryopreservation in rabbit.Vicente JS, García-Ximénez F.
Departamento de Ciencia Animal, Universidad Politécnica de Valencia, Spain.

Differential effects of 2 transfer models for normal thawed embryos of 1 donor doe were studied on the offspring rate and their embryo survival at birth from 3 selected rabbit strains (SY and SB: synthetic strains, NZ: New Zealand White). Morulae were obtained 64-66 h post-coitum from 93 adult does treated with 25 IU of hCG (SY:36, NZ:27, SB:30). Morphologically normal morulae were frozen in the presence of 1.5M DMSO and stored in liquid nitrogen. Normal thawed embryos were transferred into the oviducts of synchronized recipient does of the same strain 48 h after being injected with 25 IU of hCG (SY:28, NZ:21, SB:24). Each recipient received embryos from 1 (single transfer) or 2 different donor does (double transfer). Significant differences were observed in the post-thawing percentage of normal embryos between strains (SY:95 +/- 1% and SB:85 +/- 3%, P < 0.05; NZ: ,91 +/- 2%). After transfer, no significant differences were observed in pregnancy rate and offspring rate between the transfer models, whereas significant differences were only found in survival rate when all transfers were analyzed (double: 24 +/- 4% vs single: 14 +/- 3%, P < 0.05). An effect of strain was detected in the pregnancy rate (NZ: 33% vs SB: 71%, P < 0.05; SY: 61%) and in the survival rate per donor doe on pregnant recipient doe (SY: 42 +/- 5 vs SB: 19 +/- 5, P < 0.05; NZ: 34 +/- 7%). These results suggest a differential embryo sensitivity with respect to their genetic origin in both the freezing-thawing and transfer procedures.

[http://www.ncbi.nlm.nih.gov/pubmed/14564113]
'''Developmental stages in the rabbit embryo: guidelines to choose an appropriate experimental model.'''Beaudoin S, Barbet P, Bargy F.
Department of Pediatric Surgery, Groupe Hospitalier Cochin-Saint-Vincent de Paul, Paris, France. sylvie.beaudoine@svp.ap-hop-paris.fr

Researchers involved in the field of congenital malformations are often forced to work on an animal model. Both accurate description of its normal development and comparative staging with human development will be mandatory. To complete the lacking medical literature, we herein provide such data for the rabbit model. Sampled rabbit embryos were staged using the Carnegie criteria, in order first to determine if they were consistent with the rabbit developmental pattern, and second to compare this pattern with the human one. Our results show a suitable comparison of rabbits and humans in early developmental stages, except for the neural growth. Copyright 2003 S. Karger AG, Basel

Talk:2009 Group Project 1

2009-10-14T12:14:16Z

Z3185685: /* Actual Changes Made */

== Lab 10 ==
--[[User:Z3283499|Antonio Lee]] 10:52, 2 October 2009 (EST) Hi everyone, I will be working with you during the Lab10 Tutorial and here is the news link and PDF of the manuscript for your group exercise. I encourage you to read the paper before the tutorial. Also, please indicate next to the questions below (using either your initials or student number) which one of the four questions you wish to address.
:'''Group 1 :''' [http://www.nature.com/nature/journal/v461/n7262/full/461354a.html '''Developmental biology: Asexual healing'''] in Nature News and Views - Nature 461, 354-355 (17 September 2009) [[Media:ANAT2341_Lab10_2009_Group 1 Reading.pdf|Manuscript (PDF): Mitochondrial gene replacement in primate offspring and embryonic stem cells]]

:Question 1. What is the background to the existing problem / disease condition? --[[User:Z3187802|Vishnnu Shanmugam]] 22:12, 2 October 2009 (EST)

Mitochondria are found in all eukaryotic cells and contain their own genome (mitochondrial DNA or mtDNA). Unlike the nuclear genome, which is derived from both the egg and sperm at fertilization, the mtDNA in the embryo is derived almost exclusively from the egg; it is of maternal origin.

Mutations in mitochondrial DNA (mtDNA) can lead to a range of chronic incurable diseases such as myopathies, neurodegenerative diseases, diabetes, cancer and infertility. Mutations in mitochondrial DNA could also contribute to other diseases such as Alzheimer’s,
Parkinson’s and Huntington’s diseases

A normal cell should be homoplasmic in its mitochondrial DNA, that is it should only contain one type of mitochondrial DNA. But if the cell has two or more types of mitochondrial DNA (a mixture of normal and mutated DNA) it is known as heteroplasmic and can lead to a range of diseases. These genetic mutations can also be passed to offspring causing disease.
1 in 3,500–6,000 are at risk or presently have a disorder from mutations in mitochondrial DNA. Disease progresses slowly and there are no cure. Limitations in assessing the extent heteroplasmy and accuracy in calculating the risks of developing mtDNA related disease means that a new approach is needed to tackle the problem.

:Question 2. What approach / method did the research team take to tackle / improve the problem?--[[User:Z3126328|Jin Lee]] 12:31, 7 October 2009 (EST)
:Working with rhesus macaque monkeys, the authors reconstructed mature oocytes containing the nuclear genome from one oocyte and the mitochondrial genome from another. To do this they removed the nuclear genetic material from one oocyte, leaving behind all of the mitochondrial DNA, then transferred it to another oocyte whose nucleus had been removed (a cytoplast), but which contained a full complement of mitochondrial DNA.

:Question 3. What was the breakthrough / major advancement OR failure / drawback? and why might this be of significance?
::Drawbacks - --[[User:Z3186093|Jenny Guy]] 22:43, 7 October 2009 (EST)
:::There were difficulties in visualising and isolating the intact chromosomes, as well as the mtDNA being susceptible to damage and translocation/movement. Visualization became easier after the development of techniques for DNA staining with fluorophores and looking under UV light during embryo cloning by the SCNT (somatic cell nuclear transfer). Successful implementation to avoid damage to the cytoplast during spindle removal involved using polarized microscopy. (p368) --[[User:Z3186093|Jenny Guy]] 14:12, 8 October 2009 (EST)
:Question 4. What are the next steps in moving forward? What are the next or new hurdles to overcome?

==Actual Changes Made==

'''Concise Version:''' (Everyone add their changes here)
# Removed cleft palate and cleft lip section (Abnormal development) --[[User:Z3187802|Vishnnu Shanmugam]]
# Altered references (current research and abnormal development) --[[User:Z3187802|Vishnnu Shanmugam]]
# Added picture guide for transgenic rabbit --[[User:Z3187802|Vishnnu Shanmugam]]
# Added picture guide for rabbit cloning --[[User:Z3187802|Vishnnu Shanmugam]]
# Removed newspaper image of rabbit (Current research) --[[User:Z3187802|Vishnnu Shanmugam]]
# Formatted pictures and text to reduce gaps in the assignment (current research and abnormal development) --[[User:Z3187802|Vishnnu Shanmugam]]
# Corrected spelling mistakes in images (current research and abnormal development) --[[User:Z3187802|Vishnnu Shanmugam]]
# Reviewed all images and have written a summary, original source, copyright information (current research and abnormal development) --[[User:Z3187802|Vishnnu Shanmugam]]
# Formatted the look of the genetics section, including 'abnormalities' --[[User:Z3186093|Jenny Guy]] 16:31, 14 October 2009 (EST)
# Fiddled with position of images in genetics section --[[User:Z3186093|Jenny Guy]] 16:31, 14 October 2009 (EST)
# Fixed spelling mistake in History - Jin Lee
# Added images in table of stages. --[[User:Z3185685|Sumaiya Rahman]]
# Added to introduction and related it to the rest of the page.

'''Long Version:'''

--[[User:Z3187802|Vishnnu Shanmugam]] 23:46, 10 October 2009 (EST) Okies, all done. I'm going to review all my images and add summaries to them. Dr. Hill asked for a concise version to all the changes we make from the peer review process. I suggest everyone add their changes to the list I have started above and place your signature next to it.

--[[User:Z3186093|Jenny Guy]] 14:29, 10 October 2009 (EST)Hey vishnuu, i was thinking could you please alter
* the gaps between the spina bifida images (format this somehow with the images on the side and text on the other)
* the gap under "Brachydactylia & Acheiropodia"...maybe you have entered down too much????
cheers :)

--[[User:Z3187802|Vishnnu Shanmugam]] 21:27, 9 October 2009 (EST)Hey all. I have removed the newspaper image of rabbit (Due to copyright issues), and have replaced it with a series of images that guides the reader through the process of cloning a rabbit. I have NOT altered the text summarizing the creation of transgenic and clone rabbits as there are very important & detailed information which if removed puts complex processes in danger of oversimplification. I also corrected spelling mistakes in some images.

--[[User:Z3187802|Vishnnu Shanmugam]] 20:22, 7 October 2009 (EST) Hey gang. By popular demand (or the stress of reading) people want less text. I have removed the entire cleft palate & cleft lip section from abnormal development. For current research, I have also created a step by step picture guide for transgenic rabbit creation. It was initially meant to be a video, but this wiki page does not display (.gif) or (.mov) files. Sum, I remember that you did your references after me...so when I removed the cleft palate & cleft lip section, the references changed....so I have also adjusted your references accordingly. I don't think it is necessary to make all the changes outlined below as most comments are subjective (different people have different preferences) and seems like some comments were made because people had nothing else to propose.

--[[User:Z3126328|Jin Lee]] 10:01, 8 October 2009 (EST)Hi Guys, I have fixed spelling mistake and some people commented to make table form for advantages and disvantages section. But I liked the way I presented so I will leave in point form.

--[[User:Z3186093|Jenny Guy]] 14:32, 8 October 2009 (EST)
Hey! I looked at what i could change in the genetics section and decided to format a little. Our peers asked:
* genome information into a table - this is a little silly since there'd only be one column.
* Reformating in sections such as hitory and genetics. - have tried to do a little.
* Make pictures appear on the same side of page. maybe aligning the pics on either the left or right side instead of both left and right, and possibly putting them as thumbnails could also work. - i tried to put both of the chromosome images ont he same side (tried both left and right) but found that it looked terrible considering the size (which is needed to see it) as the text wouldnt fit around it very well.
* it will look much better if there is some work to be done for the structure of it especially the paragraph under the heading of 'abnormalities'. - am still in the process. not sure what else i can do since its in basic dot point form with not a large text to format. any ideas? or shall i leave it how it is now?
* maybe instead of writing the entire reference, you could just state The Broad Institute or just the people related to it - i feel that the entire team needs a mention since all people relate to it. noting just the broad institute is almost like noting a team of people here in unsw as just plainly "UNSW" which is just disrespectful.

==Things to work on noted by peers==

Hey, So the changes i will make will be in the introduction section. Also a lot of people have said to add pictures in the stages section to make it more interesting. I couldnt get permission to use the images so i bought tracing paper today! lol will try to draw them and see if they are ok enough to add. I think i am going to leave the timeline section as is because most people liked it. What do u guys think? --[[User:Z3185685|Sumaiya Rahman]] 15:31, 8 October 2009 (EST)

Sounds great Sum....Its gonna take some effort to trace it then scan it. GL --[[User:Z3187802|Vishnnu Shanmugam]] 21:37, 9 October 2009 (EST)

Hey guys,
I read through all the notes our peers have given us and summarised them into the following sections. Majority of them overlap (where ive put a new persons opinions in the same dot point over and over to stress the point on how many people noticed). Some things are easily changed, most of all i reckon its
# formatting
# pictures
# text to be more concise
So we just need to finalise all these minor things to improve our project. Please detail any changes you've made in the the heading above.
Cheers, --[[User:Z3186093|Jenny Guy]] 20:30, 7 October 2009 (EST)

INTRODUCTION
* a little too brief, more information needed
* For the first sentence (the characteristics that make the rabbit an excellent model for study), mention the section 'Why are we using rabbits?' under History section.
* For the second sentence (study that developed and improved micromanipulation techniques), mention the 'Transgenic Rabbit' section below under the genetics section. I've read the entire project page, and the introduction was the only place I found that was not precise enough (which is a great thing). These are minor things, but I think they will help with improving your project page.
*suggestion: Place the history section after the Introduction. This gives the viewer an overview of the use of the rabbit embryo. This way the viewer is first subjected to a few examples of the rabbit embryos use. It also allows him/her to understand where the rabbit embryo sits in with history. I guess this is a matter of personal preference.

HISTORY
* The advantages and Disadvantages would be better in a table. the history you might want to put the advantages and disadvantages into a table to make the page look a bit more tidy and easier to read when we go through it.
* The usage of rabbits for experimental models in science and medicine could be stated under the history section to allow background information for the readers to become aware of the topic and why the rabbit have been used to study specfic medical procedures and diseases.
* Spelling mistake under 'Discovery of Graafian Follicle', 2nd paragraph. I think it's previous instead of 'previcous'.
* Reformating in sections such as hitory and genetics. Make pictures appear on the same side of page.
* The history section can be improved if the infomation is expanded to give some more detailed background knowledge although i like the idea that the information is concise describing each scientists contribution towards the model.
* could be formatted to make the information stand out and a lot more appealing, I would recommend including pictures if possible that link to the text and making the advantages and disadvantages into a table rather than listing it.

TIMELINE
* more images to wholly understand. timeline/staging section was clear and concise, however it could be improved by adding more colour/pictures to maintain the readers' interest. The timeline and staging bits are very well written and clear but i think you should add a few images in there to match up with the text. Perhaps some pictures of embryos throughout development. Pictures for every stage would make it more visually attractive rather than just reading text. lack of pics in the timeline.
* It’s a little confusing that the development jumps back and forth according to the body part developing. Maybe it should be categorised according to time of development instead for greater clarity at first glance
* The timeline is just a little confusing, as its divided into development of different parts, which breaks the time flow.
* some of the information for the timeline section was too heavy for the page - would recommend only using some of the information on your actual page and having the rest as links to separate pages

STAGING
* pictures for stages would have been nice, unless there were none????
* a more even distribution of information, particularly more detail in the stages
* Provide pictures for individual stages. Get visual, and make the stages interesting to read. include pictures in the stages section.
* Staging section is also very well presented but the information presented in a table would even look better if there is use of some pictures to make it more interesting for its audience.
* staging section was very bland and would be more appealing with pictures. I dont think its necessary to cite your entire reference within the text

GENETICS
* genome information into a table
* Reformating in sections such as hitory and genetics.
* Make pictures appear on the same side of page. maybe aligning the pics on either the left or right side instead of both left and right, and possibly putting them as thumbnails could also work.
* it will look much better if there is some work to be done for the structure of it especially the paragraph under the heading of 'abnormalities'.
* maybe instead of writing the entire reference, you could just state The Broad Institute or just the people related to it

ABNORMAL DEVELOPMENT
* There is also a lot of content which might be alleviated by reducing the section on abnormal development. Too much information about the abnormalities. make more concise.
* the abnormalities went a bit over board, and didn't need that much attention I think (as compared witht the research which was good)
* reduce the writing content. for example. In the current research section, you have two scientific process of transgenic rabbits as well as cloning which is described in how these are done. why not draw a step by step diagram, and put these written steps in the link to the image.
* The information provided under Hydrocephalus and Brachydactylia was informative and interesting, but it contained too much text. I suggest you narrow it down and make use of Dots point, numbering, bold/italic words, and/or sub-sub-headings.
* Section for "Abnormal Development" gives the readers useful amount of information but i think its very lenghty, use of dot points can make it look even better and easy to understand.

CURRENT RESEARCH
* the group makes good usage of diagrams but towards the end diagrams die out, you might want to make the current research part of your assignment into diagrams and steps as there is just a bunch of information thrown there and alot of reading needed, if you put it into steps or diagrams it will make the marking process and reading process easier and allow us as reader to understand the information with ease.
* 'Transgenic Rabbit' should be shifted toward the genetic information on the rabbit. (Jenny - i dont agree with this as its research, not its offical genetics. Vishnnu - Neither do I)
* information in regard to stem cells should be brief and truncated. Example in regard to stem cell research should have brief and simple model explaining the process and why it used.
* There is too much information under stem cells. There is 2 examples of studies dealing with stem cells. A suggestion would be to just have one, and have a link saying 'Koga's research on Stem Cells'.
* Have the section 'links to Research labs and researchers' placed at the end of current research. That way, the information on the page will flow smoother.
* more of a focus on current research i.e. what each method is being used for and less on the process behind each method.
* great amount of information but in my perspective replacing the paragraphs with some dot points with heading and subheadings would further enrich understanding of readers.

OVERALL
* "As you start going down the page though the information starts to read a bit haphazardly, for example the developing body; jumping for section to section and the timeline section. it would be great if you could clean this up as it doesn't really flow." - formatting
* condense long slabs of text as the page is long
* format it so there are no huge gaps
* move the links to current research labs up closer to the current research section, just to keep it all together

==Constructive Criticism of Coordinator==
--[[User:S8600021|Mark Hill]] 08:07, 8 October 2009 (EST) The following comments are general in nature in no specific order, as it would be inappropriate to suggest specific changes and then assess the final project. Comments will be added during this week and you still have one week before final submission.

* There is no concise list of changes made to your project on the basis of peer assessments.
* Timeline of Embryo Development early stages, are in the introductory text said to be in hours, but it would be good to see it in the list as well.
* [[:File:Sizes.JPG]] Relative sizes, but no absolute size or scale given.
* A general comment about images. When you click an image and it opens, the information below the image should have an explanation of what the image shows, a reference (if from a paper) and a link to the original source (if available) as well as copyright information.
* Did you actually read the terms of use for this image that you cut n pated into the image description? [[:File:Rabbit_hybrid.jpg]] "For this purpose alone you may retrieve and display the Content on a computer screen. You may also print out, but not photocopy, one copy of individual files on paper and store files in electronic form on disc, but not on any server or any other storage device connected to a network where the Content could be accessed by other users." It clearly states that you cannot use this image online.
* Chromosomes section, images have no legends and structure not clearly organised.
* There needs to be better checking of your spelling and grammar, for example [[:File:Rabbitmalformation3.jpg]] "Plant Patkology of Tke Rockefeller Institute for Medical Researck", these mistakes while not major, suggests a lack of reviewing of your work by the group.
* Just a comment on project "feel", when several people work together on a project and insert their parts, the final project sometimes has an uneven style. Now that you have time to tidy up, try and get a common appearance throughout your project.

==Constructive Criticism of Peers==

--[[User:Z3218657|Sally Clarke]] 09:32, 1 October 2009 (EST)
Nice work Guys!
- Fantastic images used throughout - maybe a few more in the timeline so we can understand what is going on
- As you start going down the page though the information starts to read a bit haphazardly, for example the developing body; jumping for section to section and the timeline section. it would be great if you could clean this up as it doesn't really flow.
- The section on the abnormal development is great.
- The page is quite long - Maybe you could condense some of the text as it is kind of slab like
- i really enjoyed the breeding section
- The advantages and Disadvantages would be better in a table.

--[[User:Z3223194|Bronwyn Lewis-Jones]] 08:08, 1 October 2009 (EST) Hi Group 1! This is obviously a well organised and well researched assignment. I found it very informative. There are (of course) some things I feel could improve the overall submission. I loved that the timeline/staging section was clear and concise, however I think it could be improved by adding more colour/pictures to maintain the readers' interest. There is also a lot of content which might be alleviated by reducing the section on abnormal development. Hope this helps :)

--[[User:Z3218146|Julianna Lam]] 01:11, 1 October 2009 (EST) good job guys.
-Theres alot of relevant information.
-The timeline and staging bits are very well written and clear but i think you should add a few images in there to match up with the text.
-The image for the genetics bit is awesome.
-The page is nicely set out.
-Too much information about the abnormalities.

--[[User:Z3258567|Sando Rashed]] 20:04, 30 September 2009 (EST)hey guys, your page looks good, starts off well as there is not a bunch of information just thrown in, the information used is well thought, with the history you might want to put the advantages and disadvantages into a table to make the page look a bit more tidy and easier to read when we go through it (you can also do this with the info under genome), the group makes good usage of diagrams but towards the end diagrams die out, you might want to make the current research part of your assignment into diagrams and steps as there is just a bunch of information thrown there and alot of reading needed, if you put it into steps or diagrams it will make the marking process and reading process easier and allow us as reader to understand the information with ease, other than that the page looks quite good, well done on all your contributions

--[[User:Z3218792|Gabriela Pinget]] 21:51, 29 September 2009 (EST)

Nice page. I particularly liked the idea of lists of what is to come before each flood of information as was done with the ‘history of model use’ section.

- Nice easing into the topic with ‘advantages’ and ‘disadvantages’ lists.

- I liked the of rabbit embryo development to that of humans- puts it into perspective

- Good glossary- informative but not over- the- top

- Nice genetics section! Easy to read and a great use of illustrations to break up the information

- I also like that you took a page out of Mark’s book in the addition of the abnormalities section

Improvements:

- Perhaps some pictures of embryos throughout development.

- It’s a little confusing that the development jumps back and forth according to the body part developing. Maybe it should be categorised according to time of development instead for greater clarity at first glance

--[[User:Z3295026|Joe Nassif]] 17:01, 29 September 2009 (EST)

Your assessment has come along great in regard to the criteria format. There are a few alterations that could improve your project, the following alterations may enhance your wiki page:

'''-''' The usage of rabbits for experimental models in both science and medicine could be state under the history section to allow background information for the readers to become aware of the topic and why the rabbit have been used to study specfic medical procedures and diseases.

'''-''' Secondly the information on 'Transgenic Rabbit' should be shifted toward the genetic information on the rabbit. So far the project is looking and coming along great except for minor edits.

'''-''' Background information should be placed subsequent to the introduction allowing the reader to understand why this specific animal is used for specfic purposes.

'''-''' Figures/Graphs and the illustration of the anatomy and genetic development of the embryo were useful and clear allowing the viwers to understand and learn through the demonstration of pictures which were extremely informative.

'''-''' Genetics: the Genetics and Abnormalities information was great and very informative. It was great how the group compared the embryo with the human chromosome allowing the audience to understand the difference between both.

'''-''' Abnormalities: Information and details which were in the genetic section provided informative and interesting information, and it could be truncated a bit, additionally just discussing the chromosome development of the rabbit.

'''-''' Current Embryology Research: information in regard to stem cells should be brief and truncated. Example in regard to stem cell research should have brief and simple model explaining the process and why it used.

'''-''' Consequently, I thought the project was good it flowed and was very informative. The information was detailed, and the illustrations were useful and allowed the readers to gain a brief overview on the topic and it usage in history and in current research. Overall group 1 seem to achieve the critriea outcomes and summarised the topic really well, the comparsion to human embryo development througout the text was great and is a good referencing point in comparsion to the species choosen.
Great job --[[User:Z3295026|Joe Nassif]] 17:01, 29 September 2009 (EST)

--[[User:Z3255007|Sadaf Masood]] 12:09, 30 September 2009 (EST)Hello Group 1! Congrats on your awesome group project! I must say im very impressed with all the information you have posted and i have listed down the good bits and the bits that need to be improved. Since i am posting this a lil late, i have seen that u have already improved your project and few aspects...Good Job guys!

1. Very brief introduction...maybe just a little bit more info will be perfect

2. Abnormalities section is very informative and well researched, but very long, how about making it a little more precise?

3. The Advantages and Disadvantages of the using Rabbit is just simply perfect

4. The timeline is just a little confusing, as its divided into development of different parts, which breaks the time flow.

5. Pictures for every stage would make it more visually attractive rather than just reading text

6. Great Glossary!

There were few things earlier that need to be improved but you guys fixed it as soon as comments were posted so basically you guys rock :)An excellent effort guys. Best Wishes

# --[[User:Z3217015|Mitchell Mathieson]] 09:45, 25 September 2009 (EST)Very nice. The information was maybe a bit spread out, with heaps of gaps everywhere (formatting???), but the information was there, and relevant, and easy to read. I like how there was tonnes of information on current research, as I think that was the main aim, but the abnormalities went a bit over board, and didn't need that much attention I think. pictures for stages would have been nice, unless there were none???? The references are top notch, and the glossary is pretty amazing, and in the right place. Overall very good, I think formatting was the major downfall though, as it makes the page that much longer, and hence a little bit more difficult to read.

--[[User:Z3224449|Elide Newton]] 14:12, 26 September 2009 (EST)
HEllO GROUP 1: Well done on such a great assignemnt, looks like you have all worked very hard. Well my one point of constructive criticism would be to reduce the writing content. for example. In the current research section, you have two scientific process of transgenic rabbits as well as cloning which is described in how these are done. why not draw a step by step diagram, and put these written steps in the link to the image. that way it is more visual, the info is still there under the image link, and the page wont look as daunting to read. :) hope this helps!

--[[User:Z3254857|Begum Sonmez]] 00:46, 26 September 2009 (EST)
Hello Group 1. Firstly, I would like to let you all know that you have all done a great job. I'm impressed. I have a few suggestions that I think mite help to improve the page even more:

*Introduction:

1)For the first sentence (the characteristics that make the rabbit an excellent model for study), mention the section 'Why are we using rabbits?' under History section.

2)For the second sentence (study that developed and improved micromanipulation techniques), mention the 'Transgenic Rabbit' section below under the genetics section. I've read the entire project page, and the introduction was the only place I found that was not precise enough (which is a great thing). These are minor things, but I think they will help with improving your project page.

3)Breeding information was informative.

4) A suggestion: Place the history section after the Introduction. This gives the viewer an overview of the use of the rabbit embryo. This way the viewer is first subjected to a few examples of the rabbit embryos use. It also allows him/her to understand where the rabbit embryo sits in with history. I guess this is a matter of personal preference.

*Timeline:

1)Graphs, and the illustration of the zona pellucida and mucin coat were very clear and informative.

*Staging: I had no problems with it. The lack of information I think was a plus. It touched on the content in the Timeline section.

*History:

1) I loved the idea of the 'Disadvantages' of the rabbit embryo, it seemed unbiased. The brief timeline provided a clear and short summary.

2) Spelling mistake under 'Discovery of Graafian Follicle', 2nd paragraph. I think it's previous instead of 'previcous'. Also, the 2nd paragraph under this heading does not flow that well. Try rephrasing the 2nd sentence.

*Genetics:

The Genetics and Abnormalities section flow into eachother very well. I appreciated the comparison of the rabbit chromosome to the human chromosome.

*Abnormalities:

1) The information provided under Hydrocephalus and Brachydactylia was informative and interesting, but it contained too much text. I suggest you narrow it down and make use of Dots point, numbering, bold/italic words, and/or sub-sub-headings.

*Current Embryology Research:
1) There is too much information under stem cells. There is 2 examples of studies dealing with stem cells. A suggestion would be to just have one, and have a link saying 'Koga's research on Stem Cells'.

2) Have the section 'links to Research labs and researchers' placed at the end of current research. That way, the information on the page will flow smoother.

Overall, I thought there was a consistent structure in each section. The information was informative, and the pictures were relevant and helped me better understand the topics of discussion.

--[[User:Z3252340|Emily Wong]] 10:58, 27 September 2009 (EST) Firstly, great work. It is a well researched, structured and organised page. The content is very in depth and includes information on all of the specified areas. It is well referenced, with an extensive reference list indicating the amount of research put into the page. Some areas are more detailed than others. For example, the staging section is quite short and concise where as the Abnormal development section is extremely long considering it is not a needed topic. There is moderate use of pictures and diagrams, but more use could benefit the page as it may be able to negate some of the large slabs of text. The comparisons made between the human and the rabbit embryos are a good part of the project page. Each member of the group has contributed to the page and provided a lot of information on the section of content they were working on. What would improve this project is a more even distribution of information, particularly more detail in the stages, a few more diagrams or pictures to negate some of the text presented, more of a focus on current research i.e. what each method is being used for and less on the process behind each method.

--[[User:Z3126345|Gang Liu]] 14:26, 27 September 2009 (EST)In my opionion, this is a well constructed page. It includes major subheadings such as history, timeline, stages, genetics and current research. It is very concise and straightforward, which makes it easy to read. For example, a short introduction paragraph,"...the rabbit is an appropriate animal model as the results from many experiments are significant to that of other mammals, including humans.", explains to reader why rabbit is such a suitable model.

It also provides a logic flow. For example, in history of rabbit model use section, it has provided advangtages and disadvantages of model use. This is appropriate, as it demonstrates the significance of rabbit model use in scitific discovery. In addition, it has provided detailed background information for each discovery. This makes it interesting to read.

It is also important to compare development of embryo between rabbit and human. For example, "... the similarities of this developmental pattern in humans and rabbits, suggests that the same growth increment is required to achieve the same stage. The main difference observed between human rabbit gestational duration is due to the fetal growth phase...", this has suggested human and rabbit share many similarities. Not only this page has demonstrated detailed written information of timeline development, it also provided graphics to reinforce the concept. For example, the hand drawing of developing embryo. As well as the comparison between human embryo and rabbit embryo timeline development.

It is also interesting to learn that rabbits have 22 pairs of chromosome, whereas humans have 23 pairs of chromosome.

Sections such as abnormal development and current research have demonstrated extended research and understanding. For example, hydrocephalus, spina Bifida, stem cell research and cloning techniques. All of these have showed the in depth research in textbooks, journals and internet based literatures.

However, this page can be improved by considering the following points.

*Provide pictures for individual stages. Get visual, and make the stages interesting to read.

*Reformating in sections such as hitory and genetics. Make pictures appear on the same side of page.

*Typo: "A rabbits potential for reproduction..."

*Sections such as abnormal development and current research are too lengthy. Might consider shrink the content.

*Lack of glossary.

Overall, big thumbs up!

--[[User:Z3252231|Angama Yaquobi]] 01:12, 28 September 2009 (EST)
First of all i would like to congratulate all the team members for a great team work.
Well done guys!! The group project looks amazing, the information presented is very concise
and straight to the point which makes it very easy for the readers to grab
the important information that they need to enhance their knowledge.
I like the section of history, the information is very clear,
and i like the idea of providing some background knowledge to the readers
about the disadvantages of the use of rabbit.
The history section can be improved if the infomation is expanded
to give some more detailed background knowledge althought
i like the idea that the information is concise describing each
scientists contribution towards the model.
The section for timeline is impressive, in my perspective its a great idea to cover alot of content in a very smart way
which is by the use of subheadings to make it easy to understand for audience.
Staging section is also very well presented but the information presented
in a table would even look better if there is use of some pictures
to make it more interesting for its audience. Genetics section
is beautifully presented, all the information is there with some
amazing pictures but will look much better if there is some work to
be done for the structure of it especially the paragraph under the
heading of 'abnormalities'. Section for "Abnormal Development" gives
the readers useful amount of information but i think its very lenghty,
use of dot points can make it look even better and easy to understand.
The same for Current embryology research, great amount of information but
in my perspective replacing the paragraphs with some dot points with
heading and subheadings would further enrich understanding of readers.
Also glossary would complement the webpage. But overall,
great amount of information which shows alot of research
which has been done by all the team members. Well done guys!!

--[[User:Z3217686|Thomas Dangerfield]] 13:29, 28 September 2009 (EST) Hey guys! Good work on your assignment! Plenty of info which is good, and very well referenced. The glossary is a good idea too! I do agree with a few others about the lots of clear spaces in the formatting, and the lack of pics in the timeline though. Also under the genetics section, maybe aligning the pics on either the left or right side instead of both left and right, and possibly putting them as thumbnails could also work. In the abnormalities section, there might have been a little too much info that probably wasn't needed, but i do like the effort put in. Over all, possibly more time spent on formatting and determining which sections are more important and which sections may need to be limited. Other than those points, the whole assignment seemed very well done!

--[[User:Z3215682|Carly Mooney]] 11:32, 29 September 2009 (EST)
You assignment is visually appealing and the genetic information e.g. the number of chromosomes of a rabbit was very interesting.There are some additional sections you have added which really complement your assignment e.g the abnormalities and I really liked the advantages and disadvantages of using the rabbit model. The few suggestions I would make is to:
* include pictures in the stages section
*place the pictures throughout the text (e.g. to left or right). You did this up until abnormalities and I felt it broke the flow of the written text.
* and maybe move the links to current research labs up closer to the current research section, just to keep it all together.
Overall very impressive though.

--[[User:Z3220040|Joanne Raffel]] 15:25, 29 September 2009 (EST) Nice wikipage, the page looked interesting however I agree with some others that the formatting of the page was inconsistent. I thought the referencing was great but found it a bit confusing with the reference numbers after the paragraphs. I thought the subheadings werent distinct enough, especially in relation to the text, which made it difficult to read. The history section could be formatted to make the information stand out and a lot more appealing, I would recommend including pictures if possible that link to the text and making the advantages and disadvantages into a table rather than listing it. I especially liked the comparison between the rabbit and the human embryo, however some of the information for the timeline section was too heavy for the page, I would recommend only using some of the information on your actual page and having the rest as links to separate pages. The staging section was very bland and would be more appealing with pictures. I dont think its necessary to cite your entire reference within the text, especially in the genetics section, maybe instead of writing the entire reference, you could just state The Broad Institute or just the people related to it. The abnormalities section was a good inclusion however it was very extensive, along with the current research section. Overall a very good wikipage.

----
*Hey, Well done guys!!! I think our group worked pretty well! I think we communicated each other well and did very best for their section. I fixed my spelling mistake and problem with sentence! As Begum mentioned, I think placing the history part after the introduction is better idea. --[[User:Z3126328|Jin Lee]] 13:36, 26 September 2009 (EST)

*Hey guys,
the project has come together brilliantly! it looks quite good. Hopefully mark will like it! ill add some terms to the glossary and try do some formatting (the first image is a little too big i think!) --[[User:Z3186093|Jenny Guy]] 10:28, 24 September 2009 (EST)

Hey. Yep all good. I had to get rid of the pics, so stages table is now blank. Im pretty much done. I'll see what i can add to the glossary. thanks :)--[[User:Z3185685|Sumaiya Rahman]] 23:34, 23 September 2009 (EST)

Hey all, I'm going to start a glossary and add it under the reference section. Scan your text and add to the glossary in alphabetical order. Also under the marking criteria, it says to provide links to researchers and research laboratories.....i'll start that under the glossary. Everyone else OK with their stuff?--[[User:Z3187802|Vishnnu Shanmugam]] 23:08, 23 September 2009 (EST)

Hey Sum, The images look fine but I don't think you can use the images like that since the journal KARGER is being particular about its copyright laws. I tried tracing around the images but it does not seem to resemble anything like an embryo. I did however find this link...go to it and scroll down to the images of the developing embryo. You might be able to edit it to resemble rabbit embryo. --[[User:Z3187802|Vishnnu Shanmugam]] 15:10, 23 September 2009 (EST). To get to the link, Google image search "rabbit gestation"....click on the "rabbit,gestation age" image from nature.com
Also google image search "The Haeckel embryo sequence"...could be useful after some editing

oh my god!! I summarised all of my research and wrote down on the page. Then I blew up everything!!!
it says 'edit conflict' what da?? I lost all of my work...it was my stupid mistake...--[[User:Z3126328|Jin Lee]] 01:06, 23 September 2009 (EST)

Oh also.. let me know if the images look stupid --[[User:Z3185685|Sumaiya Rahman]] 00:34, 23 September 2009 (EST)

Hey thanks vishnuu. I put some images up in the stages table. I did edit the pictures, but im not sure if im allowed to use it like this? have a look and let me know. Also im not sure what is going on with the reference section seems kinda all over the place, so i havnt added mine in yet. Maybe we should fix that up somehow? :) oh LOL about the breeding rabbits bit! haha
--[[User:Z3185685|Sumaiya Rahman]] 00:31, 23 September 2009 (EST)

Hey Sum, Sorry for the late reply. For $330, I'd rather breed rabbits and take the photos myself. I had a look at the original images, what we can do is trace around the developing rabbit embryo using the pencil tool on an image editing software(eg. microsoft paint - already preloaded into most windows). Then upload the image to the assignment. Does your PC have adobe fireworks?...extremely good for tracing images. If not, have a go at it with microsoft paint....I shall also have a go at it, then I shall let you know on this discussion page at about 3PM t'morrow. If any good then I'll send it to your student email. If not, we discuss potential alternatives. good luck Sum! --[[User:Z3187802|Vishnnu Shanmugam]] 23:51, 22 September 2009 (EST)

Yep thats the article i used for the developmental stages and put in a table. I should have my timeline posted by end of today. I also couldn't get permission to use the pictures as they wanted about $330 for me to use it!! no thanks. I'll see if i can work it in somehow. Vishnuu did u have any ideas on editing the images?? --[[User:Z3185685|Sumaiya Rahman]] 12:29, 22 September 2009 (EST)

Have a look at this article, it's helpful for comparison bt rabbit and human in developmental stages!--[[User:Z3126328|Jin Lee]] 13:35, 21 September 2009 (EST)
*Sampled rabbit embryos were staged using the Carnegie criteria, in order first to determine if they were consistent with the rabbit developmental pattern, and second to compare this pattern with the human one. Our results show a suitable '''comparison of rabbits and humans in early developmental stages''', except for the neural growth.
[http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowAbstract&ArtikelNr=73136&Ausgabe=229537&ProduktNr=224239
]

Absolutely correct Juliana, my research articles and their links are labelled 1-6 so far, the rest is yours..... I'll fix it for you. A timeline image seems tricky and i'm unsure, send Dr. Hill an email on m.hill@unsw.edu.au and see what he says. We still have till thursday to finish everything, so don't be too worried....try to finish all your other stuff and leave the drawing of the timeline last.--[[User:Z3187802|Vishnnu Shanmugam]] 17:49, 20 September 2009 (EST)

*no.1-7 in reference section is mine. and I think links under Vishnnu's research on the discussion board is mine. let me know please. (I can't remember all of my researches)
I want to make a timeline image but I can't do it;;; I asked Mark few weeks ago but havn't replied yet....can somebody help me???--[[User:Z3126328|Jin Lee]] 17:26, 20 September 2009 (EST)

'''** Hey Jenny, dont worry!! the project is not due until next week! (24th) we will have it done by then!! I am still waiting for permission to use the pictures in my stages section, thats why it hasnt been done yet. Hopefully i can get permission, otherwise i'll have to draw them (or something) myself.''' --[[User:Z3185685|Sumaiya Rahman]] 14:03, 17 September 2009 (EST)

It says project due date 24th september.......if the due date had been brought forward why was it not posted on the project main page? --[[User:Z3187802|Vishnnu Shanmugam]] 13:48, 17 September 2009 (EST)

EVERYONE...WHY IS THE REST OF OUR PROJECT NOT DONE??
* vishnuu...its due TODAY!! how can you post things up next Monday? Please make sure youve referenced EVERY image and all text (i know youve said you need to do this...but its easiest done when writing the section as now you have to go back and find everything, insert numbers etc. Remember to put the reference in the reference section. For the current research section i thought this might help you (as during my lecture in another class they spoke about how rabbits are used in heart development. Is there anything that you've found to include this?). Also I found this website during my research so it may help you? [http://www.evergen.com/rabbit_experience.html/ Rabbit Experiments]
* sum - where is the timeline???? It doesn't exist? Where is it? Also, we need some sort of visual for the staging. Have you found an images? Could you draw the stages of embryo development? It just looks incredibly boring.
* julianna...you need to put up more other than just two historians...there is NO referencing whatsoever in your entire section. where have you found this information? have you put it in your own words or copied it? You need to add some more refences to the reference section at the bottom..there just aren't many to back up your research.

seriously guys. ive added photos and tried to spice up the project but i am NOT going to finish your sections for you. ITS DUE IN 3 HRS! i cant believe you guys haven't bothered to even try finish this. Im very disappointed and i think its slack to let the team down. --[[User:Z3186093|Jenny Guy]] 10:34, 17 September 2009 (EST)

----

Hey all, just need to finish editing the current research part before i post it up, also need to edit some of my images under abnormal development and also references. Should be all done by Monday. --[[User:Z3187802|Vishnnu Shanmugam]] 07:02, 17 September 2009 (EST)

--[[User:S8600021|Mark Hill]] 01:40, 8 September 2009 (EST) OK guys, this is still just a page of text......

--[[User:Z3126328|Jin Lee]] 14:50, 3 September 2009 (EST) I want to make a timeline?

--[[User:S8600021|Mark Hill]] 08:42, 21 August 2009 (EST) z3187802 has contacted me and has been away sick. He should still complete his components of the group project.

Our group is Sum, Vishnnu, Juliana and Jenny. Today in the lab we have decided to research the RABBIT! [http://embryology.med.unsw.edu.au/OtherEmb/Rabbit.htm/ Rabbit embryology from Mark Hill]

(Juliana's email belebele85@msn.com)

----
This is apparently what we need to include in our case study:
#Timeline of Embryo Development - how long (SUM)
#Staging - are there species specific staging, what occurs when (SUM)
#History of Model Use - when was it first used, (JULIANNA)
#Genetics - chromosome number, sequencing (JENNY)
#Abnormal Development (VISHNNU)
#Current Embryology Research - research papers and findings (VISHNNU)

Hey guys, maybe we should add a section comparing rabbit to human development
--[[User:Z3185685|Sumaiya Rahman]] 16:45, 6 August 2009 (EST)

That sounds like a good idea Sum....seeing that human development is the primary theme of the course, not including it would be criminal!. -vishnnu

Report:
* Links to resources and discussions are to be posted on the group talk page, the project page is for the actual assignment
* Final assignment will be marked by another group and everyone will be given a marking criteria
* No information should be obtained from Wikipedia and all information (tables & graphs included) must be referenced
* Please feel free to suggest any further topics which can be included

== Research: ==
So i think the main rabbit used in research is the oryctolagus cuniculus. Lets focus mostly on that (or at least i, Jenny, will since im going genetics). This link is great for the specific genetics: [http://www.ncbi.nlm.nih.gov/nuccore/AJ001588/ Oryctolagus cuniculus complete mitochondrial genome]

Here's some stuff about benefits of modeling from a textbook. I haven't yet written as my own so its still the authors material. Just thought it might benefit us all (and raise our morale as we thought the rabbit might suck..but it doesn't!) We're not "submitting" this as our own work so technically we're not yet copyrighting their material.
Ive cited the book here and the website i got it from:
[http://books.google.com.au/books?id=RY0rXE2HgqsC&pg=PA344&lpg=PA344&dq=rabbit+embryology+genetics&source=bl&ots=rbr3CuBRxY&sig=p8055w9oYQmsQeuN78mgXBGmRK4&hl=en&ei=NI2KStaQJIvSsQOEpMjEDQ&sa=X&oi=book_result&ct=result&resnum=3#v=onepage&q=&f=false/ Cibelli, J., Lanza, R., Campbell, K. and West, M. 2002. Principles of Cloning. Academic Press]

“Rabbits were one of the first species in which blastomere nuclear transfer succeeded; as a model species, rabbits placed a central role in developing the micromanipulation technologies in embryos.” Other advantages for using rabbits are:

# “The costs to animal procurement, animal care, and oocyte production in rabbits are relatively low compared to large animals.” e.g. a cow embryo is 30x more expensive that a rabbit embryo
# “The developmental biology of rabbit embryos and fetuses resembles more closely that of large farm animals than that of rodent model species, including the transition from maternal to embryonic control of embryo development.”
# “The pregnancy of rabbits is relatively short (1 month), allowing rapid evaluation of fetal and postnatal development. In comparison, the gestation length for cattle is 9x longer.”
# “The sizeable milk production of rabbits allows their use as test animals for therapeutic protein expression in milk, or as a living bioreactor.”
# “Rabbits are induced ovulators. Domesticated rabbits are nonseasonal breeders and produce multiple offspring in one litter. These reproductive patterns make the use of rabbits for reproductive research highly efficient.”

----
Here are some links i (sum) found which may help. Need to go through all the info and sort it out, But there are a couple of good diagrams.

'''Links for group assignment'''

http://www.reproduction-online.org/cgi/reprint/48/1/43

http://books.google.com/books?id=RY0rXE2HgqsC&pg=PA344&dq=rabbit+embryo+stages&as_brr=3#v=onepage&q=rabbit%20embryo%20stages&f=false - good for what studies in rabbit embryo have been used for. And has a good table for embryological stages!!

http://books.google.com/books?id=ljAKtC-iIrIC&pg=PA264&dq=rabbit+embryo+stages&as_brr=3#v=onepage&q=rabbit%20embryo%20stages&f=false

http://books.google.com/books?id=73bbKzqRvLsC&pg=PA156&dq=rabbit+embryo+stages&lr=&as_brr=3#v=onepage&q=rabbit%20embryo%20stages&f=false - picture of implantation

http://books.google.com/books?id=aZ7DQYFyxswC&pg=PA122&dq=%22rabbit+development+stages%22&lr=&as_brr=3#v=onepage&q=&f=false
-------
Hi I(Juliana) uploaded file, you guys can have a look.
Go to 'Upload File' tab and click ' early growth of rabbit trophoblast' file.

-------------
also I found an interesting article!
'''An Electron Microscope Study of the Embryology of the Intercalated Disc in the Heart of the Rabbit'''
Alan R. Muir
The Journal of Biophysical and Biochemical Cytology, Vol. 3, No. 2 (Mar. 25, 1957), pp. 193-202
Published by: The Rockefeller University Press

http://info.library.unsw.edu.au/cgi-bin/local/access/ej-access.cgi?url=http://links.jstor.org/sici?origin=sfx%3Asfx&sici=0095-9901(1957)3%3A2%3C193%3AAEMSOT%3E2.0.CO%3B2-S
--

[[User:Z3126328|Jin Lee]] 10:48, 25 August 2009 (EST)

----------------
I found helpful book in the library
'''Bensley's Practical Anatomy of the Rabbit 8thE by E.Horne Craigie, Toronto, University of Toronto Press 1948'''
--[[User:Z3126328|Jin Lee]] 13:27, 27 August 2009 (EST)

==Vishnnu's Research==

'''Background reading (Vishnnu)'''

Hey everyone. I'm starting my background reading section where I shall describe my research resources. They contain a summary and a link to the resource itself. I shall keep this "notes" section updated with each new entry I add.

'''Notes:'''

*Articles 1 & 2 - Juliana this could be useful to you.

*Article 2 - Sum this could be useful to you.

*Articles 3 & 4 - Abnormal development articles (added: 02/09/2009)

*Articles 5 & 6 - Abnormal development articles (added: 13/09/2009)

'''Article 1'''

'''The rabbit as a model for reproductive and developmental toxicity studies''' --[[User:Z3187802|Vishnnu Shanmugam]] 21:05, 30 August 2009 (EST)

''Robert H. Foote and Edward W. Carney'' ''Reproductive Toxicology 14 (2000) 477–493'' ''Department of Animal Science, Cornell University, 204 Morrison Hall, Ithaca, New York 14853-4801, USA Developmental and Reproductive Toxicology, ''The Dow Chemical Company Midland, Michigan 48674, USA''

'''Summary'''

This is a review article of a study looking at the use of rabbits in toxicological studies. The article describes the advantages in using the rabbit experimental model as opposed to the rodent model (mice & rats) and outlines the differences that make toxicological studies on rabbit embryos more accurate than rodents to resemble similar toxicological effects in human embryos. The article describes various techniques that can be used (eg. blood collection from marginal ear vein, artificial insemination, embryo collection) and solutions to some common problems that researchers face when using animal models. Very interesting article with a great quote from Robert Koch to open the eyes of researchers to other animal models:

“Gentlemen, never forget that mice are not human beings”

Want to find out more? Follow the link!

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6TC0-41SBGDH-1&_user=37161&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_acct=C000004218&_version=1&_urlVersion=0&_userid=37161&md5=4db60dc9352996fc4865b9d781b0128d

'''Article 2'''

'''Developmental stages in the rabbit embryo: guidelines to choose an appropriate experimental model''' --[[User:Z3187802|Vishnnu Shanmugam]] 21:05, 30 August 2009 (EST)

''S. Beaudoin; P. Barbet; F. Bargy''
''Fetal Diagnosis and Therapy; Nov/Dec 2003; 18, 6; Academic Research Library''
''pg. 422''

'''Summary'''

The article describes the various stages in the developing rabbit embryo and the rationale for using rabbits to study normal and abnormal embryology. The article details normal developments in the rabbit embryo and compares it to the developing human embryo. By making this comparison the article argues for the validity of rabbit embryology to better understand human embryology and also suggests that due to the similarities in the developing rabbit and human embryos, experiments on rabbit embryo’s yield more reliable results for human embryology. The article has some rare images on normally developing rabbits and breaks the developmental stages down (in days) describing the observable characteristics that form (eg. Limb development & body formation).
I have decided to use the image provided in the journal.

Definitely worth reading people, follow the link!

http://content.karger.com/produktedb/produkte.asp?typ=fulltext&file=FDT2003018006422

'''Article 3'''

'''Acheiropodia is caused by a genomic deletion in C7orf2, the human orthologue of the Lmbr1 gene''' --[[User:Z3187802|Vishnnu Shanmugam]] 04:32, 2 September 2009 (EST)

''P. Ianakiev, M. J. van Baren, M. J. Daly, S. P. A. Toledo, M. G. Cavalcanti, J. Correa Neto, E. Lemos Silveira, A. Freire-Maia, P. Heutink, M. W. Kilpatrick, P. Tsipouras''
''Am. J. Hum. Genet. 68:38–45, 2001''
''Department of Pediatrics, University of Connecticut Health Center, Farmington, CT;''
''Department of Clinical Genetics, Erasmus University, Rotterdam;''
''Whitehead Institute for Biomedical Research, Cambridge, MA;''
''LIM/25-D, University of Sao Paulo School of Medicine,''
''And Private Practice, Sao Paulo;''
''Private Practice, Porto Alegre, Brazil;''
''Department of Genetics, UNESP-Universidade Estadual Paulista, Botucatu SP, Brazil''

'''Summary'''

The article describes the developmental abnormality Acheiropodia can be passed down genetically from parent to offspring. Acheiropodia (also known as Horn Kolb Syndrome) is a condition where the distal extremities of the embryo fail to form. Although it is not fatal, the individual endures a very difficult life without hands and feet. The article notes that the disorder only affects the development of the limbs and has no other reported manifestations. The article defines this to be an autosomal recessive disorder which means that two copies of an abnormal gene must be present in the affected individual in order for the disease to develop. Thus, each parent passes an abnormal gene to the offspring. It is interesting to note the process of the malformation from genotype to phenotype: small deletions on the chromosomes produce abnormal genes, the abnormal genes are then passed down to the offspring, the offspring that inherits two of the abnormal genes is unable to code for the correct proteins and as a result, there is failure in normal development of limb extremities in the embryo phenotype. The article also has a shocking image of an individual with Acheiropodia which highlights the extent to which it can impact a person’s life and the urgent need to find a cure.

Read more about the exact nature of the abnormal gene using the link.

http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=1109034

'''Article 4'''

'''Epidemiology of congenital clefts of the lip and palate''' --[[User:Z3187802|Vishnnu Shanmugam]] 04:32, 2 September 2009 (EST)

''JOHN C. GREENE'' ''D.M.D. ,M.P.H.'' ''Public Health Rep. 1963 July; 78(7): 589–602''

'''Summary'''

This review article combines research to study the factors causing the developmental abnormalities cleft palate and cleft lip in populations. “Cleft palate (palatoschisis)” and “cleft lip (cheiloschisis)” are the terms used to describe the non- fusion of the upper lip, hard or soft palate and typically occur during the gestation phase of embryonic development. The article tables the occurrence of cleft palate and cleft lip in populations of people in various cities across the world. It also compares the occurrence of cleft palate and cleft lip in males and females. The article finds that the incidence of cleft palate and cleft lip is:

*Is random in males and females (ie. Occurs approximately evenly in both sexes)

*Is random in people living in different cities

*Is higher in children of mothers over the age of 35

*Is higher in white populations and lower in the negro populations which suggests possible role of environmental factors

*No concrete proof that cleft palate and cleft lip is hereditary

*Is higher in rats exposed to radiation and those fed riboflavin

*Is higher in rabbits and other lab animals exposed to higher stress through cortisone injections

Although the article is now quite ancient, it is interesting to note the incidence of cleft palate and cleft lip among people. It also shows the historical foundation of research into the causes of cleft palate and cleft lip through animal experimentation.

Read more about cleft palate epidemiology using the link.

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1915191

'''Article 5'''

'''Chromosome abnormalities in human embryos''' --[[User:Z3187802|Vishnnu Shanmugam]] 00:10, 13 September 2009 (EST)

''Santiago Munne & Jaques Cohen The Center for Reproductive Medicine and science of Saint Barnabas Medical Center, New Jersey, USA Human Reproductive Update 1998, Vol. 4, No. 6 pp. 842-855 European Society of Human Reproduction and Embryology''

'''Summary'''

As the title suggests, this article focuses on chromosomal abnormalities in the developing human embryo. To understand this article, it is necessary to first establish some basic definitions that are used throughout the article. Aneuploidy can be defined as the occurrence of one or more extra or missing chromosomes leading to an unbalanced chromosome number. Although most babies with an unbalanced amount of chromosomal material miscarry during the first trimester of pregnancy, those that are born have crippling conditions such as:

* Birth defects

* Turner's syndrome (disorder where a female child is born with only 1 X chromosome)

* Down's syndrome (disorder where child is born with 3 copies of chromosome 21)

* Edward's syndrome (disorder where child is born with 3 copies of chromosome 18)

* Patau's syndrome (disorder where child is born with 3 copies of chromosome 13)

* Klinefelter's syndrome (disorder where male child is born with 2 copies of the X chromosome and 1 Y chromosome)

Polyploidy is a type of aneuploidy where the baby has three, four, or more sets of chromosomes instead of the two present in diploids. Chromosomal mosaicism is when different cells within an individual, who has developed from a single fertilized egg, have a different chromosomal makeup. Most commonly there will be some cells with a typical number of chromosomes (46 chromosomes) and other cells with an altered number or structure of chromosomes.

The article explores the possible causes of chromosomal abnormalities resulting from pregnancy though techniques such as IVF (In-Vitro Fertilization) and ICSI (Intracytoplasmic Sperm Injection). It also analyses the role of FSH (follicle stimulation hormone), temperature, water and light in chromosomal abnormalities.

The article finds:

* High FSH concentration increases likelihood of chromosomal abnormalities

* ICSI & IVF techniques have increased likelihood of chromosomal abnormalities

* Chromosomes exhibit temperature sensitivity and changes in temperature can cause chromosomal abnormalities

Although the article makes a number of findings, it is yet to be backed up with convincing evidence; the article has some really cool images of the developing embryo soon after fertilization. Overall, an interesting read.

Interested? Follow the link!

http://humupd.oxfordjournals.org/cgi/reprint/4/6/842.pdf

'''Article 6'''

'''Evaluation of the Safety and Pharmacokinetics of the Multi-Targeted Receptor Tyrosine Kinase Inhibitor Sunitinib During Embryo–Fetal Development in Rats and Rabbits''' --[[User:Z3187802|Vishnnu Shanmugam]] 00:10, 13 September 2009 (EST)

''S. Patyna, J. Haznedar, D. Morris, K. Freshwater, G. Peng, J. Sukbuntherng, G. Chmielewski, and D. Matsumoto''
''Pfizer Global Research and Development, San Diego, California''
''Roche LLC, Palo Alto, California''
''Pfizer Global Research and Development, Kalamazoo, Michigan''
''Xenoport Inc., Santa Clara, California''
''Pfizer Global Research and Development,'' ''Groton, Connecticut '' ''Birth Defects Research (Part B) 86:204–213 (2009)''

'''Summary'''

The article looks at how toxicity affects embryo-fetal development. The article describes the abnormal changes that occur when Sunitinib (an oral inhibitor of multiple receptor tyrosine kinases) is administered to pregnant rabbits and rats. This experiment was performed in an attempt to mirror the effects of antiangiogenic agents used in cancer treatment. Sunitinib is an antiangiogenic agent and the use of antiangiogenic agents is not recommended for treating cancer in pregnant patients because of the potential harm to embryo-fetal development. Angiogenesis (the formation of blood vessels) plays a critical role in embryo–fetal development and antiangiogenic agents slow down and/or stop the formation of blood vessels in order to control cancer and stop its spread. In pregnant patients however, this has the potential to adversely affect the developing embryo and these adverse effects is what is investigated in this article.

The article finds the antiangiogenic agent Sunitinib at toxic levels can result in:

* Embryo death

* Fetal skeletal malformations including vertebrae malformation and cleft lip/palate

* Teratogenic effects in rabbits

* Decreased maternal and fetal body weight

This article is a recent study and provides important findings regarding the use of antiangiogenic agents, especially during pregnancy. Although the maternal effects are minimal, the adverse effects to the embryo are significant and permanent. The article makes good use of tables and graphs to juxtapose pieces of information and to show trends. It is very interesting to note the extent to which chemicals can impact the vulnerable developing embryo.

Read more at link. (Use institutional login from UNSW computers)

http://www3.interscience.wiley.com/journal/122262246/abstract?CRETRY=1&SRETRY=0

------
thank you so much Vishnuu~~^^ from Juliana
-----
I also changed the format if you guys dont mind--[[User:Z3126328|Jin Lee]] 18:33, 31 August 2009 (EST)
----

Hey '''Vishnuu''', that link you found with the stages is awesome! thanks so much. Do you know if i am allowed to use the embryo pics in that article on our wiki page?? i'm not sure about the copyright rules. It says at the bottom of the article "Reproduced with permission of the copyright owner. Further reproduction prohibited without permission."
Does this mean we can only provide a link to it on our page? if so that's a shame, because those pics were fantastic!! '''SUM'''

Oh i also added an introduction - sum

Hey Sum,
Unfortunately, since its copyright protected we can't use the image directly......but there is a way of getting around it....You can modify the image using picture editing tools, then simply reference where the original picture came from and state that it has been modified by you. Alternatively, you can trace around the picture and provide only an outline (this will be very difficult to do with detailed pictures, a good picture editing software is recommended). Either way according to whats written under '''editing basics''' we need to include a picture that has been drawn up ourselves in the project. Also, not sure if you are aware, but the project is NOT due on Thursday (3rd September), Dr. Hill has very generously given everyone an extension till after mid-session break. --[[User:Z3187802|Vishnnu Shanmugam]] 02:35, 2 September 2009 (EST)

==Julianna's Research==
[http://netvet.wustl.edu/species/rabbits/rabtmodl.txt]
HISTORY OF THE RABBIT (IN RESEARCH)

A. Discovered in Spain about 100 B.C.
B. Domesticated in the 1500's
C. Standardization of breeds in 1800's
1. Research Uses
a. 1852: Rabbits have DL-hyoscyamine
(a) Can survive belladonna
(b) Endogenous atropine esterase
b. 1884: Pasteur develops rabies vaccine
c. 1891: Heape performs embryo transfer
(a) Influence on phenotype of the
uterine environment
d. 1908: Ignatowsky produces atherosclerosis
(a) Fed diets of milk, meat, and
eggs
(b) Produced intimal lesions
(c) Believed lesions due to protein
e. 1928: Demonstrated intranuclear development
of herpes virus
f. Graafian follicle was first observed
g. Coat colors and Mendelian inheritance
h. Immunology studies
i. Testing of human use products
j. Basic science studies
k. Diagnostic requirements
l. Eye Research
m. Pyrogen testing
n. Fetal drug induced teratology
o. Parasite research

LITERATURE REVIEW OF RABBIT USE

A. 1956 to 1800 ... Over 8000 citations
B. 1966 to 1987 ... 130,000 citations linking the rabbit to
all areas of research
C. 1988 to present ... 821 citations under the search
criteria: Rabbit: Model: Human Disease
D. Numbers of Rabbits Used (APHIS; ILAR records 1989)

1967 504,500
1978 439,986
1982 547,312
1983 466,810
1984 529,101
1985 544,621
1986 521,773
1987 534,385

ADVANTAGES OF USING RABBITS
A. Provides repeatability of animal model studies
B. Large enough for single samples
C. Many stocks/strains as animal models
D. Easily managed
E. Quality of immunologic products
F. Ease of reproductive control

DISADVANTAGES OF USING RABBITS
A. Most colonies are a storehouse of diseases
B. Extremely variable to responses to general anesthetics

[http://www.ncbi.nlm.nih.gov/pubmed/18430597]
The rabbit as a model to study asthma and other lung diseases.Keir S, Page C.
Sackler Institute of Pulmonary Pharmacology, Division of Pharmaceutical Sciences, 5th Floor Hodgkin Building, King's College London, Guy's Campus, London SE1 9RT, UK.

No single animal model is able to reproduce all the features of human asthma. However, the similarities between neonatally immunised rabbits and human asthma highlight the value of this model in the investigation of asthma pathophysiology and in the development of therapeutic agents. Airway inflammation and airway responses to various stimuli including histamine, adenosine 5'monophosphte and antigen in allergic rabbits have shown similarities with the responses observed in asthmatics. Furthermore, functional studies in rabbit airways show they are poorly responsive to capsaicin as are human airways. Chronic pre-treatment with capsaicin desensitises the TRPV(1) receptor enabling studies into the effect of this drug in both rabbits and man. The allergic rabbit model has been used extensively in assessing the various classes of anti-asthma drugs and is sensitive to similar drugs as patients with asthma, including beta-adrenoceptor agonists, corticosteroids, phosphodiesterase inhibitors and theophylline. This article highlights the usefulness of the rabbit as a species to study lung biology.

[http://www.ncbi.nlm.nih.gov/pubmed/8447943]
Effects of strain and embryo transfer model (embryos from one versus two donor does/recipient) on results of cryopreservation in rabbit.Vicente JS, García-Ximénez F.
Departamento de Ciencia Animal, Universidad Politécnica de Valencia, Spain.

Differential effects of 2 transfer models for normal thawed embryos of 1 donor doe were studied on the offspring rate and their embryo survival at birth from 3 selected rabbit strains (SY and SB: synthetic strains, NZ: New Zealand White). Morulae were obtained 64-66 h post-coitum from 93 adult does treated with 25 IU of hCG (SY:36, NZ:27, SB:30). Morphologically normal morulae were frozen in the presence of 1.5M DMSO and stored in liquid nitrogen. Normal thawed embryos were transferred into the oviducts of synchronized recipient does of the same strain 48 h after being injected with 25 IU of hCG (SY:28, NZ:21, SB:24). Each recipient received embryos from 1 (single transfer) or 2 different donor does (double transfer). Significant differences were observed in the post-thawing percentage of normal embryos between strains (SY:95 +/- 1% and SB:85 +/- 3%, P < 0.05; NZ: ,91 +/- 2%). After transfer, no significant differences were observed in pregnancy rate and offspring rate between the transfer models, whereas significant differences were only found in survival rate when all transfers were analyzed (double: 24 +/- 4% vs single: 14 +/- 3%, P < 0.05). An effect of strain was detected in the pregnancy rate (NZ: 33% vs SB: 71%, P < 0.05; SY: 61%) and in the survival rate per donor doe on pregnant recipient doe (SY: 42 +/- 5 vs SB: 19 +/- 5, P < 0.05; NZ: 34 +/- 7%). These results suggest a differential embryo sensitivity with respect to their genetic origin in both the freezing-thawing and transfer procedures.

--[[User:Z3126328|Jin Lee]] 13:06, 3 September 2009 (EST)

[http://www.ncbi.nlm.nih.gov/pubmed/14064965?log$=activity]GROSS EFFECTS ON RABBIT EMBRYOS AND MEMBRANES OF X-IRRADIATION IN THE BLASTOCYST STAGE.

[http://www.ncbi.nlm.nih.gov/pubmed/11139224?ordinalpos=408&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum]Onset of zygotic transcription and maternal transcript legacy in the rabbit embryo.Brunet-Simon A, Henrion G, Renard JP, Duranthon V.
Laboratoire de Biologie du Développement, INRA, Jouy en Josas Cedex, France.

Onset of zygotic transcription is progressive from the one-cell stage onward in the rabbit embryo. Maternal transcripts remain fairly stable until the 8-16 cell stage when major transcriptional activation of the zygotic genome takes place. To understand the mechanisms of the maternal-to-zygotic transition in the genetic information governing development, we asked whether a progressive synthesis of zygotic transcripts takes over the maternal molecules, or whether the synthesis of zygotic transcripts is very abrupt and independent of the persistence of the maternal counterparts. To answer this question, we set up mRNA differential display experiments comparing the mRNA content of rabbit embryos at different stages during the preimplantation period. We isolated eight zygotic transcripts whose synthesis is abruptly turned on at the 8-16 cell stage. These transcripts are involved in general cellular metabolism and their maternal counterparts are still present up to the four-cell and even the 8-16 cell stage. This identification of early zygotic transcripts suggests that global long range modifications of chromatin structure result in a rapid increase in transcription rates during the major transcriptional activation of the zygotic genome.

[http://www.ncbi.nlm.nih.gov/pubmed/11245264?ordinalpos=409&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum]
Reconstruction of the heteroparental diploid condition in rabbit zygotes by nuclear transfer.Escribá MJ, García-Ximénez F.
Departamento de Ciencia Animal Universidad Politécnica de Valencia, Spain. mescriba@dca.upv.es

Studies on genomic imprinting showed that parental genomes have complementary roles during embryogenesis, are both essential and need to be synchronized in their embryonic stage for successful development to term. To our knowledge, these studies have not been performed in species other than mice. We studied the in vitro and in vivo development of reconstructed zygotes by combining female haploid nuclear donors and androgenetic hemizygous recipients. Haploid donor embryos at the 8- or 32-cell stage were obtained from electroactivated young rabbit ova (eight pulses maximum, consisting of 0 6 kVcm(-1) for 60 microsec each, 38 min apart) which were further cultured for 24 h or 32 h. Couplets formed by both the haploid male hemizygous recipients and haploid female donor cells were electrofused (2.2 kVcm(-1) for 60 microsec duration each, 30 min apart) and their nuclear configuration determined 122 of those fused (43%: 122/286) were diploid. Reconstructed diploid zygotes developed in vitro up to the compacted morula, blastocyst and hatched stages (1/8-nuclei x 50%, 18% and 9% vs. 1/32-nuclei: 47%, 25% and 19%; P > 0.05), respectively. In embryo transfer assays, both 1/32-reconstructed zygotes and control, non-manipulated zygotes were transferred to synchronized does Four live reconstructed fetuses (4/49: 8 1% survival rate) and five in regression stage (9/49: 18% implantation rate) were observed on Day 21 post-ovulation, whereas from control zygotes, 11 fetuses were alive (11/53 21% fetal survival rate) and 2 degenerated (13/53 x 24 5% implantation rate). Similar results were obtained from a final experiment, in which development was allowed to progress to term. Six live rabbit pups derived front experimentally reconstructed zygotes (11%; 6/54) and three fetuses in regression stage were obtained; values slightly lower than those derived from non-manipulated and transferred control zygotes (18% 9/50, live born rate).

[http://www.ncbi.nlm.nih.gov/pubmed/11589623?ordinalpos=412&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum]
Effects of leukaemia inhibitory factor on endometrial receptivity and its hormonal regulation in rabbits.Liu CQ, Yuan Y, Wang ZX.
Shanghai Institute of Planned Parenthood Research, Shanghai, P. R. China.

The effects of hormones on production of leukaemia inhibitory factor (LIF) and the uterine receptivity in rabbits were studied. In ovariectomised rabbits, LIF protein was not detected in control but upregulated by progesterone alone. Oestrogen had a slightly negative effect when the rabbits were treated with both oestrogen and progesterone. Mifepristone (Mi) inhibited the progesterone-stimulated production of LIF in rabbit uterus. The transfer of embryos to LIF-treated recipients significantly increased pregnancy rate (70%) and implantation rate (27%) as compared with control (pregnancy rate=40% and implantation rate=17%). The transfer of embryos to LIF and mifepristone-treated recipients significantly decreased pregnancy rate (30%) and implantation rate (9%). The results indicated that LIF protein had a beneficial effect on uterine receptivity and mifepristone prevented this effect. Copyright 2001 Academic Press.

[http://www.ncbi.nlm.nih.gov/pubmed/8447943]
Effects of strain and embryo transfer model (embryos from one versus two donor does/recipient) on results of cryopreservation in rabbit.Vicente JS, García-Ximénez F.
Departamento de Ciencia Animal, Universidad Politécnica de Valencia, Spain.

Differential effects of 2 transfer models for normal thawed embryos of 1 donor doe were studied on the offspring rate and their embryo survival at birth from 3 selected rabbit strains (SY and SB: synthetic strains, NZ: New Zealand White). Morulae were obtained 64-66 h post-coitum from 93 adult does treated with 25 IU of hCG (SY:36, NZ:27, SB:30). Morphologically normal morulae were frozen in the presence of 1.5M DMSO and stored in liquid nitrogen. Normal thawed embryos were transferred into the oviducts of synchronized recipient does of the same strain 48 h after being injected with 25 IU of hCG (SY:28, NZ:21, SB:24). Each recipient received embryos from 1 (single transfer) or 2 different donor does (double transfer). Significant differences were observed in the post-thawing percentage of normal embryos between strains (SY:95 +/- 1% and SB:85 +/- 3%, P < 0.05; NZ: ,91 +/- 2%). After transfer, no significant differences were observed in pregnancy rate and offspring rate between the transfer models, whereas significant differences were only found in survival rate when all transfers were analyzed (double: 24 +/- 4% vs single: 14 +/- 3%, P < 0.05). An effect of strain was detected in the pregnancy rate (NZ: 33% vs SB: 71%, P < 0.05; SY: 61%) and in the survival rate per donor doe on pregnant recipient doe (SY: 42 +/- 5 vs SB: 19 +/- 5, P < 0.05; NZ: 34 +/- 7%). These results suggest a differential embryo sensitivity with respect to their genetic origin in both the freezing-thawing and transfer procedures.

[http://www.ncbi.nlm.nih.gov/pubmed/14564113]
'''Developmental stages in the rabbit embryo: guidelines to choose an appropriate experimental model.'''Beaudoin S, Barbet P, Bargy F.
Department of Pediatric Surgery, Groupe Hospitalier Cochin-Saint-Vincent de Paul, Paris, France. sylvie.beaudoine@svp.ap-hop-paris.fr

Researchers involved in the field of congenital malformations are often forced to work on an animal model. Both accurate description of its normal development and comparative staging with human development will be mandatory. To complete the lacking medical literature, we herein provide such data for the rabbit model. Sampled rabbit embryos were staged using the Carnegie criteria, in order first to determine if they were consistent with the rabbit developmental pattern, and second to compare this pattern with the human one. Our results show a suitable comparison of rabbits and humans in early developmental stages, except for the neural growth. Copyright 2003 S. Karger AG, Basel

2009 Group Project 1

2009-10-14T12:13:11Z

Z3185685: /* Introduction */

[[File:Rabbits.png|right|400 px]]

== '''THE RABBIT (ORYCTOLAGUS CUNICULUS)''' ==

==Introduction==

[[File:Isidro_Martinez.jpg‎|left|175 px]]

Several characteristics of the rabbit make it an excellent model for study. This will be further explored in "The History of Model Use" section of this page. Many studies have resulted in the development and improvement of various micro-manipulation techniques such as the production of transgenic rabbits. Unlike many other species such as the chick or rat, relatively little is known about the development of a rabbit. Nevertheless, it is still an appropriate animal model as the results from many experiments are significant to that of other mammals, including humans. (55)

A rabbits potential for reproduction is high, breeding from the early stages of 3 to 4 months of age. A mature female rabbit can be pregnant from 6 to 8 months in a year, producing up to 30 to 40 young in this time. (56)

==History of Model Use==

'''WHY are we using rabbits?'''

ADVANTAGES
*Provides repeatability of animal model studies
*Large enough for single samples
*Many stocks/strains as animal models
*Easily managed
*Quality of immunologic products
*Ease of reproductive control

DISADVANTAGES
*Most colonies are a storehouse of diseases
*Extremely variable to responses to general anesthetics

'''Brief timeline of rabbit embryo model use'''

*1672- de Graaf found the Graffian follicle.
*1890- Walter Heape succeeded first mammalian embryo transfer
*1906- FT Lewis discovered the development of the lymphatic system in rabbit embryos.
*1941- Dr. Pincus succeeded in keeping rabbit embryos developing in the test
*1968- Edwards and Gardner successfully performed the first known embryo biopsy on rabbit embryos

=== Regnier de Graaf (1641–1673) ===
[[image:Ovary_Graaf.jpg|thumb|250px|left|drawing of ovary]]
[[File:Regnier de Graaf.jpg|right]]

'''Discovery of the Graafian Follicles'''

In 1672 de Graaf published ''The Generative Organs of Women'', which was primarily a study of development in the rabbit. When de Graaf discovered large, round welling on the ovaries of rabbits, he assumed they were mammalian eggs. De Graaf also described the corpus luteum.

He summarised the previous works from anatomists, but unable to experience the amazing benefits made by microscopy.
But Antonie van Leeuwenhoek (A microbiologist, 1632 - 1723) argued that the structures now known as Graafian follicles could not be eggs. Haller suggested that the egg might be formed by the coagulation of the fluid within the Graafian follicle. De Graaf noted that the “egg” did not contain a tiny embryo, but he thought it did contain the “germ” of the future organism. (3)

=== Walter Heape (1855-1928) ===
'''First case of embryo transfer experiments'''

On 27 April 1890, Walter Heape (a professor and physician at the University of Cambridge, England) transferred rabbit embryos from one mother to another. (7) One rabbit mother became pregnant and delivered young from the transferred embryos. This was the first mammalian embryo transfer experiment to be successfully completed. His embryo transfer work in perspective as it relates to other contributions of this pioneer in reproductive biology.(7)

In 1891, Walter Heape had been conducting research on reproduction in numerous animal species. Working with two species of rabbits, he flushed embryos from the rabbit fallopian tubes of one breed (Angora) and placed them into the uterus of a recently mated Belgian hare. In the resulting litter, there were 4 Belgians and 2 Angoras. Heape proved that it was possible to take preimplantation embryos and transfer them to a gestational carrier without affecting their development.(7)

===Dr. Gregory Goodwin Pincus (1903-1967) ===

'''Contraceptive pill'''

Dr. Pincus began studying hormonal biology and steroidal hormones early in his career. His first breakthrough came when he was able to produce in vitro fertilization in rabbits (by using chemicals) in 1934. Throughout their hormonal contraceptive research Pincus, along with reproductive physiologist Min Chueh Chang, found out progesterone would act as an inhibitor to ovulation. They co-invented the combined oral contraceptive pill.[2][6]

===Genetic Diagnosis===
In 1968, Robert Edwards and David Gardner reported the successful sexing of rabbit blastocysts, setting the first steps towards PGD (Preimplantation Genetic Diagnosis). It was not until the 1980s that human IVF was fully developed, which coincided with the breakthrough of the highly sensitive polymerase chain reaction (PCR) technology. Handyside and collaborators' first successful attempts at testing were in October 1989 with the first births in 1990 though the preliminary experiments had been published some years earlier. In these first cases, PCR was used for sex determination for patients carrying X-linked diseases.(12)

==Timeline of Embryo Development==

The following is a timeline, adapted from Cibelli (2002), of the main events of preimplantation development in rabbits. The time is measured in hours post-mating and shows the embryo stage (cell number) in each time scale.

[[File:Morula1.JPG|right|200 px|thumb|A day 2 early morula]]

'''12-14 hours:''' Oocyte; Fertilization

'''18-20 hours:''' Zygote; Pronuclear formation

'''24-26 hours:''' Two cell

'''30-32 hours:''' Four cell

'''38-40 hours:''' Eight cell; Maternal-zygotic transition

'''46-48 hours:''' Sixteen cell

'''54-56 hours:''' Morula (32 cell); Compaction and transport to uterus

'''64-66 hours:''' Compact morula (64 cell); Morula-blastocyst transition

'''76-78 hours:''' Early blastocyst (128 cell)

'''84-86 hours:''' Expanded blastocyst (256 cell); Blastocoels expansion

'''94-96 hours:''' Hatched blastocyst (512 cell); Hatching

The following shows a diagrammatic representation of the relative sizes of rabbit embryos. The sizes do not include the embryonic coverings such as the zona pellucida and mucin coat. This diagram has been adapted from Warner (2003).

[[File:Sizes.JPG]]

The following timelines show a comparison of the developmental stages between human and rabbit embryos. They have been adapted from Derelanko (2008). "The similarities of this developmental pattern in humans and rabbits, suggests that the same growth increment is required to achieve the same stage. The main difference observed between human rabbit gestational duration is due to the fetal growth phase. The reason for this may be due to birth weight, lifetime and the neural complexity of the species." (59)

[[File:Timeline_rabbit.JPG]]

The following timelines have been adapted from a study carried out by Beaudoin et al. on the development of rabbit embryos.

==='''Body Form'''===

'''8.5 days''': Embryo thickens. First somites appear. Rostral neuropore closes. Caudal neuropore remains open

'''9.5 days''': Dorsal curvature begins. Cardiac mass bulges under cephalic pole.

'''10.5 - 13.5 days''': Dorsal curvature increases. Body thickens. Softening of the cephalic domination straightens the embryo.

'''17.5 days''': Neck becomes visible.

==='''Limb Development'''===

''' 9.5 days''': Rostral limb bud appears

'''10.5 days''': Caudal limb bud appears

'''12.5 days''': Hand plate becomes present. Limbs become disposed.

'''13.5 days''': Foot plate and finger rays become visible.

'''14.5 days''': Rostral and caudal limbs become parallel.

'''15.5 days''': Elbow appears.

'''16.5 days''': Fingers start to elongate.

'''17.5 days''': Knee becomes visible

'''19.5 days''': Hands and feet merge on the midline. Three segments of limbs become distinguished.

==='''Abdominal Wall Development'''===

'''9.5 days''': Abdominal wall is limited to the embryonic pedicle under the cardiac mass.

'''13.5 days''': First intestinal loops appear in the umbilical cord.

'''14.5 days – 17.5''': Rapid intestinal development in the cord.

'''15.5 days''': Abdominal vesicles can be observed.

'''16.5 days''': Cecal bud becomes present outside the abdomen

'''18.5 days''': Bowel returns to the abdominal cavity and umbilical ring closes.

==='''Cephalic Development'''===

'''9.5 days''': One cerebral vesicle can be seen. Pharyngeal arches as optic vesicle are present.

'''10.5 days''': Three arches are distinguished in the cephalic pole.

'''11.5 days''': Three cerebral vesicles present. Optic plate is distinguished.

'''12.5 days''': Face develops nasal, maxillar and mandibular buds. Lens vesicle is closed. Five cerebral vesicles exist.

'''14.5 days''': The ear becomes refined. Face can be distinguished from the brow.

'''18.5 days''': Eyelid appears, covering the eyes.

==Staging==

The following stages have been adapted from Beaudoin et al. (2003). Table 1 represents at each age its corresponding stage defined by the Carnegie classification

{| class="wikitable" style="text-align:center; width: 800px; height:1000px" border="1"
|+'''Table 1. Rabbit developmental stages using Carnegie classification'''

|- style="height:50px"
! '''Stage''' !! '''Days''' !! '''Event''' !! '''Image'''
|- style="width:200px"
! width="50" | 10
| width="50" | 8.5 || First somites appear, rostral neuropore closes
|- style="height:75px"
! 12
| 9.5 || Rostral limb bud, embryonic pedicle, caudal neuropore closes, one cerebral vesicle, pharyngeal arches, completion of optic vesicle
| [[file: 9.5new.JPG|100px]]
|- style="height:75px"
! 13
| 10.5 || Dosral C-shaped curvature, caudal limb bud, prominent cardiac swelling, four pharyngeal arches
| [[file: 10.5new.JPG|100px]]
|- style="height:75px"
! 14
| 11.5 || Three cerebral vesicles, optic plate, mesonephric ridge
|- style="height:75px"
! 15
| 12.5 || Hand plate, wheel ray limbs, lens vesicle closes, five cerebral vesicles, facial buds, vertebrae
| [[file: 12.5new.JPG|100px]]
|- style="height:75px"
! 16
| 13.5 || Foot plate, finger rays, prominent liver, intestinal loops, auricular hillocks
| [[file: 13.5new.JPG|100px]]
|- style="height:100px"
! 19
| 14.5 || Cuboidal body, trunk straightens, parallel limbs, toe rays, modeled face, visible auricle
| [[file: 14.5new.JPG|100px]]
|- style="height:75px"
! 20
| 15.5 || Elbow, fingers elongate, notches between toe rays
| [[file: 15.5new.JPG|100px]]
|- style="height:75px"
! 21-22
| 16.5 || Toes free, cecal bud in intestinal hernia
| [[file: 16.5new.JPG|100px]]
|- style="height:75px"
! 22-23
| 17.5 || Knee, neck, eyelids
| [[file: 17.5new.JPG|100px]]
|- style="height:75px"
! 23
| 18.5 || Hands and feet join at the midline, closure of abdominal wall, eyelids cover eyes
| [[file: 18.5new.JPG|100px]]
|-
| colspan="4" align="center"| Following this stage fetal appearance is completed, organogenesis is achieved
|}

==Genetics==

===Sequencing===
The National Human Genome Research Institute selected the European rabbit (Oryctolagus cuniculus) for whole genome sequencing to enhance their understanding of the human genome and use it experimentally for an animal model for human disease. (8)

The rabbit has been sequenced twice by The Broad Institute as part of the mammalian genome project. It is now currently undergoing 7 more sequencing projects. Its sequencing is made by the Whole Genome Shotgun (WGS) and assembly method. (9) This is when genomic DNA is sheared into small pieces of approximately 2000 base pairs which are then cloned into plasmids and sequenced on both strands. Once the contig fragments are read, realigned and reassembled by computer algorithms, it will give the overall sequence. (10) (11) The image below shows diagramatically how the two types of sequencing are different. The same techniques are used for sequencing the human genome (in 2003). [A contig is a set of overlapping DNA segments, derived from a single source of genetic material, from which the complete sequence may be deduced.

The whole genome shotgun (WGS) has serious gaps, yet the information has already proven useful for immunological as well as in silico studies. Deeper 7x coverage started in September 2007. The NCBI Rabbit Genome Resources site has links to searches for genes in the assemblies of the 2x WGS sequence at Ensembl and UCSC.(12) [http://www.broadinstitute.org/models/europeanrabbit/ Rabbit Genome Project]

[[File:WGS_sequencing.gif‎|center|800 px]]

===Genome===
The Rabbit genome was published by two groups (9)
# Lindblad-Toh,K., Chang,J.L., Gnerre,S., Clamp,M. and Lander,E.S. published their admission of 84024 bases on May 5th 2005 to The Broad Institute (USA) by shotgun sequencing
# Di Palma,F., Heiman,D., Young,S., Gnerre,S., Johnson,J., Lander,E.S. and Lindblad-Toh,K. published their admission of 84024 bases on August 3rd 2009 to The Broad Institute (USA) by shotgun sequencing.
The rabbit's genome is sequenced and on display in the Nucleotide Data Bank. It is too long to produce here. A link to the data bank is provided: [http://www.ncbi.nlm.nih.gov/nuccore/256946799/ Rabbit Genome from the Nucleotide Data Bank]

[[File:8cellembryo.jpg|thumb|Individual mitochondria (arrowheads) of an 8cell Rabbit embryo]]

The rabbit genome was sequenced in 2005 by Ensembl and managed to produce: (13)
* 2,076,044,328 supercontigs (ordered Contigs with gaps)
* 495 Known protein-coding genes
* 11,357 Projected protein-coding genes
* 2,343 RNA genes
* 212,581 Gene exons
* 20,311 Gene transcripts

For further research the taxonomy ID number for the Rabbit is: 9986 [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=9986&lvl=3&lin=f&keep=1&srchmode=1&unlock/ Taxonomy Data]

===Mitochondrial Genome===
The mitochondiral genome (mtDNA) of the rabbit was sequenced on November 14th 2006 with 17245 base pairs/nucleotides in circular form. Apparently the "length is not absolute due to the presence of different numbers of repeated motifs in the control region".
PMID 9653643

The image to the right shows the mitochondria during cell division and multiplication in embryo development.

=== Chromosomes ===
Over the years there have been various data suggesting the diploid chromosomal number for the rabbit may range from 22-42. However through recent research and an abundance of trials suggest that the rabbit does indeed have 22 different chromosome pairs existing in each cell of the rabbit. (16)(17) The sex chromosomes of the rabbit are of X-Y type convincingly (17). In a study in Bombay it confirmed that a rabbit has 2n = 44 chromosomes. There were 21 pairs of autosomes, out of which 1 to 6 were metacentric, 7 to 11 submetacentric, 12 to 17 subtelocentric and 18 to 21 acrocentric, plus the sex chromosomes. The image to the left shows a female rabbit with no chromosomal abnormalities. (19)

'''Comparison to human chromosome:'''

Rabbit chromosomes 12, 19 and X were found to be completely homologous to human chromosomes 6, 17 and X, respectively. All other human chromosomes were homologous to two or sometimes three rabbit chromosomes. (14) Chromosome 12 was shorter than chromosomes 13 and 14. (15) The image below illustrates the human chromosome (2n = 46).

[[File:Drawn chromosome.jpg|left|400 px]]

[[File:Karyotypehuman.gif|right|500 px]]

'''Abnormalities'''

These are generally more apparent during early embryo development in blastocysts from delayed fertilization. Some examples of abnormal development include cases of: (18)
* hypoploidy; 1 chromosome missing from a pair (2n = 43),
* double hypoploidy; 2 chromosomes missing from 2 different pairs (2n = 42),
* mosaicism (different chromosomal makeup in some cells).

Another study also found these abnormalities as well as: (19)
* autosomal trisomy (3 autosomes per pair),
* triploidy (extra set of chromsomes),
* mixoploidy (unequal number of chromosome sets in adjacent cells), and
* short arm deletion (deletion of parts of chromosomes).

A specific abnormality occurring in rabbits is the x-linked tremor. There is a mutation in exon 2 of the prteolipid-protein (PLP 1) gene, corresponding to the end of the first potential transmembrane domain of the protein. This disorder affects myelination of the central nervous system. OMIA ID:12 [http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=full_report&list_uids=100009169&log$=omiamaingene| Gene:100009169]

==Abnormal Development==

Abnormal embryological development is a vast field of study that has been the subject of recent research papers. Our investigation of abnormal development in rabbit embryology will focus on abnormalities commonly found in both rabbit and human embryos. We will explore the nature of these abnormalities in both humans and rabbits.

[[File:Normal v Abnormal.jpg|right|300 px|thumb|Brain MRI of patient with Hydrocephalus (left) compared to a normal brain (right). An obvious increase in ventricular size and a significant decrease in brain size is present.]]
[[File:Ventricle_Expansion.jpg|right|300 px|thumb|CSF accumulation in ventricles of brain increasing intracranial pressure.The pressure from the expanding ventricles force the brain and skull to grow outwards abnormally.]]

'''Hydrocephalus'''

Annually, one in every 1000 children born in Australia have hydrocephalus. Hydrocephalus occurs when excessive cerebrospinal fluid (CSF) accumulates in the brain and can result in severe disability and even death because the disorder can result in complete or near complete destruction of the cerebral cortex (22).

Children born with hydrocephalus typically exhibit abnormally large head circumference and bulging cranial fontanels as a result of increased intracranial pressure on the brain from the accumulating CSF (22,23). As CSF accumulates in the ventricles and CSF compartments of the brain, it expands forcing the brain to grow outward. The outward growing brain places pressure on the skull which in turn also grows outwards giving rise to an abnormally large head circumference and bulging cranial fontanels (22,24). It is generally acknowledged that children with hydrocephalus have mental retardation, often to the degree of being “vegetative” (24).

The serious consequences of this disease mean that much research is necessary to unearth methods of prevention and effective treatment. One of the modes of studying hydrocephalus is to use the rabbit experimental model where hydrocephalus can be induced in rabbit embryo’s. The injection of silicone oil into the cisterna magna of the brain is one way of inducing hydrocephalus in the rabbit embryo. The silicone oil obstructs the normal flow of CSF resulting in CSF accumulation in the brain leading to hydrocephalus (25). Another method of inducing hydrocephalus in rabbit embryo’s is by intentional vitamin A deprivation of pregnant dams. The vitamin A deficiency results in raised intracranial CSF pressure and aqueduct stenosis causing poor circulation of CSF leading to hydrocephalus (26,27). Although the exact function of vitamin A on brain development and CSF regulation is not fully understood, it is clear that Vitamin A has an important role in brain development and its normal functioning (27).
[[File:Rabbithhdrocephalus.jpg|center|300 px|thumb|Young rabbit with hydrocephalus caused by Vitamin A deficiency. Note the abnormally shaped cranium inflamed in appearance.]]

[[File:SpinabifidaMeningocele1.jpg|right|300 px|thumb|Spina Bifida Meningocele has characteristic damage to the meninges of the spinal cord which are pushed out through an opening in the vertebrae as a cyst filled with CSF.]]
[[File:SpinaBifidaMyelomeningocele.jpg|right|300 px|thumb|Spina Bifida Myelomeningocele is the most severe form of spinabifida where the damaged spinal cord protrudes out with damaged meninges as a cyst filled with CSF.]]
[[File:SpinaBifidaOcculta1.jpg|right|300 px|thumb|Spina Bifida Occulta is the least severe as the spinal cord and meninges are undamaged.]]

'''Spina Bifida'''

In Australia, the risk of spina bifida is 1 in every 500 pregnancies. Spina bifida is a type of neural tube defect where vertebrae (which normally cover and protect the spinal cord) are not completely formed but are divided resulting in the defective spinal cord and its coverings to protrude through the opening (28,29).

There are three main types of Spina Bifida differentiated by their characteristic features:

1)Spina Bifida Meningocele characterized by normal spinal cord, divided outer vertebrae and meninges surrounding the spinal cord protruding from the divided vertebrae as a cyst (1,28).

2)Spina Bifida Myelomeningocele characterized by split outer vertebrae with spinal cord and its meninges protruding from the divided vertebrae as a cyst. Commonly found at lumbar vertebral level (1,28,29).

3)Spina Bifida Occulta characterized unfused vertebral arches and exposed vertebral canal. Spinal cord and its meninges still located in vertebral canal (1,28).

All forms of spina bifida are potentially fatal and in those where the spinal cord is damaged severe consequence arise including and paralysis and loss of sensation at and below the level of damage spinal cord damage (29,33). There is a lot of Spina bifida research using rabbit models to test the effective methods of correcting spina bifida. The occurrence of natural spina bifida in rabbits is rare and for experimental purposes it can be surgically created in rabbit fetuses during gestation (31,32). The process involves aesthetical sedation of the maternal rabbit at day 22 of gestation; a midline laparotomy performed and the desired type of spina bifida lesion created on the exposed fetus using forceps. Different methods for correcting spina bifida can then be tested and its effectiveness analysed (30,33,34).
[[File:Rabbitspinabifida1.jpg|center|350 px|thumb|Rabbit newborn with Spina Bifida. Note the unfused, divided vertebrae and exposed spinal cord.]]

'''Brachydactylia & Acheiropodia'''

[[File:Malformation1.jpg|right|150 px|thumb|Acheiropodia in rabbit characterized by amputations of the limbs and extremities.]]

[[File:Rabbitmalformation3.jpg|left|150 px|thumb|X-Ray study of rabbit limbs with malformed phalanges due to Brachydactylia.]]

Brachydactylia and Acheiropodia are genetic disorders characterized by skeletal malformation of the hands and feet (36,36). In Brachydactylia, the malformations commonly involve abnormal shortening of fingers and toes due to poorly formed or absent bones (35). Acheiropodia is characterized by more severe skeletal malformations including bilateral amputations of the distal upper and lower extremities as well as aplasia of the hands and feet. Although it is not fatal, the individual endures a very difficult life without hands and feet (37).

The inheritance mechanism of this diseases can has been studied through experiment using rabbits. Rabbits with abnormal genes coding for Brachydactylia and Acheiropodia are selected and bred to produce offspring with the disease (36). Brachydactylia and Acheiropodia are autosomal recessive disorders which means that two copies of an abnormal gene must be present in the affected individual in order for the disease to develop. Thus, each parent passes an abnormal gene to the offspring (35,36). The process of the malformation progresses from genotype to phenotype; small deletions on the chromosomes produce abnormal genes, the abnormal genes are then passed down to the offspring, the offspring that inherits two of the abnormal genes is unable to code for the correct proteins and as a result, there is failure in normal development of limb extremities in the embryo phenotype (37,38).

==Current Embryology Research==

There is currently great excitement in research involving rabbits in the fields of transgenesis, cloning and stem cells. We shall explore research in these areas by discovering some of the techniques used and how they have been applied to the rabbit model.

[[File:Trans1.jpg|right|170 px]]
[[File:Trans2.jpg|right|170 px]]
[[File:Trans3.jpg|right|170 px]]
[[File:Trans4.jpg|right|170 px]]
[[File:Trans5.jpg|right|170 px]]

'''Transgenic rabbit'''

A transgenic organism is one whose genome also contains genes from another species (39). The aim of creating a transgenic organism is to obtain a favorable characteristic in the organism’s phenotype (41). This desired characteristic of phenotype is obtained by altering the organism’s normal genotype to include the gene from another species with the desired characteristic (39,40).

The production of a transgenic organism involves several steps summarized below:

1) The chromosome and the desired gene on it are identified in an organism (39).

2) The gene is isolated from its DNA strand. This involves “cutting” it out of its DNA strand using enzymes called restriction endonucleases. The restriction endonucleases cut DNA at specific site so the desired gene can be removed from the DNA strand. The cut ends are known as “sticky ends” (39,40).

3) Separate DNA sequences for regulation sometimes have to be added to ensure the gene will work (40).

4) The gene is then inserted with a promoter sequence into the fertilized egg cell of a new organism producing recombinant DNA (39,44). To do this, firstly the new organism’s cell DNA must first be cut and the desired gene incorporated into it. The same enzymes are used to cut the new organism’s cell DNA because the DNA stands from the two different organisms will form matching sticky ends that will be attracted to and connect with each other in a process is called “annealing” (39,40,44).

5) DNA ligases are sealing enzymes found in all living organisms that help make and repair DNA (39,40). The DNA ligases are added to the annealed DNA fragments to help strengthen the bonds of the new recombinant DNA. The recombinant DNA is now transferred into the new organism’s fertilized egg by microinjection (44).

6) As the embryo develops and the recombinant genetic code read, new proteins are synthesized which code for the new desired phenotype characteristic in the transgenic organism (39,40).

Transgenic rabbits can be created in the laboratory by gene microinjection into the fertilized rabbit oocyte (44). In April 2000, a transgenic rabbit named Alba was born containing a gene from a Pacific Northwest jellyfish. The gene which was injected into a fertilized albino rabbit oocyte allows the rabbit to synthesize the green fluorescent protein (GFP) that is characteristic of the Pacific Northwest jellyfish. When illuminated correctly, Alba glows a bright green (43,46).

Transgenic rabbits have important research purposes. Transgenic rabbits can be created to model retinal degeneration (44). Retinal degeneration is a common problem with aging and diseases such as diabetes, and frequently leads to complete blindness (42). A genetic retinal degeneration disease called retinitis pigmentosa (RP) is created in these rabbits by introducing the “Pro347Leu” mutation of the rhodopsin gene into fertilized rabbit eggs (43,44). As the rabbit grows, it develops the disease which becomes progressively worse (45).
The use of these transgenic rabbits ultimately leads to better understanding of the disease and more effective treatments (42). [[File:Transgenic rabbit.jpg|center|250 px|thumb|"Alba" A trangenic rabbit with a gene from a Pacific Northwest jellyfish that allows it to synthesize the green fluorescent protein (GFP) of the jellyfish.]]

[[File:Crabbit 1.jpg|right|170 px]]
[[File:Rabbit2.jpg|right|170 px]]
[[File:Rabbit3.jpg|right|170 px]]
[[File:Crabbit 4.jpg|right|170 px]]

'''Cloning'''

Cloning is a method of producing genetically identical organisms. The principle of cloning relies on “tricking” an egg cell to begin rapidly dividing into an embryo (39). In the normal fertilization process, two haploid sex cells unite to form a diploid zygote which begins rapidly dividing into an embryo (40). By replacing the haploid egg cell nucleus with a diploid somatic cell nucleus, the egg cell is tricked into thinking it is fertilized and hence begins rapidly dividing to form an embryo (39,40,41).

The process of cloning involves several steps summarized as the following using a rabbit example:

1) A somatic cell is obtained from a rabbit and the nucleus removed (39).

2) An egg cell is obtained from a donor rabbit and the nucleus of the egg cell removed using an enucleation needle. The cell is now called an enucleated egg cell (egg cell without a nucleus) (39,41).

3) The nucleus of the somatic cell is inserted into the enucleated egg cell (41).

4) The cell is now stimulated to divide by applying pulses of electric current (39).

5) The rapidly dividing cell develops in culture for a few days forming the early embryo (40,41).

6) The embryo is then implanted into the uterus of another rabbit similar to the egg cell donor. This rabbit is called the surrogate mother (40,41).

7) The embryo develops and the surrogate mother gives birth to a rabbit fetus with near identical genotype of the somatic cell donor (the small genomic difference is caused by the fetus obtaining mitochondrial DNA from the egg cell donor) (39,41).

The cloning of rabbits has been achieved by inserting the diploid nucleus of a rabbit fibroblast (the principal cells in connective tissue) into an enucleated oocyte (49). There is currently much focus on the creation of controversial but revolutionary interspecies hybrid embryos where the nucleus from a human somatic cells are implanted into an enucleated egg cell of another animal (50). The resulting embryo (known as a chimera) will be almost completely human genotype but will have genome from the other animal (48). In 2003, scientists at the Shanghai Second Medical University fused human cell with rabbit eggs creating the first human-rabbit hybrid using the nucleus transfer technique. The hybrid embryo developed in culture for a few days before it was destroyed and the stem cells harvested (47,48). The purpose of the research into creating hybrid embryos is to provide researchers with human stem cells for experimentation into cures for diseases such as cystic fibrosis, Alzheimer’s and Motor Neuron disease as human stem cell are difficult to obtain (50).

[[File:Rabbit clone.jpg|center|450 px|thumb|(A) Cloned rabbits (5 month old) from nuclear transfer technique. (B) The male rabbit whose fibroblasts were used as the nuclear donors. The cloned rabbits have almost identical genome to the male donor.]]

'''Stem Cells'''
[[File:HES.jpg|right|200 px|thumb|Human Embryonic Stem cell (hES).]]
[[File:Rabbit knee.jpg|right|200 px|thumb|Stem cell induced cartilage repair of knee in rabbit.]]

Stem cells are unspecialized cells which are able to continuously reproduce themselves and under appropriate conditions, differentiate into all the various specialized cells of the organism such as cardiac cells, neurons and blood cells (39,40). Adults have a small number of stem cells when compared to a developing embryo and the stem cell of an embryo more easily obtained (41). Human embryonic stem cells (hES) derived from the inner mass of the preimplantation blastocyst have the potential to differentiate into all cell types in the human body and thus are valued by researchers (50). However, due to ethical and political issues, the obtaining and experimentation on human embryonic stem cells is difficult and alternate means are needed as stem cell provides potentially new treatments for a range of diseases (54).

Rabbits can be used both in the obtaining of stem cell for experimentation and also as recipients of stem cells to cure diseases. The human-rabbit hybrid embryo provides a method of obtaining stem cells for experimentation and these stem cells possess many similar properties to human stem cells, including expression of surface markers, special growth requirements, capabilities of self renewal, formation of embryonic body and differentiation into cells of all three germ layers (53).

Stem cell experimentation on rabbits also focuses on transplanting stem cell into rabbits to treat specific diseases. A study at Zhejiang University where a research team transplanted human mesenchymal stem cell into New Zealand white rabbits with myocardial infarction recoded regeneration of vascular structure and improvement in cardiac function. The research team noted the potential of stem cells in differentiating into specialized cardiac cells when subjected to the specific conditions of the rabbit heart (52).

Another study at Hallym University tested the effectiveness of transplanting mesenchymal stem cells from New Zealand white rabbits into damaged cartilage in the knees of other New Zealand white rabbits. In the experiment, mesenchymal stem cells were obtained from the rabbit bone marrow and injected into the knees of other rabbits that had cartilage in their knees surgically damaged. The research team were able to conclude notable cartilage recovery in the rabbits with the mesenchymal stem cell injection and the potential of mesenchymal stem cells to differentiate into fibroblasts, adipoblasts, osteoblasts and chondroblasts (51,53).

The findings in stem cell experimentation with in rabbits yielded positive results and potentially opens a new field of research in the use of stem cell to treat a range of diseases in humans.

==References==

# Dr Mark Hill 2009, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G [6]
# E.Horne Craigie, University of Toronto Press 1948, Bensley's Practical Anatomy of the Rabbit 8th Edition
# Ankum WM, Houtzager HL, Bleker OP (1996). "Reinier De Graaf (1641-1673) and the fallopian tube". Human Reproduction Update 2 (4): 365–9. doi:10.1093/humupd/2.4.365. PMID 9080233.
# Jocelyn HD, Setchell BP (December 1972). "Regnier de Graaf on the human reproductive organs. An annotated translation of Tractatus de Virorum Organis Generationi Inservientibus (1668) and De Mulierub Organis Generationi Inservientibus Tractatus Novus (1962)". Journal of Reproduction and Fertility. Supplement 17: 1–222.
# Jay, V. (2000). "A portrait in history. The legacy of Reinier de Graaf". Archives of Pathology & Laboratory Medicine 124(8): 1115–6.
# Lois N Magner. "A history of the Life Sciences" 3rd edition
# J. D. Biggers. (1991). Walter Heape, FRS: a pioneer in reproductive biology.Centenary of his embryo transfer experiments Laboratory of Human Reproduction and Reproductive Biology, and Department of Cellular and Molecular Physiology, Harvard Medical School, Boston, MA 02115, USA
# National Center for Biotechnology Information. (June 16, 2009). ''Rabbit Genome Resources'', Retrieved August 20, 2009, from [http://www.ncbi.nlm.nih.gov/projects/genome/guide/rabbit/ NCBI Rabbit Genome Site]
# The Broad Institute. (2008). ''Rabbit Genome Sequencing Project''. Retrieved only August 29, 2009, from [http://www.broadinstitute.org/models/europeanrabbit/ Rabbit Genome Sequencing Project]
# Campbell, M. A. (2002). ''Sequencing Whole Genomes: Hierarchical Shotgun Sequencing v. Shotgun Sequencing'' Retrieved August 31, 2009, from [http://www.bio.davidson.edu/courses/GENOMICS/method/shotgun.html/ Shotgun Sequencing - 1]
# Trivedi, B. (2000). ''Sequencing the Genome''. Retrieved September 4, 2009, from [http://www.genomenewsnetwork.org/articles/06_00/sequence_primer.shtml Shotgun Sequencing - 2]
# Mage, R. (2008). Rabbit genome sequencing update: genes of immunological interest found in the 2x genome assemblies, ENCODE, and the 7x trace archive. ''Journal of FASEB'' 22(Retrieved September 5, 2009, from [http://www.fasebj.org/cgi/content/meeting_abstract/22/2_MeetingAbstracts/559/ Rabbit Genome & its Immunological Interest]
# Ensembl (2009). ''Rabbit (Oryctolagus cuniculus)''. Retrieved September 5, 2009, from [http://www.ensembl.org/Oryctolagus_cuniculus/Info/Index/ Ensembl Genome Project]
# Korstanje, R. et al. (1999) Complete homology maps of the rabbit (Oryctolagus cuniculus) and human by reciprocal chromosome painting. ''Cytogenetics and cell genetics'' ''86''(3-4), 317-322. Retrieved September 6, 2009, from [http://cat.inist.fr/?aModele=afficheN&cpsidt=1189693/ Complete homology maps of the rabbit Article] "PMID 10575232"
# Brunner, R., Knopp, A., Rudolph, W. (n.d). Rabbit chromosome analysis by image processing. ''Journal of Applied Rabbit Research''.
# DebMark Rabbit Education Resource (2006). ''Rabbit Genetics''. Retrieved September 6, 2009, from [http://www.debmark.com/rabbits/genetics.htm/ Rabbit Genetics]
# Painter, T. (2009) Studies in mammalian spermatogenesis VI. The chromosomes of the rabbit. ''Journal of Morphology''. ''43''(1): 1-43.
# Hofsaess, F., and Meacham, T. ( 1995) Chromosome abnormalities of early rabbit embryos. ''Journal of Experimental Zoology''. ''177'' (1): 9-11 [http://www3.interscience.wiley.com/journal/110490865/abstract/ Chromosome abnormalities]
# Martin-Deleon, P., Shaver, E., and Gammal, E. (1973) Chromosome abnormalities in rabbit blastocysts resulting from spermatozoa aged in the male tract. ''Fertility and Sterility''. ''24''(3):212-219.
# Patil, M. et al (2004) Chromosome analysis of domestic rabbit. ''The Journal of Bombay Veterinary College''. ''12'' (1 and 2)
#Biggers J.D (1991) Walter Heape FRS: a pioneer in reproductive biology. centenary of his embryo transfer experments.''Journals of reproduction and fertility''. ''93''(1)
# Stoodley, M (2006). Hydrocephalus. Prince of Wales Clinical School. Retrieved from [http://www.brainaustralia.org.au/AZ_of_Brain_Disorders/hydrocephalus]
# National Institute of Neurological Disorders and Stroke (2008, February). Hydrocephalus Fact Sheet. Retrieved from [http://www.ninds.nih.gov/disorders/hydrocephalus/detail_hydrocephalus.htm]
# Lewin, R (1999). Is Your Brain Really Necessary?. 24) Developmental Medicine & Child Neurology, 41. Retrieved from [http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=176431]
# Bigio, M.R, & Bruni J.E (1991). Silicone oil-induced hydrocephalus in the rabbit . Child's Nervous System, 7(2), Retrieved from [http://www.springerlink.com/content/b011477724837152/]
# Geelen, J.A (1974). A case of hydrocephalus and meningoencephalocele in a rabbit, caused by aqueductal malformation. Laboratory Animals, 8(2), Retrieved from [http://la.rsmjournals.com/cgi/content/abstract/8/2/167]
# LAMMINGX, G.E (1954). 27) Hydrocephalus in Young Rabbits Associated with Maternal Vitamin A Deficiency. British Journal of Nutrition, 8(2), Retrieved from [http://journals.cambridge.org/download.php?file=%2FBJN%2FBJN8_04%2FS0007114554000554a.pdf&code=10bb1dbc4a9e57a091f4e05f6aebbcf2]
# Carney, A (2008, February ). Spina bifida. Retrieved from [http://www.spinabifida.asn.au/]
# Better Health Channel (2008, October ). Spina bifida explained . Retrieved from [http://www.betterhealth.vic.gov.au/bhcv2/bhcarticles.nsf/pages/Spina_bifida_explained]
# Peeters, M.C, Viebahn, C, & Hekking, J.W (1998). Neurulation in the rabbit embryo . Anatomy and Embryology, 197(3), Retrieved from [http://www.springerlink.com/content/1efyteewgetjlwyg/]
# George, T.M, & Fuh E (2003). Review of Animal Models of Surgically Induced Spinal Neural Tube Defects: Implications for fetal surgery. Pediatric Neurosurgery , 39(2), Retrieved from [http://content.karger.com/produktedb/produkte.asp?typ=fulltext&file=PNE2003039002081]
# Pedreira, D.A, & Valente P.R (2002). A Different Technique to Create a 'Myelomeningocele-Like' Defect in the Fetal Rabbit. Fetal diagnosis and therapy, 17(6), Retrieved from [http://content.karger.com/ProdukteDB/produkte.asp?Doi=65388]
# Patten, B.M (1953). Embryological stages in the establishing of myeloschisis with spina bifida. The American journal of anatomy, 93(3), Retrieved from [http://deepblue.lib.umich.edu/handle/2027.42/49611]
# Pedreira, D.A, & Valente P.R (2003). Successful Fetal Surgery for the Repair of a 'Myelomeningocele-Like' Defect Created in the Fetal Rabbit. Fetal Diagnosis and Therapy, 18. Retrieved from [http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowPDF&ProduktNr=224239&Ausgabe=229041&ArtikelNr=69378]
# Lecklitner, M.L, & Douglas K.P (1986). Osteoscintigraphy and brachydactylia of the hand . European Journal of Nuclear Medicine and Molecular Imaging, 12(9), Retrieved from [http://www.springerlink.com/content/t82l77282x579102/]
# Greene, H.S, & Saxton J.A (1938). HEREDITARY BRACHYDACTYLIA AND ALLIED. ABNORMALITIES IN THE RABBIT. THE JOURNAL OF EXPERIMENTAL MEDICINE , 69. Retrieved from [http://jem.rupress.org/cgi/reprint/69/2/301.pdf]
# P. Ianakiev, M. van Baren, M. Daly, S. Toledo, M. Cavalcanti, J. Neto, E. Silveira, A. Freire-Maia, P. Heutink, M. Kilpatrick. Acheiropodia Is Caused by a Genomic Deletion in C7orf2, the Human Orthologue of the Lmbr1 Gene. The American Journal of Human Genetics, 68. Retrieved from [http://linkinghub.elsevier.com/retrieve/pii/S0002929707624707]
# Walbaum, R, Hazard, C, & Cordier, R (1976). Brachydactylia with symphalangism, probably autosomal recessive . Human Genetics, 33(2), Retrieved from [http://www.springerlink.com/content/m630p6880661486n]
# Campbell, N.A, & Reece, J.B (2002). Biology 6th Edition. USA: Benjamin Cummings.
# Solomon, E.P, Berg, L.R, & Martin, D.W (2002). Biology 6th Edition. USA: Thompson Learning.
# Glanville, A.R (2008). Scientifica. NSW, Australia: Millennium House.
# Lund, R.D (2008). Saving Vision with Skin Cells. Retrieved from [http://www.blindness.org]
# Jones, B.W, & Marc R.E (2008). Computational Molecular Phenotyping and Excitation Mapping in the P347L. Retinal Degeneration , (2986), Retrieved from [http://prometheus.med.utah.edu/]
# Kondo, M, Sakai, T, & Ueno, S (2009). Generation of a Transgenic Rabbit Model of Retinal Degeneration. Investigative Ophthalmology and Visual Science, 50. Retrieved from [http://www.iovs.org/cgi]
# Punzo, C, Chen, B, & Roesch, K (2009). PHOTORECEPTOR DEATH IN MOUSE MODELS OF RETINITIS PIGMENTOSA. Retrieved from [http://genepath.med.harvard.edu]
# Zimmer, M (2008). Alba. Retrieved from [http://www.conncoll.edu/ccacad/zimmer/GFP-ww/cooluses8.html]
# Scott, C (2006, May 1). Chimeras in the crosshairs. Nature Biotechnology , 24, Retrieved from [http://www.nature.com/nbt/journal/v24/n5/abs/nbt0506-487.html]
# Mott, M (2005, January 25). Animal-Human Hybrids Spark Controversy. National Geographic News, Retrieved from [http://theyfly.com/PDF/Nat.%20Geo.%20Animal-Human%20Hybrids.pdf]
# Li, S, & Chen X (2006). Rabbits generated from fibroblasts through nuclear transfer . Society for Reproduction and Fertility, 131. Retrieved from [http://www.reproduction-online.org/cgi/reprint/131/6/1085]
# Minger, S (2007). Interspecies SCNT derived human embryos. Regenerative Medicine, 2(2), Retrieved from [http://www.futuremedicine.com]
# Koga, H, Shimaya, M, & Muneta, T (2008). Local adherent technique for transplanting mesenchymal stem cells as a potential treatment of cartilage defect. Arthritis Research & Therapy, 10(4), Retrieved from [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2575632]
# Wang, J, Li, C, & Sun, Y (2005). Human bone marrow-derived mesenchymal stem cells transplanted into damaged rabbit heart to improve heart function. Journal of Zhejiang University Science, 6(4), Retrieved from [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1389731]
# Chen, Y, Liu, A, & Mao, W (2003). Embryonic stem cells generated by nuclear transfer of human somatic nuclei into rabbit oocytes. Cell Research , 13(4), Retrieved from [http://www.nature.com]
# Bethesda (2009, September 23). Stem Cell Information. Retrieved from [http://stemcells.nih.gov]
# Cibelli, J. B. (2002). Principles of cloning Amsterdam. Academic Press
# European rabbit (oryctolagus cuniculus) Retrieved 9/21/2009, 2009, from http://www.feral.org.au/content/species/rabbit.cfm
# Warner, S. (2003). Inositol transport in preimplantation rabbit embryos: Effects of embryo stage, sodium, osmolality and metabolic inhibitors Reproduction, 125(4), 479-493.
# Derelanko, M. J. (2008). The toxicologist's pocket handbook, second edition Informa HealthCare
# Beaudoin, S., Barbet, P., & Bargy, F. (2003). Developmental stages in the rabbit embryo: Guidelines to choose an appropriate experimental model Fetal Diagnosis and Therapy, 18(6), 422-427.

==Glossary==

Anesthetic - A drug that causes temporary loss of bodily sensations

Aplasia - The absence or defective development of a tissue or organ

Blastocyst - A stage of embryo development that occurs about five days after fertilisation when the embryo contains quite a few cells

Caudal - Situated towards the inferior or posterior end of the body

Cephalic - Relating to the head

Cerebral Aqueduct - A canal filled with cerebrospinal fluid within the midbrain

Cerebral Cortex - The layer of unmyelinated neurons (the grey matter) forming the cortex of the cerebrum of the brain

Cerebro Spinal Fluid (CSF) - A watery fluid which flows in the cavities within the brain and around the surface of the brain and spinal cord

Chromosome - Microscopic carriers of genetic material, composed of deoxyribonucleic acid (DNA) and proteins and appearing as rods under a microscope

Cisterna Magna - is one of three principal openings in the subarachnoid space between the arachnoid and pia mater layers of the meninges surrounding the brain

Diploid - A full set of genetic material, consisting of paired chromosomes one chromosome from each parental set

Dorsal - Position towards the back

Fontanel - Membranous gap between the bones of the cranium in an infant or fetus

Genome - All genetic information, the entire genetic complement and all of the hereditary material possessed by an organism. Made up of both chromosomal genome (inside the nucleus of the cell in the familiar form of chromosomes) and mitochondrial genome (outside the nucleus in the cytoplasm of the cell, usually in the form of one round chromosome (the mitochondrial chromosome))

Genotype - The genetic makeup of an organism

Glucocorticoids - A class of steroid hormones that bind to the glucocorticoid receptor (GR), which is present in almost every vertebrate

Haploid - A single set of chromosomes (half the full set of genetic material)

Laparotomy- Surgical incision into the abdominal wall; often done to examine abdominal organs

Ligases - Group of enzymes that catalyze the binding of two molecules

Oocyte - A female gametocyte that develops into an ovum after two meiotic divisions

Phenotype - The observable traits or characteristics of an organism, for example hair color, weight, or the presence or absence of a disease.

Pronuclear - Haploid nucleus before fusion of nuclei in fertilisation

Restriction Endonucleases - Enzymes that recognize and cleave specific DNA sequences, generating either blunt or single-stranded (sticky) ends

Retina - The thin layer of cells at the back of the eyeball where light is converted into neural signals sent to the brain

Rostral - Situated toward the oral and nasal region

Somite - Blocks of mesoderm on either side of the notochord and neural tube during development of the vertebrate embryo. Develop into muscles and vertebrae

Stenosis - Abnormal narrowing of a bodily canal or passageway

Weaning - Young become accustom to nourishment other than suckling

==Links to Research Laboratories and Researchers==

1) Transgenic lab: [http://www.dnavision.be/index.php]

Involved in development of transgenic organisms, DNA construction and phenotype analysis.

2) World Rabbit Science Association: (WRSA) [http://world-rabbit-science.com]

International Association where researchers exchange knowledge and encourage teaching, scientific research, practical experimentation, the collection and publication of statistics and documents relating to the rabbit. Even have their own journal called “World Rabbit Science”

Website provides contact with researchers, professors and veterinarians working with rabbits.

Example: Dr. Myriam Kaplan-Pasternak, Doctorate Veterinary Medicine, University of California, myriamsemail@gmail.com

3) American Veterinary Medical Association [http://www.avma.org]

The American Veterinary Medical Association (AVMA), established in 1863, is a not-for-profit association representing more than 78,000 veterinarians working in private and corporate practice, government, industry, academia, and uniformed services. Excellent website into animal research and has a range of veterinary journals.

{{Template:Projects09}}
[[Category:Rabbit]]
[[File:Example.jpg]]

2009 Group Project 1

2009-10-14T12:11:37Z

Z3185685: /* Introduction */

[[File:Rabbits.png|right|400 px]]

== '''THE RABBIT (ORYCTOLAGUS CUNICULUS)''' ==

==Introduction==

[[File:Isidro_Martinez.jpg‎|left|175 px]]

Several characteristics of the rabbit make it an excellent model for study. This will be further explored in "The History of Model Use" section of this page. Many studies have resulted in the development and improvement of various micro-manipulation techniques such as the production of transgenic rabbits. Unlike many other species such as the chick or rat, relatively little is known about the development of a rabbit. Nevertheless, the rabbit is still an appropriate animal model as the results from many experiments are significant to that of other mammals, including humans. (55)

A rabbits potential for reproduction is high, breeding from the early stages of 3 to 4 months of age. A mature female rabbit can be pregnant from 6 to 8 months in a year, producing up to 30 to 40 young in this time. (56)

==History of Model Use==

'''WHY are we using rabbits?'''

ADVANTAGES
*Provides repeatability of animal model studies
*Large enough for single samples
*Many stocks/strains as animal models
*Easily managed
*Quality of immunologic products
*Ease of reproductive control

DISADVANTAGES
*Most colonies are a storehouse of diseases
*Extremely variable to responses to general anesthetics

'''Brief timeline of rabbit embryo model use'''

*1672- de Graaf found the Graffian follicle.
*1890- Walter Heape succeeded first mammalian embryo transfer
*1906- FT Lewis discovered the development of the lymphatic system in rabbit embryos.
*1941- Dr. Pincus succeeded in keeping rabbit embryos developing in the test
*1968- Edwards and Gardner successfully performed the first known embryo biopsy on rabbit embryos

=== Regnier de Graaf (1641–1673) ===
[[image:Ovary_Graaf.jpg|thumb|250px|left|drawing of ovary]]
[[File:Regnier de Graaf.jpg|right]]

'''Discovery of the Graafian Follicles'''

In 1672 de Graaf published ''The Generative Organs of Women'', which was primarily a study of development in the rabbit. When de Graaf discovered large, round welling on the ovaries of rabbits, he assumed they were mammalian eggs. De Graaf also described the corpus luteum.

He summarised the previous works from anatomists, but unable to experience the amazing benefits made by microscopy.
But Antonie van Leeuwenhoek (A microbiologist, 1632 - 1723) argued that the structures now known as Graafian follicles could not be eggs. Haller suggested that the egg might be formed by the coagulation of the fluid within the Graafian follicle. De Graaf noted that the “egg” did not contain a tiny embryo, but he thought it did contain the “germ” of the future organism. (3)

=== Walter Heape (1855-1928) ===
'''First case of embryo transfer experiments'''

On 27 April 1890, Walter Heape (a professor and physician at the University of Cambridge, England) transferred rabbit embryos from one mother to another. (7) One rabbit mother became pregnant and delivered young from the transferred embryos. This was the first mammalian embryo transfer experiment to be successfully completed. His embryo transfer work in perspective as it relates to other contributions of this pioneer in reproductive biology.(7)

In 1891, Walter Heape had been conducting research on reproduction in numerous animal species. Working with two species of rabbits, he flushed embryos from the rabbit fallopian tubes of one breed (Angora) and placed them into the uterus of a recently mated Belgian hare. In the resulting litter, there were 4 Belgians and 2 Angoras. Heape proved that it was possible to take preimplantation embryos and transfer them to a gestational carrier without affecting their development.(7)

===Dr. Gregory Goodwin Pincus (1903-1967) ===

'''Contraceptive pill'''

Dr. Pincus began studying hormonal biology and steroidal hormones early in his career. His first breakthrough came when he was able to produce in vitro fertilization in rabbits (by using chemicals) in 1934. Throughout their hormonal contraceptive research Pincus, along with reproductive physiologist Min Chueh Chang, found out progesterone would act as an inhibitor to ovulation. They co-invented the combined oral contraceptive pill.[2][6]

===Genetic Diagnosis===
In 1968, Robert Edwards and David Gardner reported the successful sexing of rabbit blastocysts, setting the first steps towards PGD (Preimplantation Genetic Diagnosis). It was not until the 1980s that human IVF was fully developed, which coincided with the breakthrough of the highly sensitive polymerase chain reaction (PCR) technology. Handyside and collaborators' first successful attempts at testing were in October 1989 with the first births in 1990 though the preliminary experiments had been published some years earlier. In these first cases, PCR was used for sex determination for patients carrying X-linked diseases.(12)

==Timeline of Embryo Development==

The following is a timeline, adapted from Cibelli (2002), of the main events of preimplantation development in rabbits. The time is measured in hours post-mating and shows the embryo stage (cell number) in each time scale.

[[File:Morula1.JPG|right|200 px|thumb|A day 2 early morula]]

'''12-14 hours:''' Oocyte; Fertilization

'''18-20 hours:''' Zygote; Pronuclear formation

'''24-26 hours:''' Two cell

'''30-32 hours:''' Four cell

'''38-40 hours:''' Eight cell; Maternal-zygotic transition

'''46-48 hours:''' Sixteen cell

'''54-56 hours:''' Morula (32 cell); Compaction and transport to uterus

'''64-66 hours:''' Compact morula (64 cell); Morula-blastocyst transition

'''76-78 hours:''' Early blastocyst (128 cell)

'''84-86 hours:''' Expanded blastocyst (256 cell); Blastocoels expansion

'''94-96 hours:''' Hatched blastocyst (512 cell); Hatching

The following shows a diagrammatic representation of the relative sizes of rabbit embryos. The sizes do not include the embryonic coverings such as the zona pellucida and mucin coat. This diagram has been adapted from Warner (2003).

[[File:Sizes.JPG]]

The following timelines show a comparison of the developmental stages between human and rabbit embryos. They have been adapted from Derelanko (2008). "The similarities of this developmental pattern in humans and rabbits, suggests that the same growth increment is required to achieve the same stage. The main difference observed between human rabbit gestational duration is due to the fetal growth phase. The reason for this may be due to birth weight, lifetime and the neural complexity of the species." (59)

[[File:Timeline_rabbit.JPG]]

The following timelines have been adapted from a study carried out by Beaudoin et al. on the development of rabbit embryos.

==='''Body Form'''===

'''8.5 days''': Embryo thickens. First somites appear. Rostral neuropore closes. Caudal neuropore remains open

'''9.5 days''': Dorsal curvature begins. Cardiac mass bulges under cephalic pole.

'''10.5 - 13.5 days''': Dorsal curvature increases. Body thickens. Softening of the cephalic domination straightens the embryo.

'''17.5 days''': Neck becomes visible.

==='''Limb Development'''===

''' 9.5 days''': Rostral limb bud appears

'''10.5 days''': Caudal limb bud appears

'''12.5 days''': Hand plate becomes present. Limbs become disposed.

'''13.5 days''': Foot plate and finger rays become visible.

'''14.5 days''': Rostral and caudal limbs become parallel.

'''15.5 days''': Elbow appears.

'''16.5 days''': Fingers start to elongate.

'''17.5 days''': Knee becomes visible

'''19.5 days''': Hands and feet merge on the midline. Three segments of limbs become distinguished.

==='''Abdominal Wall Development'''===

'''9.5 days''': Abdominal wall is limited to the embryonic pedicle under the cardiac mass.

'''13.5 days''': First intestinal loops appear in the umbilical cord.

'''14.5 days – 17.5''': Rapid intestinal development in the cord.

'''15.5 days''': Abdominal vesicles can be observed.

'''16.5 days''': Cecal bud becomes present outside the abdomen

'''18.5 days''': Bowel returns to the abdominal cavity and umbilical ring closes.

==='''Cephalic Development'''===

'''9.5 days''': One cerebral vesicle can be seen. Pharyngeal arches as optic vesicle are present.

'''10.5 days''': Three arches are distinguished in the cephalic pole.

'''11.5 days''': Three cerebral vesicles present. Optic plate is distinguished.

'''12.5 days''': Face develops nasal, maxillar and mandibular buds. Lens vesicle is closed. Five cerebral vesicles exist.

'''14.5 days''': The ear becomes refined. Face can be distinguished from the brow.

'''18.5 days''': Eyelid appears, covering the eyes.

==Staging==

The following stages have been adapted from Beaudoin et al. (2003). Table 1 represents at each age its corresponding stage defined by the Carnegie classification

{| class="wikitable" style="text-align:center; width: 800px; height:1000px" border="1"
|+'''Table 1. Rabbit developmental stages using Carnegie classification'''

|- style="height:50px"
! '''Stage''' !! '''Days''' !! '''Event''' !! '''Image'''
|- style="width:200px"
! width="50" | 10
| width="50" | 8.5 || First somites appear, rostral neuropore closes
|- style="height:75px"
! 12
| 9.5 || Rostral limb bud, embryonic pedicle, caudal neuropore closes, one cerebral vesicle, pharyngeal arches, completion of optic vesicle
| [[file: 9.5new.JPG|100px]]
|- style="height:75px"
! 13
| 10.5 || Dosral C-shaped curvature, caudal limb bud, prominent cardiac swelling, four pharyngeal arches
| [[file: 10.5new.JPG|100px]]
|- style="height:75px"
! 14
| 11.5 || Three cerebral vesicles, optic plate, mesonephric ridge
|- style="height:75px"
! 15
| 12.5 || Hand plate, wheel ray limbs, lens vesicle closes, five cerebral vesicles, facial buds, vertebrae
| [[file: 12.5new.JPG|100px]]
|- style="height:75px"
! 16
| 13.5 || Foot plate, finger rays, prominent liver, intestinal loops, auricular hillocks
| [[file: 13.5new.JPG|100px]]
|- style="height:100px"
! 19
| 14.5 || Cuboidal body, trunk straightens, parallel limbs, toe rays, modeled face, visible auricle
| [[file: 14.5new.JPG|100px]]
|- style="height:75px"
! 20
| 15.5 || Elbow, fingers elongate, notches between toe rays
| [[file: 15.5new.JPG|100px]]
|- style="height:75px"
! 21-22
| 16.5 || Toes free, cecal bud in intestinal hernia
| [[file: 16.5new.JPG|100px]]
|- style="height:75px"
! 22-23
| 17.5 || Knee, neck, eyelids
| [[file: 17.5new.JPG|100px]]
|- style="height:75px"
! 23
| 18.5 || Hands and feet join at the midline, closure of abdominal wall, eyelids cover eyes
| [[file: 18.5new.JPG|100px]]
|-
| colspan="4" align="center"| Following this stage fetal appearance is completed, organogenesis is achieved
|}

==Genetics==

===Sequencing===
The National Human Genome Research Institute selected the European rabbit (Oryctolagus cuniculus) for whole genome sequencing to enhance their understanding of the human genome and use it experimentally for an animal model for human disease. (8)

The rabbit has been sequenced twice by The Broad Institute as part of the mammalian genome project. It is now currently undergoing 7 more sequencing projects. Its sequencing is made by the Whole Genome Shotgun (WGS) and assembly method. (9) This is when genomic DNA is sheared into small pieces of approximately 2000 base pairs which are then cloned into plasmids and sequenced on both strands. Once the contig fragments are read, realigned and reassembled by computer algorithms, it will give the overall sequence. (10) (11) The image below shows diagramatically how the two types of sequencing are different. The same techniques are used for sequencing the human genome (in 2003). [A contig is a set of overlapping DNA segments, derived from a single source of genetic material, from which the complete sequence may be deduced.

The whole genome shotgun (WGS) has serious gaps, yet the information has already proven useful for immunological as well as in silico studies. Deeper 7x coverage started in September 2007. The NCBI Rabbit Genome Resources site has links to searches for genes in the assemblies of the 2x WGS sequence at Ensembl and UCSC.(12) [http://www.broadinstitute.org/models/europeanrabbit/ Rabbit Genome Project]

[[File:WGS_sequencing.gif‎|center|800 px]]

===Genome===
The Rabbit genome was published by two groups (9)
# Lindblad-Toh,K., Chang,J.L., Gnerre,S., Clamp,M. and Lander,E.S. published their admission of 84024 bases on May 5th 2005 to The Broad Institute (USA) by shotgun sequencing
# Di Palma,F., Heiman,D., Young,S., Gnerre,S., Johnson,J., Lander,E.S. and Lindblad-Toh,K. published their admission of 84024 bases on August 3rd 2009 to The Broad Institute (USA) by shotgun sequencing.
The rabbit's genome is sequenced and on display in the Nucleotide Data Bank. It is too long to produce here. A link to the data bank is provided: [http://www.ncbi.nlm.nih.gov/nuccore/256946799/ Rabbit Genome from the Nucleotide Data Bank]

[[File:8cellembryo.jpg|thumb|Individual mitochondria (arrowheads) of an 8cell Rabbit embryo]]

The rabbit genome was sequenced in 2005 by Ensembl and managed to produce: (13)
* 2,076,044,328 supercontigs (ordered Contigs with gaps)
* 495 Known protein-coding genes
* 11,357 Projected protein-coding genes
* 2,343 RNA genes
* 212,581 Gene exons
* 20,311 Gene transcripts

For further research the taxonomy ID number for the Rabbit is: 9986 [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=9986&lvl=3&lin=f&keep=1&srchmode=1&unlock/ Taxonomy Data]

===Mitochondrial Genome===
The mitochondiral genome (mtDNA) of the rabbit was sequenced on November 14th 2006 with 17245 base pairs/nucleotides in circular form. Apparently the "length is not absolute due to the presence of different numbers of repeated motifs in the control region".
PMID 9653643

The image to the right shows the mitochondria during cell division and multiplication in embryo development.

=== Chromosomes ===
Over the years there have been various data suggesting the diploid chromosomal number for the rabbit may range from 22-42. However through recent research and an abundance of trials suggest that the rabbit does indeed have 22 different chromosome pairs existing in each cell of the rabbit. (16)(17) The sex chromosomes of the rabbit are of X-Y type convincingly (17). In a study in Bombay it confirmed that a rabbit has 2n = 44 chromosomes. There were 21 pairs of autosomes, out of which 1 to 6 were metacentric, 7 to 11 submetacentric, 12 to 17 subtelocentric and 18 to 21 acrocentric, plus the sex chromosomes. The image to the left shows a female rabbit with no chromosomal abnormalities. (19)

'''Comparison to human chromosome:'''

Rabbit chromosomes 12, 19 and X were found to be completely homologous to human chromosomes 6, 17 and X, respectively. All other human chromosomes were homologous to two or sometimes three rabbit chromosomes. (14) Chromosome 12 was shorter than chromosomes 13 and 14. (15) The image below illustrates the human chromosome (2n = 46).

[[File:Drawn chromosome.jpg|left|400 px]]

[[File:Karyotypehuman.gif|right|500 px]]

'''Abnormalities'''

These are generally more apparent during early embryo development in blastocysts from delayed fertilization. Some examples of abnormal development include cases of: (18)
* hypoploidy; 1 chromosome missing from a pair (2n = 43),
* double hypoploidy; 2 chromosomes missing from 2 different pairs (2n = 42),
* mosaicism (different chromosomal makeup in some cells).

Another study also found these abnormalities as well as: (19)
* autosomal trisomy (3 autosomes per pair),
* triploidy (extra set of chromsomes),
* mixoploidy (unequal number of chromosome sets in adjacent cells), and
* short arm deletion (deletion of parts of chromosomes).

A specific abnormality occurring in rabbits is the x-linked tremor. There is a mutation in exon 2 of the prteolipid-protein (PLP 1) gene, corresponding to the end of the first potential transmembrane domain of the protein. This disorder affects myelination of the central nervous system. OMIA ID:12 [http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=full_report&list_uids=100009169&log$=omiamaingene| Gene:100009169]

==Abnormal Development==

Abnormal embryological development is a vast field of study that has been the subject of recent research papers. Our investigation of abnormal development in rabbit embryology will focus on abnormalities commonly found in both rabbit and human embryos. We will explore the nature of these abnormalities in both humans and rabbits.

[[File:Normal v Abnormal.jpg|right|300 px|thumb|Brain MRI of patient with Hydrocephalus (left) compared to a normal brain (right). An obvious increase in ventricular size and a significant decrease in brain size is present.]]
[[File:Ventricle_Expansion.jpg|right|300 px|thumb|CSF accumulation in ventricles of brain increasing intracranial pressure.The pressure from the expanding ventricles force the brain and skull to grow outwards abnormally.]]

'''Hydrocephalus'''

Annually, one in every 1000 children born in Australia have hydrocephalus. Hydrocephalus occurs when excessive cerebrospinal fluid (CSF) accumulates in the brain and can result in severe disability and even death because the disorder can result in complete or near complete destruction of the cerebral cortex (22).

Children born with hydrocephalus typically exhibit abnormally large head circumference and bulging cranial fontanels as a result of increased intracranial pressure on the brain from the accumulating CSF (22,23). As CSF accumulates in the ventricles and CSF compartments of the brain, it expands forcing the brain to grow outward. The outward growing brain places pressure on the skull which in turn also grows outwards giving rise to an abnormally large head circumference and bulging cranial fontanels (22,24). It is generally acknowledged that children with hydrocephalus have mental retardation, often to the degree of being “vegetative” (24).

The serious consequences of this disease mean that much research is necessary to unearth methods of prevention and effective treatment. One of the modes of studying hydrocephalus is to use the rabbit experimental model where hydrocephalus can be induced in rabbit embryo’s. The injection of silicone oil into the cisterna magna of the brain is one way of inducing hydrocephalus in the rabbit embryo. The silicone oil obstructs the normal flow of CSF resulting in CSF accumulation in the brain leading to hydrocephalus (25). Another method of inducing hydrocephalus in rabbit embryo’s is by intentional vitamin A deprivation of pregnant dams. The vitamin A deficiency results in raised intracranial CSF pressure and aqueduct stenosis causing poor circulation of CSF leading to hydrocephalus (26,27). Although the exact function of vitamin A on brain development and CSF regulation is not fully understood, it is clear that Vitamin A has an important role in brain development and its normal functioning (27).
[[File:Rabbithhdrocephalus.jpg|center|300 px|thumb|Young rabbit with hydrocephalus caused by Vitamin A deficiency. Note the abnormally shaped cranium inflamed in appearance.]]

[[File:SpinabifidaMeningocele1.jpg|right|300 px|thumb|Spina Bifida Meningocele has characteristic damage to the meninges of the spinal cord which are pushed out through an opening in the vertebrae as a cyst filled with CSF.]]
[[File:SpinaBifidaMyelomeningocele.jpg|right|300 px|thumb|Spina Bifida Myelomeningocele is the most severe form of spinabifida where the damaged spinal cord protrudes out with damaged meninges as a cyst filled with CSF.]]
[[File:SpinaBifidaOcculta1.jpg|right|300 px|thumb|Spina Bifida Occulta is the least severe as the spinal cord and meninges are undamaged.]]

'''Spina Bifida'''

In Australia, the risk of spina bifida is 1 in every 500 pregnancies. Spina bifida is a type of neural tube defect where vertebrae (which normally cover and protect the spinal cord) are not completely formed but are divided resulting in the defective spinal cord and its coverings to protrude through the opening (28,29).

There are three main types of Spina Bifida differentiated by their characteristic features:

1)Spina Bifida Meningocele characterized by normal spinal cord, divided outer vertebrae and meninges surrounding the spinal cord protruding from the divided vertebrae as a cyst (1,28).

2)Spina Bifida Myelomeningocele characterized by split outer vertebrae with spinal cord and its meninges protruding from the divided vertebrae as a cyst. Commonly found at lumbar vertebral level (1,28,29).

3)Spina Bifida Occulta characterized unfused vertebral arches and exposed vertebral canal. Spinal cord and its meninges still located in vertebral canal (1,28).

All forms of spina bifida are potentially fatal and in those where the spinal cord is damaged severe consequence arise including and paralysis and loss of sensation at and below the level of damage spinal cord damage (29,33). There is a lot of Spina bifida research using rabbit models to test the effective methods of correcting spina bifida. The occurrence of natural spina bifida in rabbits is rare and for experimental purposes it can be surgically created in rabbit fetuses during gestation (31,32). The process involves aesthetical sedation of the maternal rabbit at day 22 of gestation; a midline laparotomy performed and the desired type of spina bifida lesion created on the exposed fetus using forceps. Different methods for correcting spina bifida can then be tested and its effectiveness analysed (30,33,34).
[[File:Rabbitspinabifida1.jpg|center|350 px|thumb|Rabbit newborn with Spina Bifida. Note the unfused, divided vertebrae and exposed spinal cord.]]

'''Brachydactylia & Acheiropodia'''

[[File:Malformation1.jpg|right|150 px|thumb|Acheiropodia in rabbit characterized by amputations of the limbs and extremities.]]

[[File:Rabbitmalformation3.jpg|left|150 px|thumb|X-Ray study of rabbit limbs with malformed phalanges due to Brachydactylia.]]

Brachydactylia and Acheiropodia are genetic disorders characterized by skeletal malformation of the hands and feet (36,36). In Brachydactylia, the malformations commonly involve abnormal shortening of fingers and toes due to poorly formed or absent bones (35). Acheiropodia is characterized by more severe skeletal malformations including bilateral amputations of the distal upper and lower extremities as well as aplasia of the hands and feet. Although it is not fatal, the individual endures a very difficult life without hands and feet (37).

The inheritance mechanism of this diseases can has been studied through experiment using rabbits. Rabbits with abnormal genes coding for Brachydactylia and Acheiropodia are selected and bred to produce offspring with the disease (36). Brachydactylia and Acheiropodia are autosomal recessive disorders which means that two copies of an abnormal gene must be present in the affected individual in order for the disease to develop. Thus, each parent passes an abnormal gene to the offspring (35,36). The process of the malformation progresses from genotype to phenotype; small deletions on the chromosomes produce abnormal genes, the abnormal genes are then passed down to the offspring, the offspring that inherits two of the abnormal genes is unable to code for the correct proteins and as a result, there is failure in normal development of limb extremities in the embryo phenotype (37,38).

==Current Embryology Research==

There is currently great excitement in research involving rabbits in the fields of transgenesis, cloning and stem cells. We shall explore research in these areas by discovering some of the techniques used and how they have been applied to the rabbit model.

[[File:Trans1.jpg|right|170 px]]
[[File:Trans2.jpg|right|170 px]]
[[File:Trans3.jpg|right|170 px]]
[[File:Trans4.jpg|right|170 px]]
[[File:Trans5.jpg|right|170 px]]

'''Transgenic rabbit'''

A transgenic organism is one whose genome also contains genes from another species (39). The aim of creating a transgenic organism is to obtain a favorable characteristic in the organism’s phenotype (41). This desired characteristic of phenotype is obtained by altering the organism’s normal genotype to include the gene from another species with the desired characteristic (39,40).

The production of a transgenic organism involves several steps summarized below:

1) The chromosome and the desired gene on it are identified in an organism (39).

2) The gene is isolated from its DNA strand. This involves “cutting” it out of its DNA strand using enzymes called restriction endonucleases. The restriction endonucleases cut DNA at specific site so the desired gene can be removed from the DNA strand. The cut ends are known as “sticky ends” (39,40).

3) Separate DNA sequences for regulation sometimes have to be added to ensure the gene will work (40).

4) The gene is then inserted with a promoter sequence into the fertilized egg cell of a new organism producing recombinant DNA (39,44). To do this, firstly the new organism’s cell DNA must first be cut and the desired gene incorporated into it. The same enzymes are used to cut the new organism’s cell DNA because the DNA stands from the two different organisms will form matching sticky ends that will be attracted to and connect with each other in a process is called “annealing” (39,40,44).

5) DNA ligases are sealing enzymes found in all living organisms that help make and repair DNA (39,40). The DNA ligases are added to the annealed DNA fragments to help strengthen the bonds of the new recombinant DNA. The recombinant DNA is now transferred into the new organism’s fertilized egg by microinjection (44).

6) As the embryo develops and the recombinant genetic code read, new proteins are synthesized which code for the new desired phenotype characteristic in the transgenic organism (39,40).

Transgenic rabbits can be created in the laboratory by gene microinjection into the fertilized rabbit oocyte (44). In April 2000, a transgenic rabbit named Alba was born containing a gene from a Pacific Northwest jellyfish. The gene which was injected into a fertilized albino rabbit oocyte allows the rabbit to synthesize the green fluorescent protein (GFP) that is characteristic of the Pacific Northwest jellyfish. When illuminated correctly, Alba glows a bright green (43,46).

Transgenic rabbits have important research purposes. Transgenic rabbits can be created to model retinal degeneration (44). Retinal degeneration is a common problem with aging and diseases such as diabetes, and frequently leads to complete blindness (42). A genetic retinal degeneration disease called retinitis pigmentosa (RP) is created in these rabbits by introducing the “Pro347Leu” mutation of the rhodopsin gene into fertilized rabbit eggs (43,44). As the rabbit grows, it develops the disease which becomes progressively worse (45).
The use of these transgenic rabbits ultimately leads to better understanding of the disease and more effective treatments (42). [[File:Transgenic rabbit.jpg|center|250 px|thumb|"Alba" A trangenic rabbit with a gene from a Pacific Northwest jellyfish that allows it to synthesize the green fluorescent protein (GFP) of the jellyfish.]]

[[File:Crabbit 1.jpg|right|170 px]]
[[File:Rabbit2.jpg|right|170 px]]
[[File:Rabbit3.jpg|right|170 px]]
[[File:Crabbit 4.jpg|right|170 px]]

'''Cloning'''

Cloning is a method of producing genetically identical organisms. The principle of cloning relies on “tricking” an egg cell to begin rapidly dividing into an embryo (39). In the normal fertilization process, two haploid sex cells unite to form a diploid zygote which begins rapidly dividing into an embryo (40). By replacing the haploid egg cell nucleus with a diploid somatic cell nucleus, the egg cell is tricked into thinking it is fertilized and hence begins rapidly dividing to form an embryo (39,40,41).

The process of cloning involves several steps summarized as the following using a rabbit example:

1) A somatic cell is obtained from a rabbit and the nucleus removed (39).

2) An egg cell is obtained from a donor rabbit and the nucleus of the egg cell removed using an enucleation needle. The cell is now called an enucleated egg cell (egg cell without a nucleus) (39,41).

3) The nucleus of the somatic cell is inserted into the enucleated egg cell (41).

4) The cell is now stimulated to divide by applying pulses of electric current (39).

5) The rapidly dividing cell develops in culture for a few days forming the early embryo (40,41).

6) The embryo is then implanted into the uterus of another rabbit similar to the egg cell donor. This rabbit is called the surrogate mother (40,41).

7) The embryo develops and the surrogate mother gives birth to a rabbit fetus with near identical genotype of the somatic cell donor (the small genomic difference is caused by the fetus obtaining mitochondrial DNA from the egg cell donor) (39,41).

The cloning of rabbits has been achieved by inserting the diploid nucleus of a rabbit fibroblast (the principal cells in connective tissue) into an enucleated oocyte (49). There is currently much focus on the creation of controversial but revolutionary interspecies hybrid embryos where the nucleus from a human somatic cells are implanted into an enucleated egg cell of another animal (50). The resulting embryo (known as a chimera) will be almost completely human genotype but will have genome from the other animal (48). In 2003, scientists at the Shanghai Second Medical University fused human cell with rabbit eggs creating the first human-rabbit hybrid using the nucleus transfer technique. The hybrid embryo developed in culture for a few days before it was destroyed and the stem cells harvested (47,48). The purpose of the research into creating hybrid embryos is to provide researchers with human stem cells for experimentation into cures for diseases such as cystic fibrosis, Alzheimer’s and Motor Neuron disease as human stem cell are difficult to obtain (50).

[[File:Rabbit clone.jpg|center|450 px|thumb|(A) Cloned rabbits (5 month old) from nuclear transfer technique. (B) The male rabbit whose fibroblasts were used as the nuclear donors. The cloned rabbits have almost identical genome to the male donor.]]

'''Stem Cells'''
[[File:HES.jpg|right|200 px|thumb|Human Embryonic Stem cell (hES).]]
[[File:Rabbit knee.jpg|right|200 px|thumb|Stem cell induced cartilage repair of knee in rabbit.]]

Stem cells are unspecialized cells which are able to continuously reproduce themselves and under appropriate conditions, differentiate into all the various specialized cells of the organism such as cardiac cells, neurons and blood cells (39,40). Adults have a small number of stem cells when compared to a developing embryo and the stem cell of an embryo more easily obtained (41). Human embryonic stem cells (hES) derived from the inner mass of the preimplantation blastocyst have the potential to differentiate into all cell types in the human body and thus are valued by researchers (50). However, due to ethical and political issues, the obtaining and experimentation on human embryonic stem cells is difficult and alternate means are needed as stem cell provides potentially new treatments for a range of diseases (54).

Rabbits can be used both in the obtaining of stem cell for experimentation and also as recipients of stem cells to cure diseases. The human-rabbit hybrid embryo provides a method of obtaining stem cells for experimentation and these stem cells possess many similar properties to human stem cells, including expression of surface markers, special growth requirements, capabilities of self renewal, formation of embryonic body and differentiation into cells of all three germ layers (53).

Stem cell experimentation on rabbits also focuses on transplanting stem cell into rabbits to treat specific diseases. A study at Zhejiang University where a research team transplanted human mesenchymal stem cell into New Zealand white rabbits with myocardial infarction recoded regeneration of vascular structure and improvement in cardiac function. The research team noted the potential of stem cells in differentiating into specialized cardiac cells when subjected to the specific conditions of the rabbit heart (52).

Another study at Hallym University tested the effectiveness of transplanting mesenchymal stem cells from New Zealand white rabbits into damaged cartilage in the knees of other New Zealand white rabbits. In the experiment, mesenchymal stem cells were obtained from the rabbit bone marrow and injected into the knees of other rabbits that had cartilage in their knees surgically damaged. The research team were able to conclude notable cartilage recovery in the rabbits with the mesenchymal stem cell injection and the potential of mesenchymal stem cells to differentiate into fibroblasts, adipoblasts, osteoblasts and chondroblasts (51,53).

The findings in stem cell experimentation with in rabbits yielded positive results and potentially opens a new field of research in the use of stem cell to treat a range of diseases in humans.

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==Glossary==

Anesthetic - A drug that causes temporary loss of bodily sensations

Aplasia - The absence or defective development of a tissue or organ

Blastocyst - A stage of embryo development that occurs about five days after fertilisation when the embryo contains quite a few cells

Caudal - Situated towards the inferior or posterior end of the body

Cephalic - Relating to the head

Cerebral Aqueduct - A canal filled with cerebrospinal fluid within the midbrain

Cerebral Cortex - The layer of unmyelinated neurons (the grey matter) forming the cortex of the cerebrum of the brain

Cerebro Spinal Fluid (CSF) - A watery fluid which flows in the cavities within the brain and around the surface of the brain and spinal cord

Chromosome - Microscopic carriers of genetic material, composed of deoxyribonucleic acid (DNA) and proteins and appearing as rods under a microscope

Cisterna Magna - is one of three principal openings in the subarachnoid space between the arachnoid and pia mater layers of the meninges surrounding the brain

Diploid - A full set of genetic material, consisting of paired chromosomes one chromosome from each parental set

Dorsal - Position towards the back

Fontanel - Membranous gap between the bones of the cranium in an infant or fetus

Genome - All genetic information, the entire genetic complement and all of the hereditary material possessed by an organism. Made up of both chromosomal genome (inside the nucleus of the cell in the familiar form of chromosomes) and mitochondrial genome (outside the nucleus in the cytoplasm of the cell, usually in the form of one round chromosome (the mitochondrial chromosome))

Genotype - The genetic makeup of an organism

Glucocorticoids - A class of steroid hormones that bind to the glucocorticoid receptor (GR), which is present in almost every vertebrate

Haploid - A single set of chromosomes (half the full set of genetic material)

Laparotomy- Surgical incision into the abdominal wall; often done to examine abdominal organs

Ligases - Group of enzymes that catalyze the binding of two molecules

Oocyte - A female gametocyte that develops into an ovum after two meiotic divisions

Phenotype - The observable traits or characteristics of an organism, for example hair color, weight, or the presence or absence of a disease.

Pronuclear - Haploid nucleus before fusion of nuclei in fertilisation

Restriction Endonucleases - Enzymes that recognize and cleave specific DNA sequences, generating either blunt or single-stranded (sticky) ends

Retina - The thin layer of cells at the back of the eyeball where light is converted into neural signals sent to the brain

Rostral - Situated toward the oral and nasal region

Somite - Blocks of mesoderm on either side of the notochord and neural tube during development of the vertebrate embryo. Develop into muscles and vertebrae

Stenosis - Abnormal narrowing of a bodily canal or passageway

Weaning - Young become accustom to nourishment other than suckling

==Links to Research Laboratories and Researchers==

1) Transgenic lab: [http://www.dnavision.be/index.php]

Involved in development of transgenic organisms, DNA construction and phenotype analysis.

2) World Rabbit Science Association: (WRSA) [http://world-rabbit-science.com]

International Association where researchers exchange knowledge and encourage teaching, scientific research, practical experimentation, the collection and publication of statistics and documents relating to the rabbit. Even have their own journal called “World Rabbit Science”

Website provides contact with researchers, professors and veterinarians working with rabbits.

Example: Dr. Myriam Kaplan-Pasternak, Doctorate Veterinary Medicine, University of California, myriamsemail@gmail.com

3) American Veterinary Medical Association [http://www.avma.org]

The American Veterinary Medical Association (AVMA), established in 1863, is a not-for-profit association representing more than 78,000 veterinarians working in private and corporate practice, government, industry, academia, and uniformed services. Excellent website into animal research and has a range of veterinary journals.

{{Template:Projects09}}
[[Category:Rabbit]]
[[File:Example.jpg]]

2009 Group Project 1

2009-10-14T12:10:53Z

Z3185685: /* Introduction */

[[File:Rabbits.png|right|400 px]]

== '''THE RABBIT (ORYCTOLAGUS CUNICULUS)''' ==

==Introduction==

[[File:Isidro_Martinez.jpg‎|left|175 px]]

Several characteristics of the rabbit make it an excellent model for study. This will be further explored in "The History of Model Use" section of this page. Many studies have resulted in the development and improvement of various micro-manipulation techniques such as the production of transgenic rabbits. Unlike many other species such as the chick or rat, relatively little is known about the development of a rabbit, however, it is still an appropriate animal model as the results from many experiments are significant to that of other mammals, including humans. (55)

A rabbits potential for reproduction is high, breeding from the early stages of 3 to 4 months of age. A mature female rabbit can be pregnant from 6 to 8 months in a year, producing up to 30 to 40 young in this time. (56)

==History of Model Use==

'''WHY are we using rabbits?'''

ADVANTAGES
*Provides repeatability of animal model studies
*Large enough for single samples
*Many stocks/strains as animal models
*Easily managed
*Quality of immunologic products
*Ease of reproductive control

DISADVANTAGES
*Most colonies are a storehouse of diseases
*Extremely variable to responses to general anesthetics

'''Brief timeline of rabbit embryo model use'''

*1672- de Graaf found the Graffian follicle.
*1890- Walter Heape succeeded first mammalian embryo transfer
*1906- FT Lewis discovered the development of the lymphatic system in rabbit embryos.
*1941- Dr. Pincus succeeded in keeping rabbit embryos developing in the test
*1968- Edwards and Gardner successfully performed the first known embryo biopsy on rabbit embryos

=== Regnier de Graaf (1641–1673) ===
[[image:Ovary_Graaf.jpg|thumb|250px|left|drawing of ovary]]
[[File:Regnier de Graaf.jpg|right]]

'''Discovery of the Graafian Follicles'''

In 1672 de Graaf published ''The Generative Organs of Women'', which was primarily a study of development in the rabbit. When de Graaf discovered large, round welling on the ovaries of rabbits, he assumed they were mammalian eggs. De Graaf also described the corpus luteum.

He summarised the previous works from anatomists, but unable to experience the amazing benefits made by microscopy.
But Antonie van Leeuwenhoek (A microbiologist, 1632 - 1723) argued that the structures now known as Graafian follicles could not be eggs. Haller suggested that the egg might be formed by the coagulation of the fluid within the Graafian follicle. De Graaf noted that the “egg” did not contain a tiny embryo, but he thought it did contain the “germ” of the future organism. (3)

=== Walter Heape (1855-1928) ===
'''First case of embryo transfer experiments'''

On 27 April 1890, Walter Heape (a professor and physician at the University of Cambridge, England) transferred rabbit embryos from one mother to another. (7) One rabbit mother became pregnant and delivered young from the transferred embryos. This was the first mammalian embryo transfer experiment to be successfully completed. His embryo transfer work in perspective as it relates to other contributions of this pioneer in reproductive biology.(7)

In 1891, Walter Heape had been conducting research on reproduction in numerous animal species. Working with two species of rabbits, he flushed embryos from the rabbit fallopian tubes of one breed (Angora) and placed them into the uterus of a recently mated Belgian hare. In the resulting litter, there were 4 Belgians and 2 Angoras. Heape proved that it was possible to take preimplantation embryos and transfer them to a gestational carrier without affecting their development.(7)

===Dr. Gregory Goodwin Pincus (1903-1967) ===

'''Contraceptive pill'''

Dr. Pincus began studying hormonal biology and steroidal hormones early in his career. His first breakthrough came when he was able to produce in vitro fertilization in rabbits (by using chemicals) in 1934. Throughout their hormonal contraceptive research Pincus, along with reproductive physiologist Min Chueh Chang, found out progesterone would act as an inhibitor to ovulation. They co-invented the combined oral contraceptive pill.[2][6]

===Genetic Diagnosis===
In 1968, Robert Edwards and David Gardner reported the successful sexing of rabbit blastocysts, setting the first steps towards PGD (Preimplantation Genetic Diagnosis). It was not until the 1980s that human IVF was fully developed, which coincided with the breakthrough of the highly sensitive polymerase chain reaction (PCR) technology. Handyside and collaborators' first successful attempts at testing were in October 1989 with the first births in 1990 though the preliminary experiments had been published some years earlier. In these first cases, PCR was used for sex determination for patients carrying X-linked diseases.(12)

==Timeline of Embryo Development==

The following is a timeline, adapted from Cibelli (2002), of the main events of preimplantation development in rabbits. The time is measured in hours post-mating and shows the embryo stage (cell number) in each time scale.

[[File:Morula1.JPG|right|200 px|thumb|A day 2 early morula]]

'''12-14 hours:''' Oocyte; Fertilization

'''18-20 hours:''' Zygote; Pronuclear formation

'''24-26 hours:''' Two cell

'''30-32 hours:''' Four cell

'''38-40 hours:''' Eight cell; Maternal-zygotic transition

'''46-48 hours:''' Sixteen cell

'''54-56 hours:''' Morula (32 cell); Compaction and transport to uterus

'''64-66 hours:''' Compact morula (64 cell); Morula-blastocyst transition

'''76-78 hours:''' Early blastocyst (128 cell)

'''84-86 hours:''' Expanded blastocyst (256 cell); Blastocoels expansion

'''94-96 hours:''' Hatched blastocyst (512 cell); Hatching

The following shows a diagrammatic representation of the relative sizes of rabbit embryos. The sizes do not include the embryonic coverings such as the zona pellucida and mucin coat. This diagram has been adapted from Warner (2003).

[[File:Sizes.JPG]]

The following timelines show a comparison of the developmental stages between human and rabbit embryos. They have been adapted from Derelanko (2008). "The similarities of this developmental pattern in humans and rabbits, suggests that the same growth increment is required to achieve the same stage. The main difference observed between human rabbit gestational duration is due to the fetal growth phase. The reason for this may be due to birth weight, lifetime and the neural complexity of the species." (59)

[[File:Timeline_rabbit.JPG]]

The following timelines have been adapted from a study carried out by Beaudoin et al. on the development of rabbit embryos.

==='''Body Form'''===

'''8.5 days''': Embryo thickens. First somites appear. Rostral neuropore closes. Caudal neuropore remains open

'''9.5 days''': Dorsal curvature begins. Cardiac mass bulges under cephalic pole.

'''10.5 - 13.5 days''': Dorsal curvature increases. Body thickens. Softening of the cephalic domination straightens the embryo.

'''17.5 days''': Neck becomes visible.

==='''Limb Development'''===

''' 9.5 days''': Rostral limb bud appears

'''10.5 days''': Caudal limb bud appears

'''12.5 days''': Hand plate becomes present. Limbs become disposed.

'''13.5 days''': Foot plate and finger rays become visible.

'''14.5 days''': Rostral and caudal limbs become parallel.

'''15.5 days''': Elbow appears.

'''16.5 days''': Fingers start to elongate.

'''17.5 days''': Knee becomes visible

'''19.5 days''': Hands and feet merge on the midline. Three segments of limbs become distinguished.

==='''Abdominal Wall Development'''===

'''9.5 days''': Abdominal wall is limited to the embryonic pedicle under the cardiac mass.

'''13.5 days''': First intestinal loops appear in the umbilical cord.

'''14.5 days – 17.5''': Rapid intestinal development in the cord.

'''15.5 days''': Abdominal vesicles can be observed.

'''16.5 days''': Cecal bud becomes present outside the abdomen

'''18.5 days''': Bowel returns to the abdominal cavity and umbilical ring closes.

==='''Cephalic Development'''===

'''9.5 days''': One cerebral vesicle can be seen. Pharyngeal arches as optic vesicle are present.

'''10.5 days''': Three arches are distinguished in the cephalic pole.

'''11.5 days''': Three cerebral vesicles present. Optic plate is distinguished.

'''12.5 days''': Face develops nasal, maxillar and mandibular buds. Lens vesicle is closed. Five cerebral vesicles exist.

'''14.5 days''': The ear becomes refined. Face can be distinguished from the brow.

'''18.5 days''': Eyelid appears, covering the eyes.

==Staging==

The following stages have been adapted from Beaudoin et al. (2003). Table 1 represents at each age its corresponding stage defined by the Carnegie classification

{| class="wikitable" style="text-align:center; width: 800px; height:1000px" border="1"
|+'''Table 1. Rabbit developmental stages using Carnegie classification'''

|- style="height:50px"
! '''Stage''' !! '''Days''' !! '''Event''' !! '''Image'''
|- style="width:200px"
! width="50" | 10
| width="50" | 8.5 || First somites appear, rostral neuropore closes
|- style="height:75px"
! 12
| 9.5 || Rostral limb bud, embryonic pedicle, caudal neuropore closes, one cerebral vesicle, pharyngeal arches, completion of optic vesicle
| [[file: 9.5new.JPG|100px]]
|- style="height:75px"
! 13
| 10.5 || Dosral C-shaped curvature, caudal limb bud, prominent cardiac swelling, four pharyngeal arches
| [[file: 10.5new.JPG|100px]]
|- style="height:75px"
! 14
| 11.5 || Three cerebral vesicles, optic plate, mesonephric ridge
|- style="height:75px"
! 15
| 12.5 || Hand plate, wheel ray limbs, lens vesicle closes, five cerebral vesicles, facial buds, vertebrae
| [[file: 12.5new.JPG|100px]]
|- style="height:75px"
! 16
| 13.5 || Foot plate, finger rays, prominent liver, intestinal loops, auricular hillocks
| [[file: 13.5new.JPG|100px]]
|- style="height:100px"
! 19
| 14.5 || Cuboidal body, trunk straightens, parallel limbs, toe rays, modeled face, visible auricle
| [[file: 14.5new.JPG|100px]]
|- style="height:75px"
! 20
| 15.5 || Elbow, fingers elongate, notches between toe rays
| [[file: 15.5new.JPG|100px]]
|- style="height:75px"
! 21-22
| 16.5 || Toes free, cecal bud in intestinal hernia
| [[file: 16.5new.JPG|100px]]
|- style="height:75px"
! 22-23
| 17.5 || Knee, neck, eyelids
| [[file: 17.5new.JPG|100px]]
|- style="height:75px"
! 23
| 18.5 || Hands and feet join at the midline, closure of abdominal wall, eyelids cover eyes
| [[file: 18.5new.JPG|100px]]
|-
| colspan="4" align="center"| Following this stage fetal appearance is completed, organogenesis is achieved
|}

==Genetics==

===Sequencing===
The National Human Genome Research Institute selected the European rabbit (Oryctolagus cuniculus) for whole genome sequencing to enhance their understanding of the human genome and use it experimentally for an animal model for human disease. (8)

The rabbit has been sequenced twice by The Broad Institute as part of the mammalian genome project. It is now currently undergoing 7 more sequencing projects. Its sequencing is made by the Whole Genome Shotgun (WGS) and assembly method. (9) This is when genomic DNA is sheared into small pieces of approximately 2000 base pairs which are then cloned into plasmids and sequenced on both strands. Once the contig fragments are read, realigned and reassembled by computer algorithms, it will give the overall sequence. (10) (11) The image below shows diagramatically how the two types of sequencing are different. The same techniques are used for sequencing the human genome (in 2003). [A contig is a set of overlapping DNA segments, derived from a single source of genetic material, from which the complete sequence may be deduced.

The whole genome shotgun (WGS) has serious gaps, yet the information has already proven useful for immunological as well as in silico studies. Deeper 7x coverage started in September 2007. The NCBI Rabbit Genome Resources site has links to searches for genes in the assemblies of the 2x WGS sequence at Ensembl and UCSC.(12) [http://www.broadinstitute.org/models/europeanrabbit/ Rabbit Genome Project]

[[File:WGS_sequencing.gif‎|center|800 px]]

===Genome===
The Rabbit genome was published by two groups (9)
# Lindblad-Toh,K., Chang,J.L., Gnerre,S., Clamp,M. and Lander,E.S. published their admission of 84024 bases on May 5th 2005 to The Broad Institute (USA) by shotgun sequencing
# Di Palma,F., Heiman,D., Young,S., Gnerre,S., Johnson,J., Lander,E.S. and Lindblad-Toh,K. published their admission of 84024 bases on August 3rd 2009 to The Broad Institute (USA) by shotgun sequencing.
The rabbit's genome is sequenced and on display in the Nucleotide Data Bank. It is too long to produce here. A link to the data bank is provided: [http://www.ncbi.nlm.nih.gov/nuccore/256946799/ Rabbit Genome from the Nucleotide Data Bank]

[[File:8cellembryo.jpg|thumb|Individual mitochondria (arrowheads) of an 8cell Rabbit embryo]]

The rabbit genome was sequenced in 2005 by Ensembl and managed to produce: (13)
* 2,076,044,328 supercontigs (ordered Contigs with gaps)
* 495 Known protein-coding genes
* 11,357 Projected protein-coding genes
* 2,343 RNA genes
* 212,581 Gene exons
* 20,311 Gene transcripts

For further research the taxonomy ID number for the Rabbit is: 9986 [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=9986&lvl=3&lin=f&keep=1&srchmode=1&unlock/ Taxonomy Data]

===Mitochondrial Genome===
The mitochondiral genome (mtDNA) of the rabbit was sequenced on November 14th 2006 with 17245 base pairs/nucleotides in circular form. Apparently the "length is not absolute due to the presence of different numbers of repeated motifs in the control region".
PMID 9653643

The image to the right shows the mitochondria during cell division and multiplication in embryo development.

=== Chromosomes ===
Over the years there have been various data suggesting the diploid chromosomal number for the rabbit may range from 22-42. However through recent research and an abundance of trials suggest that the rabbit does indeed have 22 different chromosome pairs existing in each cell of the rabbit. (16)(17) The sex chromosomes of the rabbit are of X-Y type convincingly (17). In a study in Bombay it confirmed that a rabbit has 2n = 44 chromosomes. There were 21 pairs of autosomes, out of which 1 to 6 were metacentric, 7 to 11 submetacentric, 12 to 17 subtelocentric and 18 to 21 acrocentric, plus the sex chromosomes. The image to the left shows a female rabbit with no chromosomal abnormalities. (19)

'''Comparison to human chromosome:'''

Rabbit chromosomes 12, 19 and X were found to be completely homologous to human chromosomes 6, 17 and X, respectively. All other human chromosomes were homologous to two or sometimes three rabbit chromosomes. (14) Chromosome 12 was shorter than chromosomes 13 and 14. (15) The image below illustrates the human chromosome (2n = 46).

[[File:Drawn chromosome.jpg|left|400 px]]

[[File:Karyotypehuman.gif|right|500 px]]

'''Abnormalities'''

These are generally more apparent during early embryo development in blastocysts from delayed fertilization. Some examples of abnormal development include cases of: (18)
* hypoploidy; 1 chromosome missing from a pair (2n = 43),
* double hypoploidy; 2 chromosomes missing from 2 different pairs (2n = 42),
* mosaicism (different chromosomal makeup in some cells).

Another study also found these abnormalities as well as: (19)
* autosomal trisomy (3 autosomes per pair),
* triploidy (extra set of chromsomes),
* mixoploidy (unequal number of chromosome sets in adjacent cells), and
* short arm deletion (deletion of parts of chromosomes).

A specific abnormality occurring in rabbits is the x-linked tremor. There is a mutation in exon 2 of the prteolipid-protein (PLP 1) gene, corresponding to the end of the first potential transmembrane domain of the protein. This disorder affects myelination of the central nervous system. OMIA ID:12 [http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=full_report&list_uids=100009169&log$=omiamaingene| Gene:100009169]

==Abnormal Development==

Abnormal embryological development is a vast field of study that has been the subject of recent research papers. Our investigation of abnormal development in rabbit embryology will focus on abnormalities commonly found in both rabbit and human embryos. We will explore the nature of these abnormalities in both humans and rabbits.

[[File:Normal v Abnormal.jpg|right|300 px|thumb|Brain MRI of patient with Hydrocephalus (left) compared to a normal brain (right). An obvious increase in ventricular size and a significant decrease in brain size is present.]]
[[File:Ventricle_Expansion.jpg|right|300 px|thumb|CSF accumulation in ventricles of brain increasing intracranial pressure.The pressure from the expanding ventricles force the brain and skull to grow outwards abnormally.]]

'''Hydrocephalus'''

Annually, one in every 1000 children born in Australia have hydrocephalus. Hydrocephalus occurs when excessive cerebrospinal fluid (CSF) accumulates in the brain and can result in severe disability and even death because the disorder can result in complete or near complete destruction of the cerebral cortex (22).

Children born with hydrocephalus typically exhibit abnormally large head circumference and bulging cranial fontanels as a result of increased intracranial pressure on the brain from the accumulating CSF (22,23). As CSF accumulates in the ventricles and CSF compartments of the brain, it expands forcing the brain to grow outward. The outward growing brain places pressure on the skull which in turn also grows outwards giving rise to an abnormally large head circumference and bulging cranial fontanels (22,24). It is generally acknowledged that children with hydrocephalus have mental retardation, often to the degree of being “vegetative” (24).

The serious consequences of this disease mean that much research is necessary to unearth methods of prevention and effective treatment. One of the modes of studying hydrocephalus is to use the rabbit experimental model where hydrocephalus can be induced in rabbit embryo’s. The injection of silicone oil into the cisterna magna of the brain is one way of inducing hydrocephalus in the rabbit embryo. The silicone oil obstructs the normal flow of CSF resulting in CSF accumulation in the brain leading to hydrocephalus (25). Another method of inducing hydrocephalus in rabbit embryo’s is by intentional vitamin A deprivation of pregnant dams. The vitamin A deficiency results in raised intracranial CSF pressure and aqueduct stenosis causing poor circulation of CSF leading to hydrocephalus (26,27). Although the exact function of vitamin A on brain development and CSF regulation is not fully understood, it is clear that Vitamin A has an important role in brain development and its normal functioning (27).
[[File:Rabbithhdrocephalus.jpg|center|300 px|thumb|Young rabbit with hydrocephalus caused by Vitamin A deficiency. Note the abnormally shaped cranium inflamed in appearance.]]

[[File:SpinabifidaMeningocele1.jpg|right|300 px|thumb|Spina Bifida Meningocele has characteristic damage to the meninges of the spinal cord which are pushed out through an opening in the vertebrae as a cyst filled with CSF.]]
[[File:SpinaBifidaMyelomeningocele.jpg|right|300 px|thumb|Spina Bifida Myelomeningocele is the most severe form of spinabifida where the damaged spinal cord protrudes out with damaged meninges as a cyst filled with CSF.]]
[[File:SpinaBifidaOcculta1.jpg|right|300 px|thumb|Spina Bifida Occulta is the least severe as the spinal cord and meninges are undamaged.]]

'''Spina Bifida'''

In Australia, the risk of spina bifida is 1 in every 500 pregnancies. Spina bifida is a type of neural tube defect where vertebrae (which normally cover and protect the spinal cord) are not completely formed but are divided resulting in the defective spinal cord and its coverings to protrude through the opening (28,29).

There are three main types of Spina Bifida differentiated by their characteristic features:

1)Spina Bifida Meningocele characterized by normal spinal cord, divided outer vertebrae and meninges surrounding the spinal cord protruding from the divided vertebrae as a cyst (1,28).

2)Spina Bifida Myelomeningocele characterized by split outer vertebrae with spinal cord and its meninges protruding from the divided vertebrae as a cyst. Commonly found at lumbar vertebral level (1,28,29).

3)Spina Bifida Occulta characterized unfused vertebral arches and exposed vertebral canal. Spinal cord and its meninges still located in vertebral canal (1,28).

All forms of spina bifida are potentially fatal and in those where the spinal cord is damaged severe consequence arise including and paralysis and loss of sensation at and below the level of damage spinal cord damage (29,33). There is a lot of Spina bifida research using rabbit models to test the effective methods of correcting spina bifida. The occurrence of natural spina bifida in rabbits is rare and for experimental purposes it can be surgically created in rabbit fetuses during gestation (31,32). The process involves aesthetical sedation of the maternal rabbit at day 22 of gestation; a midline laparotomy performed and the desired type of spina bifida lesion created on the exposed fetus using forceps. Different methods for correcting spina bifida can then be tested and its effectiveness analysed (30,33,34).
[[File:Rabbitspinabifida1.jpg|center|350 px|thumb|Rabbit newborn with Spina Bifida. Note the unfused, divided vertebrae and exposed spinal cord.]]

'''Brachydactylia & Acheiropodia'''

[[File:Malformation1.jpg|right|150 px|thumb|Acheiropodia in rabbit characterized by amputations of the limbs and extremities.]]

[[File:Rabbitmalformation3.jpg|left|150 px|thumb|X-Ray study of rabbit limbs with malformed phalanges due to Brachydactylia.]]

Brachydactylia and Acheiropodia are genetic disorders characterized by skeletal malformation of the hands and feet (36,36). In Brachydactylia, the malformations commonly involve abnormal shortening of fingers and toes due to poorly formed or absent bones (35). Acheiropodia is characterized by more severe skeletal malformations including bilateral amputations of the distal upper and lower extremities as well as aplasia of the hands and feet. Although it is not fatal, the individual endures a very difficult life without hands and feet (37).

The inheritance mechanism of this diseases can has been studied through experiment using rabbits. Rabbits with abnormal genes coding for Brachydactylia and Acheiropodia are selected and bred to produce offspring with the disease (36). Brachydactylia and Acheiropodia are autosomal recessive disorders which means that two copies of an abnormal gene must be present in the affected individual in order for the disease to develop. Thus, each parent passes an abnormal gene to the offspring (35,36). The process of the malformation progresses from genotype to phenotype; small deletions on the chromosomes produce abnormal genes, the abnormal genes are then passed down to the offspring, the offspring that inherits two of the abnormal genes is unable to code for the correct proteins and as a result, there is failure in normal development of limb extremities in the embryo phenotype (37,38).

==Current Embryology Research==

There is currently great excitement in research involving rabbits in the fields of transgenesis, cloning and stem cells. We shall explore research in these areas by discovering some of the techniques used and how they have been applied to the rabbit model.

[[File:Trans1.jpg|right|170 px]]
[[File:Trans2.jpg|right|170 px]]
[[File:Trans3.jpg|right|170 px]]
[[File:Trans4.jpg|right|170 px]]
[[File:Trans5.jpg|right|170 px]]

'''Transgenic rabbit'''

A transgenic organism is one whose genome also contains genes from another species (39). The aim of creating a transgenic organism is to obtain a favorable characteristic in the organism’s phenotype (41). This desired characteristic of phenotype is obtained by altering the organism’s normal genotype to include the gene from another species with the desired characteristic (39,40).

The production of a transgenic organism involves several steps summarized below:

1) The chromosome and the desired gene on it are identified in an organism (39).

2) The gene is isolated from its DNA strand. This involves “cutting” it out of its DNA strand using enzymes called restriction endonucleases. The restriction endonucleases cut DNA at specific site so the desired gene can be removed from the DNA strand. The cut ends are known as “sticky ends” (39,40).

3) Separate DNA sequences for regulation sometimes have to be added to ensure the gene will work (40).

4) The gene is then inserted with a promoter sequence into the fertilized egg cell of a new organism producing recombinant DNA (39,44). To do this, firstly the new organism’s cell DNA must first be cut and the desired gene incorporated into it. The same enzymes are used to cut the new organism’s cell DNA because the DNA stands from the two different organisms will form matching sticky ends that will be attracted to and connect with each other in a process is called “annealing” (39,40,44).

5) DNA ligases are sealing enzymes found in all living organisms that help make and repair DNA (39,40). The DNA ligases are added to the annealed DNA fragments to help strengthen the bonds of the new recombinant DNA. The recombinant DNA is now transferred into the new organism’s fertilized egg by microinjection (44).

6) As the embryo develops and the recombinant genetic code read, new proteins are synthesized which code for the new desired phenotype characteristic in the transgenic organism (39,40).

Transgenic rabbits can be created in the laboratory by gene microinjection into the fertilized rabbit oocyte (44). In April 2000, a transgenic rabbit named Alba was born containing a gene from a Pacific Northwest jellyfish. The gene which was injected into a fertilized albino rabbit oocyte allows the rabbit to synthesize the green fluorescent protein (GFP) that is characteristic of the Pacific Northwest jellyfish. When illuminated correctly, Alba glows a bright green (43,46).

Transgenic rabbits have important research purposes. Transgenic rabbits can be created to model retinal degeneration (44). Retinal degeneration is a common problem with aging and diseases such as diabetes, and frequently leads to complete blindness (42). A genetic retinal degeneration disease called retinitis pigmentosa (RP) is created in these rabbits by introducing the “Pro347Leu” mutation of the rhodopsin gene into fertilized rabbit eggs (43,44). As the rabbit grows, it develops the disease which becomes progressively worse (45).
The use of these transgenic rabbits ultimately leads to better understanding of the disease and more effective treatments (42). [[File:Transgenic rabbit.jpg|center|250 px|thumb|"Alba" A trangenic rabbit with a gene from a Pacific Northwest jellyfish that allows it to synthesize the green fluorescent protein (GFP) of the jellyfish.]]

[[File:Crabbit 1.jpg|right|170 px]]
[[File:Rabbit2.jpg|right|170 px]]
[[File:Rabbit3.jpg|right|170 px]]
[[File:Crabbit 4.jpg|right|170 px]]

'''Cloning'''

Cloning is a method of producing genetically identical organisms. The principle of cloning relies on “tricking” an egg cell to begin rapidly dividing into an embryo (39). In the normal fertilization process, two haploid sex cells unite to form a diploid zygote which begins rapidly dividing into an embryo (40). By replacing the haploid egg cell nucleus with a diploid somatic cell nucleus, the egg cell is tricked into thinking it is fertilized and hence begins rapidly dividing to form an embryo (39,40,41).

The process of cloning involves several steps summarized as the following using a rabbit example:

1) A somatic cell is obtained from a rabbit and the nucleus removed (39).

2) An egg cell is obtained from a donor rabbit and the nucleus of the egg cell removed using an enucleation needle. The cell is now called an enucleated egg cell (egg cell without a nucleus) (39,41).

3) The nucleus of the somatic cell is inserted into the enucleated egg cell (41).

4) The cell is now stimulated to divide by applying pulses of electric current (39).

5) The rapidly dividing cell develops in culture for a few days forming the early embryo (40,41).

6) The embryo is then implanted into the uterus of another rabbit similar to the egg cell donor. This rabbit is called the surrogate mother (40,41).

7) The embryo develops and the surrogate mother gives birth to a rabbit fetus with near identical genotype of the somatic cell donor (the small genomic difference is caused by the fetus obtaining mitochondrial DNA from the egg cell donor) (39,41).

The cloning of rabbits has been achieved by inserting the diploid nucleus of a rabbit fibroblast (the principal cells in connective tissue) into an enucleated oocyte (49). There is currently much focus on the creation of controversial but revolutionary interspecies hybrid embryos where the nucleus from a human somatic cells are implanted into an enucleated egg cell of another animal (50). The resulting embryo (known as a chimera) will be almost completely human genotype but will have genome from the other animal (48). In 2003, scientists at the Shanghai Second Medical University fused human cell with rabbit eggs creating the first human-rabbit hybrid using the nucleus transfer technique. The hybrid embryo developed in culture for a few days before it was destroyed and the stem cells harvested (47,48). The purpose of the research into creating hybrid embryos is to provide researchers with human stem cells for experimentation into cures for diseases such as cystic fibrosis, Alzheimer’s and Motor Neuron disease as human stem cell are difficult to obtain (50).

[[File:Rabbit clone.jpg|center|450 px|thumb|(A) Cloned rabbits (5 month old) from nuclear transfer technique. (B) The male rabbit whose fibroblasts were used as the nuclear donors. The cloned rabbits have almost identical genome to the male donor.]]

'''Stem Cells'''
[[File:HES.jpg|right|200 px|thumb|Human Embryonic Stem cell (hES).]]
[[File:Rabbit knee.jpg|right|200 px|thumb|Stem cell induced cartilage repair of knee in rabbit.]]

Stem cells are unspecialized cells which are able to continuously reproduce themselves and under appropriate conditions, differentiate into all the various specialized cells of the organism such as cardiac cells, neurons and blood cells (39,40). Adults have a small number of stem cells when compared to a developing embryo and the stem cell of an embryo more easily obtained (41). Human embryonic stem cells (hES) derived from the inner mass of the preimplantation blastocyst have the potential to differentiate into all cell types in the human body and thus are valued by researchers (50). However, due to ethical and political issues, the obtaining and experimentation on human embryonic stem cells is difficult and alternate means are needed as stem cell provides potentially new treatments for a range of diseases (54).

Rabbits can be used both in the obtaining of stem cell for experimentation and also as recipients of stem cells to cure diseases. The human-rabbit hybrid embryo provides a method of obtaining stem cells for experimentation and these stem cells possess many similar properties to human stem cells, including expression of surface markers, special growth requirements, capabilities of self renewal, formation of embryonic body and differentiation into cells of all three germ layers (53).

Stem cell experimentation on rabbits also focuses on transplanting stem cell into rabbits to treat specific diseases. A study at Zhejiang University where a research team transplanted human mesenchymal stem cell into New Zealand white rabbits with myocardial infarction recoded regeneration of vascular structure and improvement in cardiac function. The research team noted the potential of stem cells in differentiating into specialized cardiac cells when subjected to the specific conditions of the rabbit heart (52).

Another study at Hallym University tested the effectiveness of transplanting mesenchymal stem cells from New Zealand white rabbits into damaged cartilage in the knees of other New Zealand white rabbits. In the experiment, mesenchymal stem cells were obtained from the rabbit bone marrow and injected into the knees of other rabbits that had cartilage in their knees surgically damaged. The research team were able to conclude notable cartilage recovery in the rabbits with the mesenchymal stem cell injection and the potential of mesenchymal stem cells to differentiate into fibroblasts, adipoblasts, osteoblasts and chondroblasts (51,53).

The findings in stem cell experimentation with in rabbits yielded positive results and potentially opens a new field of research in the use of stem cell to treat a range of diseases in humans.

==References==

# Dr Mark Hill 2009, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G [6]
# E.Horne Craigie, University of Toronto Press 1948, Bensley's Practical Anatomy of the Rabbit 8th Edition
# Ankum WM, Houtzager HL, Bleker OP (1996). "Reinier De Graaf (1641-1673) and the fallopian tube". Human Reproduction Update 2 (4): 365–9. doi:10.1093/humupd/2.4.365. PMID 9080233.
# Jocelyn HD, Setchell BP (December 1972). "Regnier de Graaf on the human reproductive organs. An annotated translation of Tractatus de Virorum Organis Generationi Inservientibus (1668) and De Mulierub Organis Generationi Inservientibus Tractatus Novus (1962)". Journal of Reproduction and Fertility. Supplement 17: 1–222.
# Jay, V. (2000). "A portrait in history. The legacy of Reinier de Graaf". Archives of Pathology & Laboratory Medicine 124(8): 1115–6.
# Lois N Magner. "A history of the Life Sciences" 3rd edition
# J. D. Biggers. (1991). Walter Heape, FRS: a pioneer in reproductive biology.Centenary of his embryo transfer experiments Laboratory of Human Reproduction and Reproductive Biology, and Department of Cellular and Molecular Physiology, Harvard Medical School, Boston, MA 02115, USA
# National Center for Biotechnology Information. (June 16, 2009). ''Rabbit Genome Resources'', Retrieved August 20, 2009, from [http://www.ncbi.nlm.nih.gov/projects/genome/guide/rabbit/ NCBI Rabbit Genome Site]
# The Broad Institute. (2008). ''Rabbit Genome Sequencing Project''. Retrieved only August 29, 2009, from [http://www.broadinstitute.org/models/europeanrabbit/ Rabbit Genome Sequencing Project]
# Campbell, M. A. (2002). ''Sequencing Whole Genomes: Hierarchical Shotgun Sequencing v. Shotgun Sequencing'' Retrieved August 31, 2009, from [http://www.bio.davidson.edu/courses/GENOMICS/method/shotgun.html/ Shotgun Sequencing - 1]
# Trivedi, B. (2000). ''Sequencing the Genome''. Retrieved September 4, 2009, from [http://www.genomenewsnetwork.org/articles/06_00/sequence_primer.shtml Shotgun Sequencing - 2]
# Mage, R. (2008). Rabbit genome sequencing update: genes of immunological interest found in the 2x genome assemblies, ENCODE, and the 7x trace archive. ''Journal of FASEB'' 22(Retrieved September 5, 2009, from [http://www.fasebj.org/cgi/content/meeting_abstract/22/2_MeetingAbstracts/559/ Rabbit Genome & its Immunological Interest]
# Ensembl (2009). ''Rabbit (Oryctolagus cuniculus)''. Retrieved September 5, 2009, from [http://www.ensembl.org/Oryctolagus_cuniculus/Info/Index/ Ensembl Genome Project]
# Korstanje, R. et al. (1999) Complete homology maps of the rabbit (Oryctolagus cuniculus) and human by reciprocal chromosome painting. ''Cytogenetics and cell genetics'' ''86''(3-4), 317-322. Retrieved September 6, 2009, from [http://cat.inist.fr/?aModele=afficheN&cpsidt=1189693/ Complete homology maps of the rabbit Article] "PMID 10575232"
# Brunner, R., Knopp, A., Rudolph, W. (n.d). Rabbit chromosome analysis by image processing. ''Journal of Applied Rabbit Research''.
# DebMark Rabbit Education Resource (2006). ''Rabbit Genetics''. Retrieved September 6, 2009, from [http://www.debmark.com/rabbits/genetics.htm/ Rabbit Genetics]
# Painter, T. (2009) Studies in mammalian spermatogenesis VI. The chromosomes of the rabbit. ''Journal of Morphology''. ''43''(1): 1-43.
# Hofsaess, F., and Meacham, T. ( 1995) Chromosome abnormalities of early rabbit embryos. ''Journal of Experimental Zoology''. ''177'' (1): 9-11 [http://www3.interscience.wiley.com/journal/110490865/abstract/ Chromosome abnormalities]
# Martin-Deleon, P., Shaver, E., and Gammal, E. (1973) Chromosome abnormalities in rabbit blastocysts resulting from spermatozoa aged in the male tract. ''Fertility and Sterility''. ''24''(3):212-219.
# Patil, M. et al (2004) Chromosome analysis of domestic rabbit. ''The Journal of Bombay Veterinary College''. ''12'' (1 and 2)
#Biggers J.D (1991) Walter Heape FRS: a pioneer in reproductive biology. centenary of his embryo transfer experments.''Journals of reproduction and fertility''. ''93''(1)
# Stoodley, M (2006). Hydrocephalus. Prince of Wales Clinical School. Retrieved from [http://www.brainaustralia.org.au/AZ_of_Brain_Disorders/hydrocephalus]
# National Institute of Neurological Disorders and Stroke (2008, February). Hydrocephalus Fact Sheet. Retrieved from [http://www.ninds.nih.gov/disorders/hydrocephalus/detail_hydrocephalus.htm]
# Lewin, R (1999). Is Your Brain Really Necessary?. 24) Developmental Medicine & Child Neurology, 41. Retrieved from [http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=176431]
# Bigio, M.R, & Bruni J.E (1991). Silicone oil-induced hydrocephalus in the rabbit . Child's Nervous System, 7(2), Retrieved from [http://www.springerlink.com/content/b011477724837152/]
# Geelen, J.A (1974). A case of hydrocephalus and meningoencephalocele in a rabbit, caused by aqueductal malformation. Laboratory Animals, 8(2), Retrieved from [http://la.rsmjournals.com/cgi/content/abstract/8/2/167]
# LAMMINGX, G.E (1954). 27) Hydrocephalus in Young Rabbits Associated with Maternal Vitamin A Deficiency. British Journal of Nutrition, 8(2), Retrieved from [http://journals.cambridge.org/download.php?file=%2FBJN%2FBJN8_04%2FS0007114554000554a.pdf&code=10bb1dbc4a9e57a091f4e05f6aebbcf2]
# Carney, A (2008, February ). Spina bifida. Retrieved from [http://www.spinabifida.asn.au/]
# Better Health Channel (2008, October ). Spina bifida explained . Retrieved from [http://www.betterhealth.vic.gov.au/bhcv2/bhcarticles.nsf/pages/Spina_bifida_explained]
# Peeters, M.C, Viebahn, C, & Hekking, J.W (1998). Neurulation in the rabbit embryo . Anatomy and Embryology, 197(3), Retrieved from [http://www.springerlink.com/content/1efyteewgetjlwyg/]
# George, T.M, & Fuh E (2003). Review of Animal Models of Surgically Induced Spinal Neural Tube Defects: Implications for fetal surgery. Pediatric Neurosurgery , 39(2), Retrieved from [http://content.karger.com/produktedb/produkte.asp?typ=fulltext&file=PNE2003039002081]
# Pedreira, D.A, & Valente P.R (2002). A Different Technique to Create a 'Myelomeningocele-Like' Defect in the Fetal Rabbit. Fetal diagnosis and therapy, 17(6), Retrieved from [http://content.karger.com/ProdukteDB/produkte.asp?Doi=65388]
# Patten, B.M (1953). Embryological stages in the establishing of myeloschisis with spina bifida. The American journal of anatomy, 93(3), Retrieved from [http://deepblue.lib.umich.edu/handle/2027.42/49611]
# Pedreira, D.A, & Valente P.R (2003). Successful Fetal Surgery for the Repair of a 'Myelomeningocele-Like' Defect Created in the Fetal Rabbit. Fetal Diagnosis and Therapy, 18. Retrieved from [http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowPDF&ProduktNr=224239&Ausgabe=229041&ArtikelNr=69378]
# Lecklitner, M.L, & Douglas K.P (1986). Osteoscintigraphy and brachydactylia of the hand . European Journal of Nuclear Medicine and Molecular Imaging, 12(9), Retrieved from [http://www.springerlink.com/content/t82l77282x579102/]
# Greene, H.S, & Saxton J.A (1938). HEREDITARY BRACHYDACTYLIA AND ALLIED. ABNORMALITIES IN THE RABBIT. THE JOURNAL OF EXPERIMENTAL MEDICINE , 69. Retrieved from [http://jem.rupress.org/cgi/reprint/69/2/301.pdf]
# P. Ianakiev, M. van Baren, M. Daly, S. Toledo, M. Cavalcanti, J. Neto, E. Silveira, A. Freire-Maia, P. Heutink, M. Kilpatrick. Acheiropodia Is Caused by a Genomic Deletion in C7orf2, the Human Orthologue of the Lmbr1 Gene. The American Journal of Human Genetics, 68. Retrieved from [http://linkinghub.elsevier.com/retrieve/pii/S0002929707624707]
# Walbaum, R, Hazard, C, & Cordier, R (1976). Brachydactylia with symphalangism, probably autosomal recessive . Human Genetics, 33(2), Retrieved from [http://www.springerlink.com/content/m630p6880661486n]
# Campbell, N.A, & Reece, J.B (2002). Biology 6th Edition. USA: Benjamin Cummings.
# Solomon, E.P, Berg, L.R, & Martin, D.W (2002). Biology 6th Edition. USA: Thompson Learning.
# Glanville, A.R (2008). Scientifica. NSW, Australia: Millennium House.
# Lund, R.D (2008). Saving Vision with Skin Cells. Retrieved from [http://www.blindness.org]
# Jones, B.W, & Marc R.E (2008). Computational Molecular Phenotyping and Excitation Mapping in the P347L. Retinal Degeneration , (2986), Retrieved from [http://prometheus.med.utah.edu/]
# Kondo, M, Sakai, T, & Ueno, S (2009). Generation of a Transgenic Rabbit Model of Retinal Degeneration. Investigative Ophthalmology and Visual Science, 50. Retrieved from [http://www.iovs.org/cgi]
# Punzo, C, Chen, B, & Roesch, K (2009). PHOTORECEPTOR DEATH IN MOUSE MODELS OF RETINITIS PIGMENTOSA. Retrieved from [http://genepath.med.harvard.edu]
# Zimmer, M (2008). Alba. Retrieved from [http://www.conncoll.edu/ccacad/zimmer/GFP-ww/cooluses8.html]
# Scott, C (2006, May 1). Chimeras in the crosshairs. Nature Biotechnology , 24, Retrieved from [http://www.nature.com/nbt/journal/v24/n5/abs/nbt0506-487.html]
# Mott, M (2005, January 25). Animal-Human Hybrids Spark Controversy. National Geographic News, Retrieved from [http://theyfly.com/PDF/Nat.%20Geo.%20Animal-Human%20Hybrids.pdf]
# Li, S, & Chen X (2006). Rabbits generated from fibroblasts through nuclear transfer . Society for Reproduction and Fertility, 131. Retrieved from [http://www.reproduction-online.org/cgi/reprint/131/6/1085]
# Minger, S (2007). Interspecies SCNT derived human embryos. Regenerative Medicine, 2(2), Retrieved from [http://www.futuremedicine.com]
# Koga, H, Shimaya, M, & Muneta, T (2008). Local adherent technique for transplanting mesenchymal stem cells as a potential treatment of cartilage defect. Arthritis Research & Therapy, 10(4), Retrieved from [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2575632]
# Wang, J, Li, C, & Sun, Y (2005). Human bone marrow-derived mesenchymal stem cells transplanted into damaged rabbit heart to improve heart function. Journal of Zhejiang University Science, 6(4), Retrieved from [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1389731]
# Chen, Y, Liu, A, & Mao, W (2003). Embryonic stem cells generated by nuclear transfer of human somatic nuclei into rabbit oocytes. Cell Research , 13(4), Retrieved from [http://www.nature.com]
# Bethesda (2009, September 23). Stem Cell Information. Retrieved from [http://stemcells.nih.gov]
# Cibelli, J. B. (2002). Principles of cloning Amsterdam. Academic Press
# European rabbit (oryctolagus cuniculus) Retrieved 9/21/2009, 2009, from http://www.feral.org.au/content/species/rabbit.cfm
# Warner, S. (2003). Inositol transport in preimplantation rabbit embryos: Effects of embryo stage, sodium, osmolality and metabolic inhibitors Reproduction, 125(4), 479-493.
# Derelanko, M. J. (2008). The toxicologist's pocket handbook, second edition Informa HealthCare
# Beaudoin, S., Barbet, P., & Bargy, F. (2003). Developmental stages in the rabbit embryo: Guidelines to choose an appropriate experimental model Fetal Diagnosis and Therapy, 18(6), 422-427.

==Glossary==

Anesthetic - A drug that causes temporary loss of bodily sensations

Aplasia - The absence or defective development of a tissue or organ

Blastocyst - A stage of embryo development that occurs about five days after fertilisation when the embryo contains quite a few cells

Caudal - Situated towards the inferior or posterior end of the body

Cephalic - Relating to the head

Cerebral Aqueduct - A canal filled with cerebrospinal fluid within the midbrain

Cerebral Cortex - The layer of unmyelinated neurons (the grey matter) forming the cortex of the cerebrum of the brain

Cerebro Spinal Fluid (CSF) - A watery fluid which flows in the cavities within the brain and around the surface of the brain and spinal cord

Chromosome - Microscopic carriers of genetic material, composed of deoxyribonucleic acid (DNA) and proteins and appearing as rods under a microscope

Cisterna Magna - is one of three principal openings in the subarachnoid space between the arachnoid and pia mater layers of the meninges surrounding the brain

Diploid - A full set of genetic material, consisting of paired chromosomes one chromosome from each parental set

Dorsal - Position towards the back

Fontanel - Membranous gap between the bones of the cranium in an infant or fetus

Genome - All genetic information, the entire genetic complement and all of the hereditary material possessed by an organism. Made up of both chromosomal genome (inside the nucleus of the cell in the familiar form of chromosomes) and mitochondrial genome (outside the nucleus in the cytoplasm of the cell, usually in the form of one round chromosome (the mitochondrial chromosome))

Genotype - The genetic makeup of an organism

Glucocorticoids - A class of steroid hormones that bind to the glucocorticoid receptor (GR), which is present in almost every vertebrate

Haploid - A single set of chromosomes (half the full set of genetic material)

Laparotomy- Surgical incision into the abdominal wall; often done to examine abdominal organs

Ligases - Group of enzymes that catalyze the binding of two molecules

Oocyte - A female gametocyte that develops into an ovum after two meiotic divisions

Phenotype - The observable traits or characteristics of an organism, for example hair color, weight, or the presence or absence of a disease.

Pronuclear - Haploid nucleus before fusion of nuclei in fertilisation

Restriction Endonucleases - Enzymes that recognize and cleave specific DNA sequences, generating either blunt or single-stranded (sticky) ends

Retina - The thin layer of cells at the back of the eyeball where light is converted into neural signals sent to the brain

Rostral - Situated toward the oral and nasal region

Somite - Blocks of mesoderm on either side of the notochord and neural tube during development of the vertebrate embryo. Develop into muscles and vertebrae

Stenosis - Abnormal narrowing of a bodily canal or passageway

Weaning - Young become accustom to nourishment other than suckling

==Links to Research Laboratories and Researchers==

1) Transgenic lab: [http://www.dnavision.be/index.php]

Involved in development of transgenic organisms, DNA construction and phenotype analysis.

2) World Rabbit Science Association: (WRSA) [http://world-rabbit-science.com]

International Association where researchers exchange knowledge and encourage teaching, scientific research, practical experimentation, the collection and publication of statistics and documents relating to the rabbit. Even have their own journal called “World Rabbit Science”

Website provides contact with researchers, professors and veterinarians working with rabbits.

Example: Dr. Myriam Kaplan-Pasternak, Doctorate Veterinary Medicine, University of California, myriamsemail@gmail.com

3) American Veterinary Medical Association [http://www.avma.org]

The American Veterinary Medical Association (AVMA), established in 1863, is a not-for-profit association representing more than 78,000 veterinarians working in private and corporate practice, government, industry, academia, and uniformed services. Excellent website into animal research and has a range of veterinary journals.

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2009 Group Project 1

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Z3185685: /* Introduction */

[[File:Rabbits.png|right|400 px]]

== '''THE RABBIT (ORYCTOLAGUS CUNICULUS)''' ==

==Introduction==

[[File:Isidro_Martinez.jpg‎|left|175 px]]

Several characteristics of the rabbit make it an excellent model for study. This will be further explored in "The History of Model Use" section of this page. Many studies have resulted in the development and improvement of various micro-manipulation techniques such as the production of transgenic rabbits. The rabbit is an appropriate animal model as the results from many experiments are significant to that of other mammals, including humans. (55)

A rabbits potential for reproduction is high, breeding from the early stages of 3 to 4 months of age. A mature female rabbit can be pregnant from 6 to 8 months in a year, producing up to 30 to 40 young in this time. (56)

==History of Model Use==

'''WHY are we using rabbits?'''

ADVANTAGES
*Provides repeatability of animal model studies
*Large enough for single samples
*Many stocks/strains as animal models
*Easily managed
*Quality of immunologic products
*Ease of reproductive control

DISADVANTAGES
*Most colonies are a storehouse of diseases
*Extremely variable to responses to general anesthetics

'''Brief timeline of rabbit embryo model use'''

*1672- de Graaf found the Graffian follicle.
*1890- Walter Heape succeeded first mammalian embryo transfer
*1906- FT Lewis discovered the development of the lymphatic system in rabbit embryos.
*1941- Dr. Pincus succeeded in keeping rabbit embryos developing in the test
*1968- Edwards and Gardner successfully performed the first known embryo biopsy on rabbit embryos

=== Regnier de Graaf (1641–1673) ===
[[image:Ovary_Graaf.jpg|thumb|250px|left|drawing of ovary]]
[[File:Regnier de Graaf.jpg|right]]

'''Discovery of the Graafian Follicles'''

In 1672 de Graaf published ''The Generative Organs of Women'', which was primarily a study of development in the rabbit. When de Graaf discovered large, round welling on the ovaries of rabbits, he assumed they were mammalian eggs. De Graaf also described the corpus luteum.

He summarised the previous works from anatomists, but unable to experience the amazing benefits made by microscopy.
But Antonie van Leeuwenhoek (A microbiologist, 1632 - 1723) argued that the structures now known as Graafian follicles could not be eggs. Haller suggested that the egg might be formed by the coagulation of the fluid within the Graafian follicle. De Graaf noted that the “egg” did not contain a tiny embryo, but he thought it did contain the “germ” of the future organism. (3)

=== Walter Heape (1855-1928) ===
'''First case of embryo transfer experiments'''

On 27 April 1890, Walter Heape (a professor and physician at the University of Cambridge, England) transferred rabbit embryos from one mother to another. (7) One rabbit mother became pregnant and delivered young from the transferred embryos. This was the first mammalian embryo transfer experiment to be successfully completed. His embryo transfer work in perspective as it relates to other contributions of this pioneer in reproductive biology.(7)

In 1891, Walter Heape had been conducting research on reproduction in numerous animal species. Working with two species of rabbits, he flushed embryos from the rabbit fallopian tubes of one breed (Angora) and placed them into the uterus of a recently mated Belgian hare. In the resulting litter, there were 4 Belgians and 2 Angoras. Heape proved that it was possible to take preimplantation embryos and transfer them to a gestational carrier without affecting their development.(7)

===Dr. Gregory Goodwin Pincus (1903-1967) ===

'''Contraceptive pill'''

Dr. Pincus began studying hormonal biology and steroidal hormones early in his career. His first breakthrough came when he was able to produce in vitro fertilization in rabbits (by using chemicals) in 1934. Throughout their hormonal contraceptive research Pincus, along with reproductive physiologist Min Chueh Chang, found out progesterone would act as an inhibitor to ovulation. They co-invented the combined oral contraceptive pill.[2][6]

===Genetic Diagnosis===
In 1968, Robert Edwards and David Gardner reported the successful sexing of rabbit blastocysts, setting the first steps towards PGD (Preimplantation Genetic Diagnosis). It was not until the 1980s that human IVF was fully developed, which coincided with the breakthrough of the highly sensitive polymerase chain reaction (PCR) technology. Handyside and collaborators' first successful attempts at testing were in October 1989 with the first births in 1990 though the preliminary experiments had been published some years earlier. In these first cases, PCR was used for sex determination for patients carrying X-linked diseases.(12)

==Timeline of Embryo Development==

The following is a timeline, adapted from Cibelli (2002), of the main events of preimplantation development in rabbits. The time is measured in hours post-mating and shows the embryo stage (cell number) in each time scale.

[[File:Morula1.JPG|right|200 px|thumb|A day 2 early morula]]

'''12-14 hours:''' Oocyte; Fertilization

'''18-20 hours:''' Zygote; Pronuclear formation

'''24-26 hours:''' Two cell

'''30-32 hours:''' Four cell

'''38-40 hours:''' Eight cell; Maternal-zygotic transition

'''46-48 hours:''' Sixteen cell

'''54-56 hours:''' Morula (32 cell); Compaction and transport to uterus

'''64-66 hours:''' Compact morula (64 cell); Morula-blastocyst transition

'''76-78 hours:''' Early blastocyst (128 cell)

'''84-86 hours:''' Expanded blastocyst (256 cell); Blastocoels expansion

'''94-96 hours:''' Hatched blastocyst (512 cell); Hatching

The following shows a diagrammatic representation of the relative sizes of rabbit embryos. The sizes do not include the embryonic coverings such as the zona pellucida and mucin coat. This diagram has been adapted from Warner (2003).

[[File:Sizes.JPG]]

The following timelines show a comparison of the developmental stages between human and rabbit embryos. They have been adapted from Derelanko (2008). "The similarities of this developmental pattern in humans and rabbits, suggests that the same growth increment is required to achieve the same stage. The main difference observed between human rabbit gestational duration is due to the fetal growth phase. The reason for this may be due to birth weight, lifetime and the neural complexity of the species." (59)

[[File:Timeline_rabbit.JPG]]

The following timelines have been adapted from a study carried out by Beaudoin et al. on the development of rabbit embryos.

==='''Body Form'''===

'''8.5 days''': Embryo thickens. First somites appear. Rostral neuropore closes. Caudal neuropore remains open

'''9.5 days''': Dorsal curvature begins. Cardiac mass bulges under cephalic pole.

'''10.5 - 13.5 days''': Dorsal curvature increases. Body thickens. Softening of the cephalic domination straightens the embryo.

'''17.5 days''': Neck becomes visible.

==='''Limb Development'''===

''' 9.5 days''': Rostral limb bud appears

'''10.5 days''': Caudal limb bud appears

'''12.5 days''': Hand plate becomes present. Limbs become disposed.

'''13.5 days''': Foot plate and finger rays become visible.

'''14.5 days''': Rostral and caudal limbs become parallel.

'''15.5 days''': Elbow appears.

'''16.5 days''': Fingers start to elongate.

'''17.5 days''': Knee becomes visible

'''19.5 days''': Hands and feet merge on the midline. Three segments of limbs become distinguished.

==='''Abdominal Wall Development'''===

'''9.5 days''': Abdominal wall is limited to the embryonic pedicle under the cardiac mass.

'''13.5 days''': First intestinal loops appear in the umbilical cord.

'''14.5 days – 17.5''': Rapid intestinal development in the cord.

'''15.5 days''': Abdominal vesicles can be observed.

'''16.5 days''': Cecal bud becomes present outside the abdomen

'''18.5 days''': Bowel returns to the abdominal cavity and umbilical ring closes.

==='''Cephalic Development'''===

'''9.5 days''': One cerebral vesicle can be seen. Pharyngeal arches as optic vesicle are present.

'''10.5 days''': Three arches are distinguished in the cephalic pole.

'''11.5 days''': Three cerebral vesicles present. Optic plate is distinguished.

'''12.5 days''': Face develops nasal, maxillar and mandibular buds. Lens vesicle is closed. Five cerebral vesicles exist.

'''14.5 days''': The ear becomes refined. Face can be distinguished from the brow.

'''18.5 days''': Eyelid appears, covering the eyes.

==Staging==

The following stages have been adapted from Beaudoin et al. (2003). Table 1 represents at each age its corresponding stage defined by the Carnegie classification

{| class="wikitable" style="text-align:center; width: 800px; height:1000px" border="1"
|+'''Table 1. Rabbit developmental stages using Carnegie classification'''

|- style="height:50px"
! '''Stage''' !! '''Days''' !! '''Event''' !! '''Image'''
|- style="width:200px"
! width="50" | 10
| width="50" | 8.5 || First somites appear, rostral neuropore closes
|- style="height:75px"
! 12
| 9.5 || Rostral limb bud, embryonic pedicle, caudal neuropore closes, one cerebral vesicle, pharyngeal arches, completion of optic vesicle
| [[file: 9.5new.JPG|100px]]
|- style="height:75px"
! 13
| 10.5 || Dosral C-shaped curvature, caudal limb bud, prominent cardiac swelling, four pharyngeal arches
| [[file: 10.5new.JPG|100px]]
|- style="height:75px"
! 14
| 11.5 || Three cerebral vesicles, optic plate, mesonephric ridge
|- style="height:75px"
! 15
| 12.5 || Hand plate, wheel ray limbs, lens vesicle closes, five cerebral vesicles, facial buds, vertebrae
| [[file: 12.5new.JPG|100px]]
|- style="height:75px"
! 16
| 13.5 || Foot plate, finger rays, prominent liver, intestinal loops, auricular hillocks
| [[file: 13.5new.JPG|100px]]
|- style="height:100px"
! 19
| 14.5 || Cuboidal body, trunk straightens, parallel limbs, toe rays, modeled face, visible auricle
| [[file: 14.5new.JPG|100px]]
|- style="height:75px"
! 20
| 15.5 || Elbow, fingers elongate, notches between toe rays
| [[file: 15.5new.JPG|100px]]
|- style="height:75px"
! 21-22
| 16.5 || Toes free, cecal bud in intestinal hernia
| [[file: 16.5new.JPG|100px]]
|- style="height:75px"
! 22-23
| 17.5 || Knee, neck, eyelids
| [[file: 17.5new.JPG|100px]]
|- style="height:75px"
! 23
| 18.5 || Hands and feet join at the midline, closure of abdominal wall, eyelids cover eyes
| [[file: 18.5new.JPG|100px]]
|-
| colspan="4" align="center"| Following this stage fetal appearance is completed, organogenesis is achieved
|}

==Genetics==

===Sequencing===
The National Human Genome Research Institute selected the European rabbit (Oryctolagus cuniculus) for whole genome sequencing to enhance their understanding of the human genome and use it experimentally for an animal model for human disease. (8)

The rabbit has been sequenced twice by The Broad Institute as part of the mammalian genome project. It is now currently undergoing 7 more sequencing projects. Its sequencing is made by the Whole Genome Shotgun (WGS) and assembly method. (9) This is when genomic DNA is sheared into small pieces of approximately 2000 base pairs which are then cloned into plasmids and sequenced on both strands. Once the contig fragments are read, realigned and reassembled by computer algorithms, it will give the overall sequence. (10) (11) The image below shows diagramatically how the two types of sequencing are different. The same techniques are used for sequencing the human genome (in 2003). [A contig is a set of overlapping DNA segments, derived from a single source of genetic material, from which the complete sequence may be deduced.

The whole genome shotgun (WGS) has serious gaps, yet the information has already proven useful for immunological as well as in silico studies. Deeper 7x coverage started in September 2007. The NCBI Rabbit Genome Resources site has links to searches for genes in the assemblies of the 2x WGS sequence at Ensembl and UCSC.(12) [http://www.broadinstitute.org/models/europeanrabbit/ Rabbit Genome Project]

[[File:WGS_sequencing.gif‎|center|800 px]]

===Genome===
The Rabbit genome was published by two groups (9)
# Lindblad-Toh,K., Chang,J.L., Gnerre,S., Clamp,M. and Lander,E.S. published their admission of 84024 bases on May 5th 2005 to The Broad Institute (USA) by shotgun sequencing
# Di Palma,F., Heiman,D., Young,S., Gnerre,S., Johnson,J., Lander,E.S. and Lindblad-Toh,K. published their admission of 84024 bases on August 3rd 2009 to The Broad Institute (USA) by shotgun sequencing.
The rabbit's genome is sequenced and on display in the Nucleotide Data Bank. It is too long to produce here. A link to the data bank is provided: [http://www.ncbi.nlm.nih.gov/nuccore/256946799/ Rabbit Genome from the Nucleotide Data Bank]

[[File:8cellembryo.jpg|thumb|Individual mitochondria (arrowheads) of an 8cell Rabbit embryo]]

The rabbit genome was sequenced in 2005 by Ensembl and managed to produce: (13)
* 2,076,044,328 supercontigs (ordered Contigs with gaps)
* 495 Known protein-coding genes
* 11,357 Projected protein-coding genes
* 2,343 RNA genes
* 212,581 Gene exons
* 20,311 Gene transcripts

For further research the taxonomy ID number for the Rabbit is: 9986 [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=9986&lvl=3&lin=f&keep=1&srchmode=1&unlock/ Taxonomy Data]

===Mitochondrial Genome===
The mitochondiral genome (mtDNA) of the rabbit was sequenced on November 14th 2006 with 17245 base pairs/nucleotides in circular form. Apparently the "length is not absolute due to the presence of different numbers of repeated motifs in the control region".
PMID 9653643

The image to the right shows the mitochondria during cell division and multiplication in embryo development.

=== Chromosomes ===
Over the years there have been various data suggesting the diploid chromosomal number for the rabbit may range from 22-42. However through recent research and an abundance of trials suggest that the rabbit does indeed have 22 different chromosome pairs existing in each cell of the rabbit. (16)(17) The sex chromosomes of the rabbit are of X-Y type convincingly (17). In a study in Bombay it confirmed that a rabbit has 2n = 44 chromosomes. There were 21 pairs of autosomes, out of which 1 to 6 were metacentric, 7 to 11 submetacentric, 12 to 17 subtelocentric and 18 to 21 acrocentric, plus the sex chromosomes. The image to the left shows a female rabbit with no chromosomal abnormalities. (19)

'''Comparison to human chromosome:'''

Rabbit chromosomes 12, 19 and X were found to be completely homologous to human chromosomes 6, 17 and X, respectively. All other human chromosomes were homologous to two or sometimes three rabbit chromosomes. (14) Chromosome 12 was shorter than chromosomes 13 and 14. (15) The image below illustrates the human chromosome (2n = 46).

[[File:Drawn chromosome.jpg|left|400 px]]

[[File:Karyotypehuman.gif|right|500 px]]

'''Abnormalities'''

These are generally more apparent during early embryo development in blastocysts from delayed fertilization. Some examples of abnormal development include cases of: (18)
* hypoploidy; 1 chromosome missing from a pair (2n = 43),
* double hypoploidy; 2 chromosomes missing from 2 different pairs (2n = 42),
* mosaicism (different chromosomal makeup in some cells).

Another study also found these abnormalities as well as: (19)
* autosomal trisomy (3 autosomes per pair),
* triploidy (extra set of chromsomes),
* mixoploidy (unequal number of chromosome sets in adjacent cells), and
* short arm deletion (deletion of parts of chromosomes).

A specific abnormality occurring in rabbits is the x-linked tremor. There is a mutation in exon 2 of the prteolipid-protein (PLP 1) gene, corresponding to the end of the first potential transmembrane domain of the protein. This disorder affects myelination of the central nervous system. OMIA ID:12 [http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=full_report&list_uids=100009169&log$=omiamaingene| Gene:100009169]

==Abnormal Development==

Abnormal embryological development is a vast field of study that has been the subject of recent research papers. Our investigation of abnormal development in rabbit embryology will focus on abnormalities commonly found in both rabbit and human embryos. We will explore the nature of these abnormalities in both humans and rabbits.

[[File:Normal v Abnormal.jpg|right|300 px|thumb|Brain MRI of patient with Hydrocephalus (left) compared to a normal brain (right). An obvious increase in ventricular size and a significant decrease in brain size is present.]]
[[File:Ventricle_Expansion.jpg|right|300 px|thumb|CSF accumulation in ventricles of brain increasing intracranial pressure.The pressure from the expanding ventricles force the brain and skull to grow outwards abnormally.]]

'''Hydrocephalus'''

Annually, one in every 1000 children born in Australia have hydrocephalus. Hydrocephalus occurs when excessive cerebrospinal fluid (CSF) accumulates in the brain and can result in severe disability and even death because the disorder can result in complete or near complete destruction of the cerebral cortex (22).

Children born with hydrocephalus typically exhibit abnormally large head circumference and bulging cranial fontanels as a result of increased intracranial pressure on the brain from the accumulating CSF (22,23). As CSF accumulates in the ventricles and CSF compartments of the brain, it expands forcing the brain to grow outward. The outward growing brain places pressure on the skull which in turn also grows outwards giving rise to an abnormally large head circumference and bulging cranial fontanels (22,24). It is generally acknowledged that children with hydrocephalus have mental retardation, often to the degree of being “vegetative” (24).

The serious consequences of this disease mean that much research is necessary to unearth methods of prevention and effective treatment. One of the modes of studying hydrocephalus is to use the rabbit experimental model where hydrocephalus can be induced in rabbit embryo’s. The injection of silicone oil into the cisterna magna of the brain is one way of inducing hydrocephalus in the rabbit embryo. The silicone oil obstructs the normal flow of CSF resulting in CSF accumulation in the brain leading to hydrocephalus (25). Another method of inducing hydrocephalus in rabbit embryo’s is by intentional vitamin A deprivation of pregnant dams. The vitamin A deficiency results in raised intracranial CSF pressure and aqueduct stenosis causing poor circulation of CSF leading to hydrocephalus (26,27). Although the exact function of vitamin A on brain development and CSF regulation is not fully understood, it is clear that Vitamin A has an important role in brain development and its normal functioning (27).
[[File:Rabbithhdrocephalus.jpg|center|300 px|thumb|Young rabbit with hydrocephalus caused by Vitamin A deficiency. Note the abnormally shaped cranium inflamed in appearance.]]

[[File:SpinabifidaMeningocele1.jpg|right|300 px|thumb|Spina Bifida Meningocele has characteristic damage to the meninges of the spinal cord which are pushed out through an opening in the vertebrae as a cyst filled with CSF.]]
[[File:SpinaBifidaMyelomeningocele.jpg|right|300 px|thumb|Spina Bifida Myelomeningocele is the most severe form of spinabifida where the damaged spinal cord protrudes out with damaged meninges as a cyst filled with CSF.]]
[[File:SpinaBifidaOcculta1.jpg|right|300 px|thumb|Spina Bifida Occulta is the least severe as the spinal cord and meninges are undamaged.]]

'''Spina Bifida'''

In Australia, the risk of spina bifida is 1 in every 500 pregnancies. Spina bifida is a type of neural tube defect where vertebrae (which normally cover and protect the spinal cord) are not completely formed but are divided resulting in the defective spinal cord and its coverings to protrude through the opening (28,29).

There are three main types of Spina Bifida differentiated by their characteristic features:

1)Spina Bifida Meningocele characterized by normal spinal cord, divided outer vertebrae and meninges surrounding the spinal cord protruding from the divided vertebrae as a cyst (1,28).

2)Spina Bifida Myelomeningocele characterized by split outer vertebrae with spinal cord and its meninges protruding from the divided vertebrae as a cyst. Commonly found at lumbar vertebral level (1,28,29).

3)Spina Bifida Occulta characterized unfused vertebral arches and exposed vertebral canal. Spinal cord and its meninges still located in vertebral canal (1,28).

All forms of spina bifida are potentially fatal and in those where the spinal cord is damaged severe consequence arise including and paralysis and loss of sensation at and below the level of damage spinal cord damage (29,33). There is a lot of Spina bifida research using rabbit models to test the effective methods of correcting spina bifida. The occurrence of natural spina bifida in rabbits is rare and for experimental purposes it can be surgically created in rabbit fetuses during gestation (31,32). The process involves aesthetical sedation of the maternal rabbit at day 22 of gestation; a midline laparotomy performed and the desired type of spina bifida lesion created on the exposed fetus using forceps. Different methods for correcting spina bifida can then be tested and its effectiveness analysed (30,33,34).
[[File:Rabbitspinabifida1.jpg|center|350 px|thumb|Rabbit newborn with Spina Bifida. Note the unfused, divided vertebrae and exposed spinal cord.]]

'''Brachydactylia & Acheiropodia'''

[[File:Malformation1.jpg|right|150 px|thumb|Acheiropodia in rabbit characterized by amputations of the limbs and extremities.]]

[[File:Rabbitmalformation3.jpg|left|150 px|thumb|X-Ray study of rabbit limbs with malformed phalanges due to Brachydactylia.]]

Brachydactylia and Acheiropodia are genetic disorders characterized by skeletal malformation of the hands and feet (36,36). In Brachydactylia, the malformations commonly involve abnormal shortening of fingers and toes due to poorly formed or absent bones (35). Acheiropodia is characterized by more severe skeletal malformations including bilateral amputations of the distal upper and lower extremities as well as aplasia of the hands and feet. Although it is not fatal, the individual endures a very difficult life without hands and feet (37).

The inheritance mechanism of this diseases can has been studied through experiment using rabbits. Rabbits with abnormal genes coding for Brachydactylia and Acheiropodia are selected and bred to produce offspring with the disease (36). Brachydactylia and Acheiropodia are autosomal recessive disorders which means that two copies of an abnormal gene must be present in the affected individual in order for the disease to develop. Thus, each parent passes an abnormal gene to the offspring (35,36). The process of the malformation progresses from genotype to phenotype; small deletions on the chromosomes produce abnormal genes, the abnormal genes are then passed down to the offspring, the offspring that inherits two of the abnormal genes is unable to code for the correct proteins and as a result, there is failure in normal development of limb extremities in the embryo phenotype (37,38).

==Current Embryology Research==

There is currently great excitement in research involving rabbits in the fields of transgenesis, cloning and stem cells. We shall explore research in these areas by discovering some of the techniques used and how they have been applied to the rabbit model.

[[File:Trans1.jpg|right|170 px]]
[[File:Trans2.jpg|right|170 px]]
[[File:Trans3.jpg|right|170 px]]
[[File:Trans4.jpg|right|170 px]]
[[File:Trans5.jpg|right|170 px]]

'''Transgenic rabbit'''

A transgenic organism is one whose genome also contains genes from another species (39). The aim of creating a transgenic organism is to obtain a favorable characteristic in the organism’s phenotype (41). This desired characteristic of phenotype is obtained by altering the organism’s normal genotype to include the gene from another species with the desired characteristic (39,40).

The production of a transgenic organism involves several steps summarized below:

1) The chromosome and the desired gene on it are identified in an organism (39).

2) The gene is isolated from its DNA strand. This involves “cutting” it out of its DNA strand using enzymes called restriction endonucleases. The restriction endonucleases cut DNA at specific site so the desired gene can be removed from the DNA strand. The cut ends are known as “sticky ends” (39,40).

3) Separate DNA sequences for regulation sometimes have to be added to ensure the gene will work (40).

4) The gene is then inserted with a promoter sequence into the fertilized egg cell of a new organism producing recombinant DNA (39,44). To do this, firstly the new organism’s cell DNA must first be cut and the desired gene incorporated into it. The same enzymes are used to cut the new organism’s cell DNA because the DNA stands from the two different organisms will form matching sticky ends that will be attracted to and connect with each other in a process is called “annealing” (39,40,44).

5) DNA ligases are sealing enzymes found in all living organisms that help make and repair DNA (39,40). The DNA ligases are added to the annealed DNA fragments to help strengthen the bonds of the new recombinant DNA. The recombinant DNA is now transferred into the new organism’s fertilized egg by microinjection (44).

6) As the embryo develops and the recombinant genetic code read, new proteins are synthesized which code for the new desired phenotype characteristic in the transgenic organism (39,40).

Transgenic rabbits can be created in the laboratory by gene microinjection into the fertilized rabbit oocyte (44). In April 2000, a transgenic rabbit named Alba was born containing a gene from a Pacific Northwest jellyfish. The gene which was injected into a fertilized albino rabbit oocyte allows the rabbit to synthesize the green fluorescent protein (GFP) that is characteristic of the Pacific Northwest jellyfish. When illuminated correctly, Alba glows a bright green (43,46).

Transgenic rabbits have important research purposes. Transgenic rabbits can be created to model retinal degeneration (44). Retinal degeneration is a common problem with aging and diseases such as diabetes, and frequently leads to complete blindness (42). A genetic retinal degeneration disease called retinitis pigmentosa (RP) is created in these rabbits by introducing the “Pro347Leu” mutation of the rhodopsin gene into fertilized rabbit eggs (43,44). As the rabbit grows, it develops the disease which becomes progressively worse (45).
The use of these transgenic rabbits ultimately leads to better understanding of the disease and more effective treatments (42). [[File:Transgenic rabbit.jpg|center|250 px|thumb|"Alba" A trangenic rabbit with a gene from a Pacific Northwest jellyfish that allows it to synthesize the green fluorescent protein (GFP) of the jellyfish.]]

[[File:Crabbit 1.jpg|right|170 px]]
[[File:Rabbit2.jpg|right|170 px]]
[[File:Rabbit3.jpg|right|170 px]]
[[File:Crabbit 4.jpg|right|170 px]]

'''Cloning'''

Cloning is a method of producing genetically identical organisms. The principle of cloning relies on “tricking” an egg cell to begin rapidly dividing into an embryo (39). In the normal fertilization process, two haploid sex cells unite to form a diploid zygote which begins rapidly dividing into an embryo (40). By replacing the haploid egg cell nucleus with a diploid somatic cell nucleus, the egg cell is tricked into thinking it is fertilized and hence begins rapidly dividing to form an embryo (39,40,41).

The process of cloning involves several steps summarized as the following using a rabbit example:

1) A somatic cell is obtained from a rabbit and the nucleus removed (39).

2) An egg cell is obtained from a donor rabbit and the nucleus of the egg cell removed using an enucleation needle. The cell is now called an enucleated egg cell (egg cell without a nucleus) (39,41).

3) The nucleus of the somatic cell is inserted into the enucleated egg cell (41).

4) The cell is now stimulated to divide by applying pulses of electric current (39).

5) The rapidly dividing cell develops in culture for a few days forming the early embryo (40,41).

6) The embryo is then implanted into the uterus of another rabbit similar to the egg cell donor. This rabbit is called the surrogate mother (40,41).

7) The embryo develops and the surrogate mother gives birth to a rabbit fetus with near identical genotype of the somatic cell donor (the small genomic difference is caused by the fetus obtaining mitochondrial DNA from the egg cell donor) (39,41).

The cloning of rabbits has been achieved by inserting the diploid nucleus of a rabbit fibroblast (the principal cells in connective tissue) into an enucleated oocyte (49). There is currently much focus on the creation of controversial but revolutionary interspecies hybrid embryos where the nucleus from a human somatic cells are implanted into an enucleated egg cell of another animal (50). The resulting embryo (known as a chimera) will be almost completely human genotype but will have genome from the other animal (48). In 2003, scientists at the Shanghai Second Medical University fused human cell with rabbit eggs creating the first human-rabbit hybrid using the nucleus transfer technique. The hybrid embryo developed in culture for a few days before it was destroyed and the stem cells harvested (47,48). The purpose of the research into creating hybrid embryos is to provide researchers with human stem cells for experimentation into cures for diseases such as cystic fibrosis, Alzheimer’s and Motor Neuron disease as human stem cell are difficult to obtain (50).

[[File:Rabbit clone.jpg|center|450 px|thumb|(A) Cloned rabbits (5 month old) from nuclear transfer technique. (B) The male rabbit whose fibroblasts were used as the nuclear donors. The cloned rabbits have almost identical genome to the male donor.]]

'''Stem Cells'''
[[File:HES.jpg|right|200 px|thumb|Human Embryonic Stem cell (hES).]]
[[File:Rabbit knee.jpg|right|200 px|thumb|Stem cell induced cartilage repair of knee in rabbit.]]

Stem cells are unspecialized cells which are able to continuously reproduce themselves and under appropriate conditions, differentiate into all the various specialized cells of the organism such as cardiac cells, neurons and blood cells (39,40). Adults have a small number of stem cells when compared to a developing embryo and the stem cell of an embryo more easily obtained (41). Human embryonic stem cells (hES) derived from the inner mass of the preimplantation blastocyst have the potential to differentiate into all cell types in the human body and thus are valued by researchers (50). However, due to ethical and political issues, the obtaining and experimentation on human embryonic stem cells is difficult and alternate means are needed as stem cell provides potentially new treatments for a range of diseases (54).

Rabbits can be used both in the obtaining of stem cell for experimentation and also as recipients of stem cells to cure diseases. The human-rabbit hybrid embryo provides a method of obtaining stem cells for experimentation and these stem cells possess many similar properties to human stem cells, including expression of surface markers, special growth requirements, capabilities of self renewal, formation of embryonic body and differentiation into cells of all three germ layers (53).

Stem cell experimentation on rabbits also focuses on transplanting stem cell into rabbits to treat specific diseases. A study at Zhejiang University where a research team transplanted human mesenchymal stem cell into New Zealand white rabbits with myocardial infarction recoded regeneration of vascular structure and improvement in cardiac function. The research team noted the potential of stem cells in differentiating into specialized cardiac cells when subjected to the specific conditions of the rabbit heart (52).

Another study at Hallym University tested the effectiveness of transplanting mesenchymal stem cells from New Zealand white rabbits into damaged cartilage in the knees of other New Zealand white rabbits. In the experiment, mesenchymal stem cells were obtained from the rabbit bone marrow and injected into the knees of other rabbits that had cartilage in their knees surgically damaged. The research team were able to conclude notable cartilage recovery in the rabbits with the mesenchymal stem cell injection and the potential of mesenchymal stem cells to differentiate into fibroblasts, adipoblasts, osteoblasts and chondroblasts (51,53).

The findings in stem cell experimentation with in rabbits yielded positive results and potentially opens a new field of research in the use of stem cell to treat a range of diseases in humans.

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# Bethesda (2009, September 23). Stem Cell Information. Retrieved from [http://stemcells.nih.gov]
# Cibelli, J. B. (2002). Principles of cloning Amsterdam. Academic Press
# European rabbit (oryctolagus cuniculus) Retrieved 9/21/2009, 2009, from http://www.feral.org.au/content/species/rabbit.cfm
# Warner, S. (2003). Inositol transport in preimplantation rabbit embryos: Effects of embryo stage, sodium, osmolality and metabolic inhibitors Reproduction, 125(4), 479-493.
# Derelanko, M. J. (2008). The toxicologist's pocket handbook, second edition Informa HealthCare
# Beaudoin, S., Barbet, P., & Bargy, F. (2003). Developmental stages in the rabbit embryo: Guidelines to choose an appropriate experimental model Fetal Diagnosis and Therapy, 18(6), 422-427.

==Glossary==

Anesthetic - A drug that causes temporary loss of bodily sensations

Aplasia - The absence or defective development of a tissue or organ

Blastocyst - A stage of embryo development that occurs about five days after fertilisation when the embryo contains quite a few cells

Caudal - Situated towards the inferior or posterior end of the body

Cephalic - Relating to the head

Cerebral Aqueduct - A canal filled with cerebrospinal fluid within the midbrain

Cerebral Cortex - The layer of unmyelinated neurons (the grey matter) forming the cortex of the cerebrum of the brain

Cerebro Spinal Fluid (CSF) - A watery fluid which flows in the cavities within the brain and around the surface of the brain and spinal cord

Chromosome - Microscopic carriers of genetic material, composed of deoxyribonucleic acid (DNA) and proteins and appearing as rods under a microscope

Cisterna Magna - is one of three principal openings in the subarachnoid space between the arachnoid and pia mater layers of the meninges surrounding the brain

Diploid - A full set of genetic material, consisting of paired chromosomes one chromosome from each parental set

Dorsal - Position towards the back

Fontanel - Membranous gap between the bones of the cranium in an infant or fetus

Genome - All genetic information, the entire genetic complement and all of the hereditary material possessed by an organism. Made up of both chromosomal genome (inside the nucleus of the cell in the familiar form of chromosomes) and mitochondrial genome (outside the nucleus in the cytoplasm of the cell, usually in the form of one round chromosome (the mitochondrial chromosome))

Genotype - The genetic makeup of an organism

Glucocorticoids - A class of steroid hormones that bind to the glucocorticoid receptor (GR), which is present in almost every vertebrate

Haploid - A single set of chromosomes (half the full set of genetic material)

Laparotomy- Surgical incision into the abdominal wall; often done to examine abdominal organs

Ligases - Group of enzymes that catalyze the binding of two molecules

Oocyte - A female gametocyte that develops into an ovum after two meiotic divisions

Phenotype - The observable traits or characteristics of an organism, for example hair color, weight, or the presence or absence of a disease.

Pronuclear - Haploid nucleus before fusion of nuclei in fertilisation

Restriction Endonucleases - Enzymes that recognize and cleave specific DNA sequences, generating either blunt or single-stranded (sticky) ends

Retina - The thin layer of cells at the back of the eyeball where light is converted into neural signals sent to the brain

Rostral - Situated toward the oral and nasal region

Somite - Blocks of mesoderm on either side of the notochord and neural tube during development of the vertebrate embryo. Develop into muscles and vertebrae

Stenosis - Abnormal narrowing of a bodily canal or passageway

Weaning - Young become accustom to nourishment other than suckling

==Links to Research Laboratories and Researchers==

1) Transgenic lab: [http://www.dnavision.be/index.php]

Involved in development of transgenic organisms, DNA construction and phenotype analysis.

2) World Rabbit Science Association: (WRSA) [http://world-rabbit-science.com]

International Association where researchers exchange knowledge and encourage teaching, scientific research, practical experimentation, the collection and publication of statistics and documents relating to the rabbit. Even have their own journal called “World Rabbit Science”

Website provides contact with researchers, professors and veterinarians working with rabbits.

Example: Dr. Myriam Kaplan-Pasternak, Doctorate Veterinary Medicine, University of California, myriamsemail@gmail.com

3) American Veterinary Medical Association [http://www.avma.org]

The American Veterinary Medical Association (AVMA), established in 1863, is a not-for-profit association representing more than 78,000 veterinarians working in private and corporate practice, government, industry, academia, and uniformed services. Excellent website into animal research and has a range of veterinary journals.

{{Template:Projects09}}
[[Category:Rabbit]]
[[File:Example.jpg]]

2009 Group Project 1

2009-10-14T12:03:25Z

Z3185685: /* Introduction */

[[File:Rabbits.png|right|400 px]]

== '''THE RABBIT (ORYCTOLAGUS CUNICULUS)''' ==

==Introduction==

[[File:Isidro_Martinez.jpg‎|left|175 px]]

Several characteristics of the rabbit make it an excellent model for study. This will be further explored in the history section of this page. Many studies have resulted in the development and improvement of various micro-manipulation techniques such as the production of transgenic rabbits. The rabbit is an appropriate animal model as the results from many experiments are significant to that of other mammals, including humans. (55)

A rabbits potential for reproduction is high, breeding from the early stages of 3 to 4 months of age. A mature female rabbit can be pregnant from 6 to 8 months in a year, producing up to 30 to 40 young in this time. (56)

==History of Model Use==

'''WHY are we using rabbits?'''

ADVANTAGES
*Provides repeatability of animal model studies
*Large enough for single samples
*Many stocks/strains as animal models
*Easily managed
*Quality of immunologic products
*Ease of reproductive control

DISADVANTAGES
*Most colonies are a storehouse of diseases
*Extremely variable to responses to general anesthetics

'''Brief timeline of rabbit embryo model use'''

*1672- de Graaf found the Graffian follicle.
*1890- Walter Heape succeeded first mammalian embryo transfer
*1906- FT Lewis discovered the development of the lymphatic system in rabbit embryos.
*1941- Dr. Pincus succeeded in keeping rabbit embryos developing in the test
*1968- Edwards and Gardner successfully performed the first known embryo biopsy on rabbit embryos

=== Regnier de Graaf (1641–1673) ===
[[image:Ovary_Graaf.jpg|thumb|250px|left|drawing of ovary]]
[[File:Regnier de Graaf.jpg|right]]

'''Discovery of the Graafian Follicles'''

In 1672 de Graaf published ''The Generative Organs of Women'', which was primarily a study of development in the rabbit. When de Graaf discovered large, round welling on the ovaries of rabbits, he assumed they were mammalian eggs. De Graaf also described the corpus luteum.

He summarised the previous works from anatomists, but unable to experience the amazing benefits made by microscopy.
But Antonie van Leeuwenhoek (A microbiologist, 1632 - 1723) argued that the structures now known as Graafian follicles could not be eggs. Haller suggested that the egg might be formed by the coagulation of the fluid within the Graafian follicle. De Graaf noted that the “egg” did not contain a tiny embryo, but he thought it did contain the “germ” of the future organism. (3)

=== Walter Heape (1855-1928) ===
'''First case of embryo transfer experiments'''

On 27 April 1890, Walter Heape (a professor and physician at the University of Cambridge, England) transferred rabbit embryos from one mother to another. (7) One rabbit mother became pregnant and delivered young from the transferred embryos. This was the first mammalian embryo transfer experiment to be successfully completed. His embryo transfer work in perspective as it relates to other contributions of this pioneer in reproductive biology.(7)

In 1891, Walter Heape had been conducting research on reproduction in numerous animal species. Working with two species of rabbits, he flushed embryos from the rabbit fallopian tubes of one breed (Angora) and placed them into the uterus of a recently mated Belgian hare. In the resulting litter, there were 4 Belgians and 2 Angoras. Heape proved that it was possible to take preimplantation embryos and transfer them to a gestational carrier without affecting their development.(7)

===Dr. Gregory Goodwin Pincus (1903-1967) ===

'''Contraceptive pill'''

Dr. Pincus began studying hormonal biology and steroidal hormones early in his career. His first breakthrough came when he was able to produce in vitro fertilization in rabbits (by using chemicals) in 1934. Throughout their hormonal contraceptive research Pincus, along with reproductive physiologist Min Chueh Chang, found out progesterone would act as an inhibitor to ovulation. They co-invented the combined oral contraceptive pill.[2][6]

===Genetic Diagnosis===
In 1968, Robert Edwards and David Gardner reported the successful sexing of rabbit blastocysts, setting the first steps towards PGD (Preimplantation Genetic Diagnosis). It was not until the 1980s that human IVF was fully developed, which coincided with the breakthrough of the highly sensitive polymerase chain reaction (PCR) technology. Handyside and collaborators' first successful attempts at testing were in October 1989 with the first births in 1990 though the preliminary experiments had been published some years earlier. In these first cases, PCR was used for sex determination for patients carrying X-linked diseases.(12)

==Timeline of Embryo Development==

The following is a timeline, adapted from Cibelli (2002), of the main events of preimplantation development in rabbits. The time is measured in hours post-mating and shows the embryo stage (cell number) in each time scale.

[[File:Morula1.JPG|right|200 px|thumb|A day 2 early morula]]

'''12-14 hours:''' Oocyte; Fertilization

'''18-20 hours:''' Zygote; Pronuclear formation

'''24-26 hours:''' Two cell

'''30-32 hours:''' Four cell

'''38-40 hours:''' Eight cell; Maternal-zygotic transition

'''46-48 hours:''' Sixteen cell

'''54-56 hours:''' Morula (32 cell); Compaction and transport to uterus

'''64-66 hours:''' Compact morula (64 cell); Morula-blastocyst transition

'''76-78 hours:''' Early blastocyst (128 cell)

'''84-86 hours:''' Expanded blastocyst (256 cell); Blastocoels expansion

'''94-96 hours:''' Hatched blastocyst (512 cell); Hatching

The following shows a diagrammatic representation of the relative sizes of rabbit embryos. The sizes do not include the embryonic coverings such as the zona pellucida and mucin coat. This diagram has been adapted from Warner (2003).

[[File:Sizes.JPG]]

The following timelines show a comparison of the developmental stages between human and rabbit embryos. They have been adapted from Derelanko (2008). "The similarities of this developmental pattern in humans and rabbits, suggests that the same growth increment is required to achieve the same stage. The main difference observed between human rabbit gestational duration is due to the fetal growth phase. The reason for this may be due to birth weight, lifetime and the neural complexity of the species." (59)

[[File:Timeline_rabbit.JPG]]

The following timelines have been adapted from a study carried out by Beaudoin et al. on the development of rabbit embryos.

==='''Body Form'''===

'''8.5 days''': Embryo thickens. First somites appear. Rostral neuropore closes. Caudal neuropore remains open

'''9.5 days''': Dorsal curvature begins. Cardiac mass bulges under cephalic pole.

'''10.5 - 13.5 days''': Dorsal curvature increases. Body thickens. Softening of the cephalic domination straightens the embryo.

'''17.5 days''': Neck becomes visible.

==='''Limb Development'''===

''' 9.5 days''': Rostral limb bud appears

'''10.5 days''': Caudal limb bud appears

'''12.5 days''': Hand plate becomes present. Limbs become disposed.

'''13.5 days''': Foot plate and finger rays become visible.

'''14.5 days''': Rostral and caudal limbs become parallel.

'''15.5 days''': Elbow appears.

'''16.5 days''': Fingers start to elongate.

'''17.5 days''': Knee becomes visible

'''19.5 days''': Hands and feet merge on the midline. Three segments of limbs become distinguished.

==='''Abdominal Wall Development'''===

'''9.5 days''': Abdominal wall is limited to the embryonic pedicle under the cardiac mass.

'''13.5 days''': First intestinal loops appear in the umbilical cord.

'''14.5 days – 17.5''': Rapid intestinal development in the cord.

'''15.5 days''': Abdominal vesicles can be observed.

'''16.5 days''': Cecal bud becomes present outside the abdomen

'''18.5 days''': Bowel returns to the abdominal cavity and umbilical ring closes.

==='''Cephalic Development'''===

'''9.5 days''': One cerebral vesicle can be seen. Pharyngeal arches as optic vesicle are present.

'''10.5 days''': Three arches are distinguished in the cephalic pole.

'''11.5 days''': Three cerebral vesicles present. Optic plate is distinguished.

'''12.5 days''': Face develops nasal, maxillar and mandibular buds. Lens vesicle is closed. Five cerebral vesicles exist.

'''14.5 days''': The ear becomes refined. Face can be distinguished from the brow.

'''18.5 days''': Eyelid appears, covering the eyes.

==Staging==

The following stages have been adapted from Beaudoin et al. (2003). Table 1 represents at each age its corresponding stage defined by the Carnegie classification

{| class="wikitable" style="text-align:center; width: 800px; height:1000px" border="1"
|+'''Table 1. Rabbit developmental stages using Carnegie classification'''

|- style="height:50px"
! '''Stage''' !! '''Days''' !! '''Event''' !! '''Image'''
|- style="width:200px"
! width="50" | 10
| width="50" | 8.5 || First somites appear, rostral neuropore closes
|- style="height:75px"
! 12
| 9.5 || Rostral limb bud, embryonic pedicle, caudal neuropore closes, one cerebral vesicle, pharyngeal arches, completion of optic vesicle
| [[file: 9.5new.JPG|100px]]
|- style="height:75px"
! 13
| 10.5 || Dosral C-shaped curvature, caudal limb bud, prominent cardiac swelling, four pharyngeal arches
| [[file: 10.5new.JPG|100px]]
|- style="height:75px"
! 14
| 11.5 || Three cerebral vesicles, optic plate, mesonephric ridge
|- style="height:75px"
! 15
| 12.5 || Hand plate, wheel ray limbs, lens vesicle closes, five cerebral vesicles, facial buds, vertebrae
| [[file: 12.5new.JPG|100px]]
|- style="height:75px"
! 16
| 13.5 || Foot plate, finger rays, prominent liver, intestinal loops, auricular hillocks
| [[file: 13.5new.JPG|100px]]
|- style="height:100px"
! 19
| 14.5 || Cuboidal body, trunk straightens, parallel limbs, toe rays, modeled face, visible auricle
| [[file: 14.5new.JPG|100px]]
|- style="height:75px"
! 20
| 15.5 || Elbow, fingers elongate, notches between toe rays
| [[file: 15.5new.JPG|100px]]
|- style="height:75px"
! 21-22
| 16.5 || Toes free, cecal bud in intestinal hernia
| [[file: 16.5new.JPG|100px]]
|- style="height:75px"
! 22-23
| 17.5 || Knee, neck, eyelids
| [[file: 17.5new.JPG|100px]]
|- style="height:75px"
! 23
| 18.5 || Hands and feet join at the midline, closure of abdominal wall, eyelids cover eyes
| [[file: 18.5new.JPG|100px]]
|-
| colspan="4" align="center"| Following this stage fetal appearance is completed, organogenesis is achieved
|}

==Genetics==

===Sequencing===
The National Human Genome Research Institute selected the European rabbit (Oryctolagus cuniculus) for whole genome sequencing to enhance their understanding of the human genome and use it experimentally for an animal model for human disease. (8)

The rabbit has been sequenced twice by The Broad Institute as part of the mammalian genome project. It is now currently undergoing 7 more sequencing projects. Its sequencing is made by the Whole Genome Shotgun (WGS) and assembly method. (9) This is when genomic DNA is sheared into small pieces of approximately 2000 base pairs which are then cloned into plasmids and sequenced on both strands. Once the contig fragments are read, realigned and reassembled by computer algorithms, it will give the overall sequence. (10) (11) The image below shows diagramatically how the two types of sequencing are different. The same techniques are used for sequencing the human genome (in 2003). [A contig is a set of overlapping DNA segments, derived from a single source of genetic material, from which the complete sequence may be deduced.

The whole genome shotgun (WGS) has serious gaps, yet the information has already proven useful for immunological as well as in silico studies. Deeper 7x coverage started in September 2007. The NCBI Rabbit Genome Resources site has links to searches for genes in the assemblies of the 2x WGS sequence at Ensembl and UCSC.(12) [http://www.broadinstitute.org/models/europeanrabbit/ Rabbit Genome Project]

[[File:WGS_sequencing.gif‎|center|800 px]]

===Genome===
The Rabbit genome was published by two groups (9)
# Lindblad-Toh,K., Chang,J.L., Gnerre,S., Clamp,M. and Lander,E.S. published their admission of 84024 bases on May 5th 2005 to The Broad Institute (USA) by shotgun sequencing
# Di Palma,F., Heiman,D., Young,S., Gnerre,S., Johnson,J., Lander,E.S. and Lindblad-Toh,K. published their admission of 84024 bases on August 3rd 2009 to The Broad Institute (USA) by shotgun sequencing.
The rabbit's genome is sequenced and on display in the Nucleotide Data Bank. It is too long to produce here. A link to the data bank is provided: [http://www.ncbi.nlm.nih.gov/nuccore/256946799/ Rabbit Genome from the Nucleotide Data Bank]

[[File:8cellembryo.jpg|thumb|Individual mitochondria (arrowheads) of an 8cell Rabbit embryo]]

The rabbit genome was sequenced in 2005 by Ensembl and managed to produce: (13)
* 2,076,044,328 supercontigs (ordered Contigs with gaps)
* 495 Known protein-coding genes
* 11,357 Projected protein-coding genes
* 2,343 RNA genes
* 212,581 Gene exons
* 20,311 Gene transcripts

For further research the taxonomy ID number for the Rabbit is: 9986 [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=9986&lvl=3&lin=f&keep=1&srchmode=1&unlock/ Taxonomy Data]

===Mitochondrial Genome===
The mitochondiral genome (mtDNA) of the rabbit was sequenced on November 14th 2006 with 17245 base pairs/nucleotides in circular form. Apparently the "length is not absolute due to the presence of different numbers of repeated motifs in the control region".
PMID 9653643

The image to the right shows the mitochondria during cell division and multiplication in embryo development.

=== Chromosomes ===
Over the years there have been various data suggesting the diploid chromosomal number for the rabbit may range from 22-42. However through recent research and an abundance of trials suggest that the rabbit does indeed have 22 different chromosome pairs existing in each cell of the rabbit. (16)(17) The sex chromosomes of the rabbit are of X-Y type convincingly (17). In a study in Bombay it confirmed that a rabbit has 2n = 44 chromosomes. There were 21 pairs of autosomes, out of which 1 to 6 were metacentric, 7 to 11 submetacentric, 12 to 17 subtelocentric and 18 to 21 acrocentric, plus the sex chromosomes. The image to the left shows a female rabbit with no chromosomal abnormalities. (19)

'''Comparison to human chromosome:'''

Rabbit chromosomes 12, 19 and X were found to be completely homologous to human chromosomes 6, 17 and X, respectively. All other human chromosomes were homologous to two or sometimes three rabbit chromosomes. (14) Chromosome 12 was shorter than chromosomes 13 and 14. (15) The image below illustrates the human chromosome (2n = 46).

[[File:Drawn chromosome.jpg|left|400 px]]

[[File:Karyotypehuman.gif|right|500 px]]

'''Abnormalities'''

These are generally more apparent during early embryo development in blastocysts from delayed fertilization. Some examples of abnormal development include cases of: (18)
* hypoploidy; 1 chromosome missing from a pair (2n = 43),
* double hypoploidy; 2 chromosomes missing from 2 different pairs (2n = 42),
* mosaicism (different chromosomal makeup in some cells).

Another study also found these abnormalities as well as: (19)
* autosomal trisomy (3 autosomes per pair),
* triploidy (extra set of chromsomes),
* mixoploidy (unequal number of chromosome sets in adjacent cells), and
* short arm deletion (deletion of parts of chromosomes).

A specific abnormality occurring in rabbits is the x-linked tremor. There is a mutation in exon 2 of the prteolipid-protein (PLP 1) gene, corresponding to the end of the first potential transmembrane domain of the protein. This disorder affects myelination of the central nervous system. OMIA ID:12 [http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=full_report&list_uids=100009169&log$=omiamaingene| Gene:100009169]

==Abnormal Development==

Abnormal embryological development is a vast field of study that has been the subject of recent research papers. Our investigation of abnormal development in rabbit embryology will focus on abnormalities commonly found in both rabbit and human embryos. We will explore the nature of these abnormalities in both humans and rabbits.

[[File:Normal v Abnormal.jpg|right|300 px|thumb|Brain MRI of patient with Hydrocephalus (left) compared to a normal brain (right). An obvious increase in ventricular size and a significant decrease in brain size is present.]]
[[File:Ventricle_Expansion.jpg|right|300 px|thumb|CSF accumulation in ventricles of brain increasing intracranial pressure.The pressure from the expanding ventricles force the brain and skull to grow outwards abnormally.]]

'''Hydrocephalus'''

Annually, one in every 1000 children born in Australia have hydrocephalus. Hydrocephalus occurs when excessive cerebrospinal fluid (CSF) accumulates in the brain and can result in severe disability and even death because the disorder can result in complete or near complete destruction of the cerebral cortex (22).

Children born with hydrocephalus typically exhibit abnormally large head circumference and bulging cranial fontanels as a result of increased intracranial pressure on the brain from the accumulating CSF (22,23). As CSF accumulates in the ventricles and CSF compartments of the brain, it expands forcing the brain to grow outward. The outward growing brain places pressure on the skull which in turn also grows outwards giving rise to an abnormally large head circumference and bulging cranial fontanels (22,24). It is generally acknowledged that children with hydrocephalus have mental retardation, often to the degree of being “vegetative” (24).

The serious consequences of this disease mean that much research is necessary to unearth methods of prevention and effective treatment. One of the modes of studying hydrocephalus is to use the rabbit experimental model where hydrocephalus can be induced in rabbit embryo’s. The injection of silicone oil into the cisterna magna of the brain is one way of inducing hydrocephalus in the rabbit embryo. The silicone oil obstructs the normal flow of CSF resulting in CSF accumulation in the brain leading to hydrocephalus (25). Another method of inducing hydrocephalus in rabbit embryo’s is by intentional vitamin A deprivation of pregnant dams. The vitamin A deficiency results in raised intracranial CSF pressure and aqueduct stenosis causing poor circulation of CSF leading to hydrocephalus (26,27). Although the exact function of vitamin A on brain development and CSF regulation is not fully understood, it is clear that Vitamin A has an important role in brain development and its normal functioning (27).
[[File:Rabbithhdrocephalus.jpg|center|300 px|thumb|Young rabbit with hydrocephalus caused by Vitamin A deficiency. Note the abnormally shaped cranium inflamed in appearance.]]

[[File:SpinabifidaMeningocele1.jpg|right|300 px|thumb|Spina Bifida Meningocele has characteristic damage to the meninges of the spinal cord which are pushed out through an opening in the vertebrae as a cyst filled with CSF.]]
[[File:SpinaBifidaMyelomeningocele.jpg|right|300 px|thumb|Spina Bifida Myelomeningocele is the most severe form of spinabifida where the damaged spinal cord protrudes out with damaged meninges as a cyst filled with CSF.]]
[[File:SpinaBifidaOcculta1.jpg|right|300 px|thumb|Spina Bifida Occulta is the least severe as the spinal cord and meninges are undamaged.]]

'''Spina Bifida'''

In Australia, the risk of spina bifida is 1 in every 500 pregnancies. Spina bifida is a type of neural tube defect where vertebrae (which normally cover and protect the spinal cord) are not completely formed but are divided resulting in the defective spinal cord and its coverings to protrude through the opening (28,29).

There are three main types of Spina Bifida differentiated by their characteristic features:

1)Spina Bifida Meningocele characterized by normal spinal cord, divided outer vertebrae and meninges surrounding the spinal cord protruding from the divided vertebrae as a cyst (1,28).

2)Spina Bifida Myelomeningocele characterized by split outer vertebrae with spinal cord and its meninges protruding from the divided vertebrae as a cyst. Commonly found at lumbar vertebral level (1,28,29).

3)Spina Bifida Occulta characterized unfused vertebral arches and exposed vertebral canal. Spinal cord and its meninges still located in vertebral canal (1,28).

All forms of spina bifida are potentially fatal and in those where the spinal cord is damaged severe consequence arise including and paralysis and loss of sensation at and below the level of damage spinal cord damage (29,33). There is a lot of Spina bifida research using rabbit models to test the effective methods of correcting spina bifida. The occurrence of natural spina bifida in rabbits is rare and for experimental purposes it can be surgically created in rabbit fetuses during gestation (31,32). The process involves aesthetical sedation of the maternal rabbit at day 22 of gestation; a midline laparotomy performed and the desired type of spina bifida lesion created on the exposed fetus using forceps. Different methods for correcting spina bifida can then be tested and its effectiveness analysed (30,33,34).
[[File:Rabbitspinabifida1.jpg|center|350 px|thumb|Rabbit newborn with Spina Bifida. Note the unfused, divided vertebrae and exposed spinal cord.]]

'''Brachydactylia & Acheiropodia'''

[[File:Malformation1.jpg|right|150 px|thumb|Acheiropodia in rabbit characterized by amputations of the limbs and extremities.]]

[[File:Rabbitmalformation3.jpg|left|150 px|thumb|X-Ray study of rabbit limbs with malformed phalanges due to Brachydactylia.]]

Brachydactylia and Acheiropodia are genetic disorders characterized by skeletal malformation of the hands and feet (36,36). In Brachydactylia, the malformations commonly involve abnormal shortening of fingers and toes due to poorly formed or absent bones (35). Acheiropodia is characterized by more severe skeletal malformations including bilateral amputations of the distal upper and lower extremities as well as aplasia of the hands and feet. Although it is not fatal, the individual endures a very difficult life without hands and feet (37).

The inheritance mechanism of this diseases can has been studied through experiment using rabbits. Rabbits with abnormal genes coding for Brachydactylia and Acheiropodia are selected and bred to produce offspring with the disease (36). Brachydactylia and Acheiropodia are autosomal recessive disorders which means that two copies of an abnormal gene must be present in the affected individual in order for the disease to develop. Thus, each parent passes an abnormal gene to the offspring (35,36). The process of the malformation progresses from genotype to phenotype; small deletions on the chromosomes produce abnormal genes, the abnormal genes are then passed down to the offspring, the offspring that inherits two of the abnormal genes is unable to code for the correct proteins and as a result, there is failure in normal development of limb extremities in the embryo phenotype (37,38).

==Current Embryology Research==

There is currently great excitement in research involving rabbits in the fields of transgenesis, cloning and stem cells. We shall explore research in these areas by discovering some of the techniques used and how they have been applied to the rabbit model.

[[File:Trans1.jpg|right|170 px]]
[[File:Trans2.jpg|right|170 px]]
[[File:Trans3.jpg|right|170 px]]
[[File:Trans4.jpg|right|170 px]]
[[File:Trans5.jpg|right|170 px]]

'''Transgenic rabbit'''

A transgenic organism is one whose genome also contains genes from another species (39). The aim of creating a transgenic organism is to obtain a favorable characteristic in the organism’s phenotype (41). This desired characteristic of phenotype is obtained by altering the organism’s normal genotype to include the gene from another species with the desired characteristic (39,40).

The production of a transgenic organism involves several steps summarized below:

1) The chromosome and the desired gene on it are identified in an organism (39).

2) The gene is isolated from its DNA strand. This involves “cutting” it out of its DNA strand using enzymes called restriction endonucleases. The restriction endonucleases cut DNA at specific site so the desired gene can be removed from the DNA strand. The cut ends are known as “sticky ends” (39,40).

3) Separate DNA sequences for regulation sometimes have to be added to ensure the gene will work (40).

4) The gene is then inserted with a promoter sequence into the fertilized egg cell of a new organism producing recombinant DNA (39,44). To do this, firstly the new organism’s cell DNA must first be cut and the desired gene incorporated into it. The same enzymes are used to cut the new organism’s cell DNA because the DNA stands from the two different organisms will form matching sticky ends that will be attracted to and connect with each other in a process is called “annealing” (39,40,44).

5) DNA ligases are sealing enzymes found in all living organisms that help make and repair DNA (39,40). The DNA ligases are added to the annealed DNA fragments to help strengthen the bonds of the new recombinant DNA. The recombinant DNA is now transferred into the new organism’s fertilized egg by microinjection (44).

6) As the embryo develops and the recombinant genetic code read, new proteins are synthesized which code for the new desired phenotype characteristic in the transgenic organism (39,40).

Transgenic rabbits can be created in the laboratory by gene microinjection into the fertilized rabbit oocyte (44). In April 2000, a transgenic rabbit named Alba was born containing a gene from a Pacific Northwest jellyfish. The gene which was injected into a fertilized albino rabbit oocyte allows the rabbit to synthesize the green fluorescent protein (GFP) that is characteristic of the Pacific Northwest jellyfish. When illuminated correctly, Alba glows a bright green (43,46).

Transgenic rabbits have important research purposes. Transgenic rabbits can be created to model retinal degeneration (44). Retinal degeneration is a common problem with aging and diseases such as diabetes, and frequently leads to complete blindness (42). A genetic retinal degeneration disease called retinitis pigmentosa (RP) is created in these rabbits by introducing the “Pro347Leu” mutation of the rhodopsin gene into fertilized rabbit eggs (43,44). As the rabbit grows, it develops the disease which becomes progressively worse (45).
The use of these transgenic rabbits ultimately leads to better understanding of the disease and more effective treatments (42). [[File:Transgenic rabbit.jpg|center|250 px|thumb|"Alba" A trangenic rabbit with a gene from a Pacific Northwest jellyfish that allows it to synthesize the green fluorescent protein (GFP) of the jellyfish.]]

[[File:Crabbit 1.jpg|right|170 px]]
[[File:Rabbit2.jpg|right|170 px]]
[[File:Rabbit3.jpg|right|170 px]]
[[File:Crabbit 4.jpg|right|170 px]]

'''Cloning'''

Cloning is a method of producing genetically identical organisms. The principle of cloning relies on “tricking” an egg cell to begin rapidly dividing into an embryo (39). In the normal fertilization process, two haploid sex cells unite to form a diploid zygote which begins rapidly dividing into an embryo (40). By replacing the haploid egg cell nucleus with a diploid somatic cell nucleus, the egg cell is tricked into thinking it is fertilized and hence begins rapidly dividing to form an embryo (39,40,41).

The process of cloning involves several steps summarized as the following using a rabbit example:

1) A somatic cell is obtained from a rabbit and the nucleus removed (39).

2) An egg cell is obtained from a donor rabbit and the nucleus of the egg cell removed using an enucleation needle. The cell is now called an enucleated egg cell (egg cell without a nucleus) (39,41).

3) The nucleus of the somatic cell is inserted into the enucleated egg cell (41).

4) The cell is now stimulated to divide by applying pulses of electric current (39).

5) The rapidly dividing cell develops in culture for a few days forming the early embryo (40,41).

6) The embryo is then implanted into the uterus of another rabbit similar to the egg cell donor. This rabbit is called the surrogate mother (40,41).

7) The embryo develops and the surrogate mother gives birth to a rabbit fetus with near identical genotype of the somatic cell donor (the small genomic difference is caused by the fetus obtaining mitochondrial DNA from the egg cell donor) (39,41).

The cloning of rabbits has been achieved by inserting the diploid nucleus of a rabbit fibroblast (the principal cells in connective tissue) into an enucleated oocyte (49). There is currently much focus on the creation of controversial but revolutionary interspecies hybrid embryos where the nucleus from a human somatic cells are implanted into an enucleated egg cell of another animal (50). The resulting embryo (known as a chimera) will be almost completely human genotype but will have genome from the other animal (48). In 2003, scientists at the Shanghai Second Medical University fused human cell with rabbit eggs creating the first human-rabbit hybrid using the nucleus transfer technique. The hybrid embryo developed in culture for a few days before it was destroyed and the stem cells harvested (47,48). The purpose of the research into creating hybrid embryos is to provide researchers with human stem cells for experimentation into cures for diseases such as cystic fibrosis, Alzheimer’s and Motor Neuron disease as human stem cell are difficult to obtain (50).

[[File:Rabbit clone.jpg|center|450 px|thumb|(A) Cloned rabbits (5 month old) from nuclear transfer technique. (B) The male rabbit whose fibroblasts were used as the nuclear donors. The cloned rabbits have almost identical genome to the male donor.]]

'''Stem Cells'''
[[File:HES.jpg|right|200 px|thumb|Human Embryonic Stem cell (hES).]]
[[File:Rabbit knee.jpg|right|200 px|thumb|Stem cell induced cartilage repair of knee in rabbit.]]

Stem cells are unspecialized cells which are able to continuously reproduce themselves and under appropriate conditions, differentiate into all the various specialized cells of the organism such as cardiac cells, neurons and blood cells (39,40). Adults have a small number of stem cells when compared to a developing embryo and the stem cell of an embryo more easily obtained (41). Human embryonic stem cells (hES) derived from the inner mass of the preimplantation blastocyst have the potential to differentiate into all cell types in the human body and thus are valued by researchers (50). However, due to ethical and political issues, the obtaining and experimentation on human embryonic stem cells is difficult and alternate means are needed as stem cell provides potentially new treatments for a range of diseases (54).

Rabbits can be used both in the obtaining of stem cell for experimentation and also as recipients of stem cells to cure diseases. The human-rabbit hybrid embryo provides a method of obtaining stem cells for experimentation and these stem cells possess many similar properties to human stem cells, including expression of surface markers, special growth requirements, capabilities of self renewal, formation of embryonic body and differentiation into cells of all three germ layers (53).

Stem cell experimentation on rabbits also focuses on transplanting stem cell into rabbits to treat specific diseases. A study at Zhejiang University where a research team transplanted human mesenchymal stem cell into New Zealand white rabbits with myocardial infarction recoded regeneration of vascular structure and improvement in cardiac function. The research team noted the potential of stem cells in differentiating into specialized cardiac cells when subjected to the specific conditions of the rabbit heart (52).

Another study at Hallym University tested the effectiveness of transplanting mesenchymal stem cells from New Zealand white rabbits into damaged cartilage in the knees of other New Zealand white rabbits. In the experiment, mesenchymal stem cells were obtained from the rabbit bone marrow and injected into the knees of other rabbits that had cartilage in their knees surgically damaged. The research team were able to conclude notable cartilage recovery in the rabbits with the mesenchymal stem cell injection and the potential of mesenchymal stem cells to differentiate into fibroblasts, adipoblasts, osteoblasts and chondroblasts (51,53).

The findings in stem cell experimentation with in rabbits yielded positive results and potentially opens a new field of research in the use of stem cell to treat a range of diseases in humans.

==References==

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# E.Horne Craigie, University of Toronto Press 1948, Bensley's Practical Anatomy of the Rabbit 8th Edition
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# Jocelyn HD, Setchell BP (December 1972). "Regnier de Graaf on the human reproductive organs. An annotated translation of Tractatus de Virorum Organis Generationi Inservientibus (1668) and De Mulierub Organis Generationi Inservientibus Tractatus Novus (1962)". Journal of Reproduction and Fertility. Supplement 17: 1–222.
# Jay, V. (2000). "A portrait in history. The legacy of Reinier de Graaf". Archives of Pathology & Laboratory Medicine 124(8): 1115–6.
# Lois N Magner. "A history of the Life Sciences" 3rd edition
# J. D. Biggers. (1991). Walter Heape, FRS: a pioneer in reproductive biology.Centenary of his embryo transfer experiments Laboratory of Human Reproduction and Reproductive Biology, and Department of Cellular and Molecular Physiology, Harvard Medical School, Boston, MA 02115, USA
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# Campbell, M. A. (2002). ''Sequencing Whole Genomes: Hierarchical Shotgun Sequencing v. Shotgun Sequencing'' Retrieved August 31, 2009, from [http://www.bio.davidson.edu/courses/GENOMICS/method/shotgun.html/ Shotgun Sequencing - 1]
# Trivedi, B. (2000). ''Sequencing the Genome''. Retrieved September 4, 2009, from [http://www.genomenewsnetwork.org/articles/06_00/sequence_primer.shtml Shotgun Sequencing - 2]
# Mage, R. (2008). Rabbit genome sequencing update: genes of immunological interest found in the 2x genome assemblies, ENCODE, and the 7x trace archive. ''Journal of FASEB'' 22(Retrieved September 5, 2009, from [http://www.fasebj.org/cgi/content/meeting_abstract/22/2_MeetingAbstracts/559/ Rabbit Genome & its Immunological Interest]
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# Korstanje, R. et al. (1999) Complete homology maps of the rabbit (Oryctolagus cuniculus) and human by reciprocal chromosome painting. ''Cytogenetics and cell genetics'' ''86''(3-4), 317-322. Retrieved September 6, 2009, from [http://cat.inist.fr/?aModele=afficheN&cpsidt=1189693/ Complete homology maps of the rabbit Article] "PMID 10575232"
# Brunner, R., Knopp, A., Rudolph, W. (n.d). Rabbit chromosome analysis by image processing. ''Journal of Applied Rabbit Research''.
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# Hofsaess, F., and Meacham, T. ( 1995) Chromosome abnormalities of early rabbit embryos. ''Journal of Experimental Zoology''. ''177'' (1): 9-11 [http://www3.interscience.wiley.com/journal/110490865/abstract/ Chromosome abnormalities]
# Martin-Deleon, P., Shaver, E., and Gammal, E. (1973) Chromosome abnormalities in rabbit blastocysts resulting from spermatozoa aged in the male tract. ''Fertility and Sterility''. ''24''(3):212-219.
# Patil, M. et al (2004) Chromosome analysis of domestic rabbit. ''The Journal of Bombay Veterinary College''. ''12'' (1 and 2)
#Biggers J.D (1991) Walter Heape FRS: a pioneer in reproductive biology. centenary of his embryo transfer experments.''Journals of reproduction and fertility''. ''93''(1)
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# National Institute of Neurological Disorders and Stroke (2008, February). Hydrocephalus Fact Sheet. Retrieved from [http://www.ninds.nih.gov/disorders/hydrocephalus/detail_hydrocephalus.htm]
# Lewin, R (1999). Is Your Brain Really Necessary?. 24) Developmental Medicine & Child Neurology, 41. Retrieved from [http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=176431]
# Bigio, M.R, & Bruni J.E (1991). Silicone oil-induced hydrocephalus in the rabbit . Child's Nervous System, 7(2), Retrieved from [http://www.springerlink.com/content/b011477724837152/]
# Geelen, J.A (1974). A case of hydrocephalus and meningoencephalocele in a rabbit, caused by aqueductal malformation. Laboratory Animals, 8(2), Retrieved from [http://la.rsmjournals.com/cgi/content/abstract/8/2/167]
# LAMMINGX, G.E (1954). 27) Hydrocephalus in Young Rabbits Associated with Maternal Vitamin A Deficiency. British Journal of Nutrition, 8(2), Retrieved from [http://journals.cambridge.org/download.php?file=%2FBJN%2FBJN8_04%2FS0007114554000554a.pdf&code=10bb1dbc4a9e57a091f4e05f6aebbcf2]
# Carney, A (2008, February ). Spina bifida. Retrieved from [http://www.spinabifida.asn.au/]
# Better Health Channel (2008, October ). Spina bifida explained . Retrieved from [http://www.betterhealth.vic.gov.au/bhcv2/bhcarticles.nsf/pages/Spina_bifida_explained]
# Peeters, M.C, Viebahn, C, & Hekking, J.W (1998). Neurulation in the rabbit embryo . Anatomy and Embryology, 197(3), Retrieved from [http://www.springerlink.com/content/1efyteewgetjlwyg/]
# George, T.M, & Fuh E (2003). Review of Animal Models of Surgically Induced Spinal Neural Tube Defects: Implications for fetal surgery. Pediatric Neurosurgery , 39(2), Retrieved from [http://content.karger.com/produktedb/produkte.asp?typ=fulltext&file=PNE2003039002081]
# Pedreira, D.A, & Valente P.R (2002). A Different Technique to Create a 'Myelomeningocele-Like' Defect in the Fetal Rabbit. Fetal diagnosis and therapy, 17(6), Retrieved from [http://content.karger.com/ProdukteDB/produkte.asp?Doi=65388]
# Patten, B.M (1953). Embryological stages in the establishing of myeloschisis with spina bifida. The American journal of anatomy, 93(3), Retrieved from [http://deepblue.lib.umich.edu/handle/2027.42/49611]
# Pedreira, D.A, & Valente P.R (2003). Successful Fetal Surgery for the Repair of a 'Myelomeningocele-Like' Defect Created in the Fetal Rabbit. Fetal Diagnosis and Therapy, 18. Retrieved from [http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowPDF&ProduktNr=224239&Ausgabe=229041&ArtikelNr=69378]
# Lecklitner, M.L, & Douglas K.P (1986). Osteoscintigraphy and brachydactylia of the hand . European Journal of Nuclear Medicine and Molecular Imaging, 12(9), Retrieved from [http://www.springerlink.com/content/t82l77282x579102/]
# Greene, H.S, & Saxton J.A (1938). HEREDITARY BRACHYDACTYLIA AND ALLIED. ABNORMALITIES IN THE RABBIT. THE JOURNAL OF EXPERIMENTAL MEDICINE , 69. Retrieved from [http://jem.rupress.org/cgi/reprint/69/2/301.pdf]
# P. Ianakiev, M. van Baren, M. Daly, S. Toledo, M. Cavalcanti, J. Neto, E. Silveira, A. Freire-Maia, P. Heutink, M. Kilpatrick. Acheiropodia Is Caused by a Genomic Deletion in C7orf2, the Human Orthologue of the Lmbr1 Gene. The American Journal of Human Genetics, 68. Retrieved from [http://linkinghub.elsevier.com/retrieve/pii/S0002929707624707]
# Walbaum, R, Hazard, C, & Cordier, R (1976). Brachydactylia with symphalangism, probably autosomal recessive . Human Genetics, 33(2), Retrieved from [http://www.springerlink.com/content/m630p6880661486n]
# Campbell, N.A, & Reece, J.B (2002). Biology 6th Edition. USA: Benjamin Cummings.
# Solomon, E.P, Berg, L.R, & Martin, D.W (2002). Biology 6th Edition. USA: Thompson Learning.
# Glanville, A.R (2008). Scientifica. NSW, Australia: Millennium House.
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# Jones, B.W, & Marc R.E (2008). Computational Molecular Phenotyping and Excitation Mapping in the P347L. Retinal Degeneration , (2986), Retrieved from [http://prometheus.med.utah.edu/]
# Kondo, M, Sakai, T, & Ueno, S (2009). Generation of a Transgenic Rabbit Model of Retinal Degeneration. Investigative Ophthalmology and Visual Science, 50. Retrieved from [http://www.iovs.org/cgi]
# Punzo, C, Chen, B, & Roesch, K (2009). PHOTORECEPTOR DEATH IN MOUSE MODELS OF RETINITIS PIGMENTOSA. Retrieved from [http://genepath.med.harvard.edu]
# Zimmer, M (2008). Alba. Retrieved from [http://www.conncoll.edu/ccacad/zimmer/GFP-ww/cooluses8.html]
# Scott, C (2006, May 1). Chimeras in the crosshairs. Nature Biotechnology , 24, Retrieved from [http://www.nature.com/nbt/journal/v24/n5/abs/nbt0506-487.html]
# Mott, M (2005, January 25). Animal-Human Hybrids Spark Controversy. National Geographic News, Retrieved from [http://theyfly.com/PDF/Nat.%20Geo.%20Animal-Human%20Hybrids.pdf]
# Li, S, & Chen X (2006). Rabbits generated from fibroblasts through nuclear transfer . Society for Reproduction and Fertility, 131. Retrieved from [http://www.reproduction-online.org/cgi/reprint/131/6/1085]
# Minger, S (2007). Interspecies SCNT derived human embryos. Regenerative Medicine, 2(2), Retrieved from [http://www.futuremedicine.com]
# Koga, H, Shimaya, M, & Muneta, T (2008). Local adherent technique for transplanting mesenchymal stem cells as a potential treatment of cartilage defect. Arthritis Research & Therapy, 10(4), Retrieved from [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2575632]
# Wang, J, Li, C, & Sun, Y (2005). Human bone marrow-derived mesenchymal stem cells transplanted into damaged rabbit heart to improve heart function. Journal of Zhejiang University Science, 6(4), Retrieved from [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1389731]
# Chen, Y, Liu, A, & Mao, W (2003). Embryonic stem cells generated by nuclear transfer of human somatic nuclei into rabbit oocytes. Cell Research , 13(4), Retrieved from [http://www.nature.com]
# Bethesda (2009, September 23). Stem Cell Information. Retrieved from [http://stemcells.nih.gov]
# Cibelli, J. B. (2002). Principles of cloning Amsterdam. Academic Press
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# Warner, S. (2003). Inositol transport in preimplantation rabbit embryos: Effects of embryo stage, sodium, osmolality and metabolic inhibitors Reproduction, 125(4), 479-493.
# Derelanko, M. J. (2008). The toxicologist's pocket handbook, second edition Informa HealthCare
# Beaudoin, S., Barbet, P., & Bargy, F. (2003). Developmental stages in the rabbit embryo: Guidelines to choose an appropriate experimental model Fetal Diagnosis and Therapy, 18(6), 422-427.

==Glossary==

Anesthetic - A drug that causes temporary loss of bodily sensations

Aplasia - The absence or defective development of a tissue or organ

Blastocyst - A stage of embryo development that occurs about five days after fertilisation when the embryo contains quite a few cells

Caudal - Situated towards the inferior or posterior end of the body

Cephalic - Relating to the head

Cerebral Aqueduct - A canal filled with cerebrospinal fluid within the midbrain

Cerebral Cortex - The layer of unmyelinated neurons (the grey matter) forming the cortex of the cerebrum of the brain

Cerebro Spinal Fluid (CSF) - A watery fluid which flows in the cavities within the brain and around the surface of the brain and spinal cord

Chromosome - Microscopic carriers of genetic material, composed of deoxyribonucleic acid (DNA) and proteins and appearing as rods under a microscope

Cisterna Magna - is one of three principal openings in the subarachnoid space between the arachnoid and pia mater layers of the meninges surrounding the brain

Diploid - A full set of genetic material, consisting of paired chromosomes one chromosome from each parental set

Dorsal - Position towards the back

Fontanel - Membranous gap between the bones of the cranium in an infant or fetus

Genome - All genetic information, the entire genetic complement and all of the hereditary material possessed by an organism. Made up of both chromosomal genome (inside the nucleus of the cell in the familiar form of chromosomes) and mitochondrial genome (outside the nucleus in the cytoplasm of the cell, usually in the form of one round chromosome (the mitochondrial chromosome))

Genotype - The genetic makeup of an organism

Glucocorticoids - A class of steroid hormones that bind to the glucocorticoid receptor (GR), which is present in almost every vertebrate

Haploid - A single set of chromosomes (half the full set of genetic material)

Laparotomy- Surgical incision into the abdominal wall; often done to examine abdominal organs

Ligases - Group of enzymes that catalyze the binding of two molecules

Oocyte - A female gametocyte that develops into an ovum after two meiotic divisions

Phenotype - The observable traits or characteristics of an organism, for example hair color, weight, or the presence or absence of a disease.

Pronuclear - Haploid nucleus before fusion of nuclei in fertilisation

Restriction Endonucleases - Enzymes that recognize and cleave specific DNA sequences, generating either blunt or single-stranded (sticky) ends

Retina - The thin layer of cells at the back of the eyeball where light is converted into neural signals sent to the brain

Rostral - Situated toward the oral and nasal region

Somite - Blocks of mesoderm on either side of the notochord and neural tube during development of the vertebrate embryo. Develop into muscles and vertebrae

Stenosis - Abnormal narrowing of a bodily canal or passageway

Weaning - Young become accustom to nourishment other than suckling

==Links to Research Laboratories and Researchers==

1) Transgenic lab: [http://www.dnavision.be/index.php]

Involved in development of transgenic organisms, DNA construction and phenotype analysis.

2) World Rabbit Science Association: (WRSA) [http://world-rabbit-science.com]

International Association where researchers exchange knowledge and encourage teaching, scientific research, practical experimentation, the collection and publication of statistics and documents relating to the rabbit. Even have their own journal called “World Rabbit Science”

Website provides contact with researchers, professors and veterinarians working with rabbits.

Example: Dr. Myriam Kaplan-Pasternak, Doctorate Veterinary Medicine, University of California, myriamsemail@gmail.com

3) American Veterinary Medical Association [http://www.avma.org]

The American Veterinary Medical Association (AVMA), established in 1863, is a not-for-profit association representing more than 78,000 veterinarians working in private and corporate practice, government, industry, academia, and uniformed services. Excellent website into animal research and has a range of veterinary journals.

{{Template:Projects09}}
[[Category:Rabbit]]
[[File:Example.jpg]]

2009 Group Project 1

2009-10-14T11:54:35Z

Z3185685: /* Timeline of Embryo Development */

[[File:Rabbits.png|right|400 px]]

== '''THE RABBIT (ORYCTOLAGUS CUNICULUS)''' ==

==Introduction==

[[File:Isidro_Martinez.jpg‎|left|175 px]]

Several characteristics of the rabbit make it an excellent model for study. Many studies have resulted in the development and improvement of various micro-manipulation techniques such as the production of transgenic rabbits. The rabbit is an appropriate animal model as the results from many experiments are significant to that of other mammals, including humans. (55)

A rabbits potential for reproduction is high, breeding from the early stages of 3 to 4 months of age. A mature female rabbit can be pregnant from 6 to 8 months in a year, producing up to 30 to 40 young in this time. (56)

==History of Model Use==

'''WHY are we using rabbits?'''

ADVANTAGES
*Provides repeatability of animal model studies
*Large enough for single samples
*Many stocks/strains as animal models
*Easily managed
*Quality of immunologic products
*Ease of reproductive control

DISADVANTAGES
*Most colonies are a storehouse of diseases
*Extremely variable to responses to general anesthetics

'''Brief timeline of rabbit embryo model use'''

*1672- de Graaf found the Graffian follicle.
*1890- Walter Heape succeeded first mammalian embryo transfer
*1906- FT Lewis discovered the development of the lymphatic system in rabbit embryos.
*1941- Dr. Pincus succeeded in keeping rabbit embryos developing in the test
*1968- Edwards and Gardner successfully performed the first known embryo biopsy on rabbit embryos

=== Regnier de Graaf (1641–1673) ===
[[image:Ovary_Graaf.jpg|thumb|250px|left|drawing of ovary]]
[[File:Regnier de Graaf.jpg|right]]

'''Discovery of the Graafian Follicles'''

In 1672 de Graaf published ''The Generative Organs of Women'', which was primarily a study of development in the rabbit. When de Graaf discovered large, round welling on the ovaries of rabbits, he assumed they were mammalian eggs. De Graaf also described the corpus luteum.

He summarised the previous works from anatomists, but unable to experience the amazing benefits made by microscopy.
But Antonie van Leeuwenhoek (A microbiologist, 1632 - 1723) argued that the structures now known as Graafian follicles could not be eggs. Haller suggested that the egg might be formed by the coagulation of the fluid within the Graafian follicle. De Graaf noted that the “egg” did not contain a tiny embryo, but he thought it did contain the “germ” of the future organism. (3)

=== Walter Heape (1855-1928) ===
'''First case of embryo transfer experiments'''

On 27 April 1890, Walter Heape (a professor and physician at the University of Cambridge, England) transferred rabbit embryos from one mother to another. (7) One rabbit mother became pregnant and delivered young from the transferred embryos. This was the first mammalian embryo transfer experiment to be successfully completed. His embryo transfer work in perspective as it relates to other contributions of this pioneer in reproductive biology.(7)

In 1891, Walter Heape had been conducting research on reproduction in numerous animal species. Working with two species of rabbits, he flushed embryos from the rabbit fallopian tubes of one breed (Angora) and placed them into the uterus of a recently mated Belgian hare. In the resulting litter, there were 4 Belgians and 2 Angoras. Heape proved that it was possible to take preimplantation embryos and transfer them to a gestational carrier without affecting their development.(7)

===Dr. Gregory Goodwin Pincus (1903-1967) ===

'''Contraceptive pill'''

Dr. Pincus began studying hormonal biology and steroidal hormones early in his career. His first breakthrough came when he was able to produce in vitro fertilization in rabbits (by using chemicals) in 1934. Throughout their hormonal contraceptive research Pincus, along with reproductive physiologist Min Chueh Chang, found out progesterone would act as an inhibitor to ovulation. They co-invented the combined oral contraceptive pill.[2][6]

===Genetic Diagnosis===
In 1968, Robert Edwards and David Gardner reported the successful sexing of rabbit blastocysts, setting the first steps towards PGD (Preimplantation Genetic Diagnosis). It was not until the 1980s that human IVF was fully developed, which coincided with the breakthrough of the highly sensitive polymerase chain reaction (PCR) technology. Handyside and collaborators' first successful attempts at testing were in October 1989 with the first births in 1990 though the preliminary experiments had been published some years earlier. In these first cases, PCR was used for sex determination for patients carrying X-linked diseases.(12)

==Timeline of Embryo Development==

The following is a timeline, adapted from Cibelli (2002), of the main events of preimplantation development in rabbits. The time is measured in hours post-mating and shows the embryo stage (cell number) in each time scale.

[[File:Morula1.JPG|right|200 px|thumb|A day 2 early morula]]

'''12-14 hours:''' Oocyte; Fertilization

'''18-20 hours:''' Zygote; Pronuclear formation

'''24-26 hours:''' Two cell

'''30-32 hours:''' Four cell

'''38-40 hours:''' Eight cell; Maternal-zygotic transition

'''46-48 hours:''' Sixteen cell

'''54-56 hours:''' Morula (32 cell); Compaction and transport to uterus

'''64-66 hours:''' Compact morula (64 cell); Morula-blastocyst transition

'''76-78 hours:''' Early blastocyst (128 cell)

'''84-86 hours:''' Expanded blastocyst (256 cell); Blastocoels expansion

'''94-96 hours:''' Hatched blastocyst (512 cell); Hatching

The following shows a diagrammatic representation of the relative sizes of rabbit embryos. The sizes do not include the embryonic coverings such as the zona pellucida and mucin coat. This diagram has been adapted from Warner (2003).

[[File:Sizes.JPG]]

The following timelines show a comparison of the developmental stages between human and rabbit embryos. They have been adapted from Derelanko (2008). "The similarities of this developmental pattern in humans and rabbits, suggests that the same growth increment is required to achieve the same stage. The main difference observed between human rabbit gestational duration is due to the fetal growth phase. The reason for this may be due to birth weight, lifetime and the neural complexity of the species." (59)

[[File:Timeline_rabbit.JPG]]

The following timelines have been adapted from a study carried out by Beaudoin et al. on the development of rabbit embryos.

==='''Body Form'''===

'''8.5 days''': Embryo thickens. First somites appear. Rostral neuropore closes. Caudal neuropore remains open

'''9.5 days''': Dorsal curvature begins. Cardiac mass bulges under cephalic pole.

'''10.5 - 13.5 days''': Dorsal curvature increases. Body thickens. Softening of the cephalic domination straightens the embryo.

'''17.5 days''': Neck becomes visible.

==='''Limb Development'''===

''' 9.5 days''': Rostral limb bud appears

'''10.5 days''': Caudal limb bud appears

'''12.5 days''': Hand plate becomes present. Limbs become disposed.

'''13.5 days''': Foot plate and finger rays become visible.

'''14.5 days''': Rostral and caudal limbs become parallel.

'''15.5 days''': Elbow appears.

'''16.5 days''': Fingers start to elongate.

'''17.5 days''': Knee becomes visible

'''19.5 days''': Hands and feet merge on the midline. Three segments of limbs become distinguished.

==='''Abdominal Wall Development'''===

'''9.5 days''': Abdominal wall is limited to the embryonic pedicle under the cardiac mass.

'''13.5 days''': First intestinal loops appear in the umbilical cord.

'''14.5 days – 17.5''': Rapid intestinal development in the cord.

'''15.5 days''': Abdominal vesicles can be observed.

'''16.5 days''': Cecal bud becomes present outside the abdomen

'''18.5 days''': Bowel returns to the abdominal cavity and umbilical ring closes.

==='''Cephalic Development'''===

'''9.5 days''': One cerebral vesicle can be seen. Pharyngeal arches as optic vesicle are present.

'''10.5 days''': Three arches are distinguished in the cephalic pole.

'''11.5 days''': Three cerebral vesicles present. Optic plate is distinguished.

'''12.5 days''': Face develops nasal, maxillar and mandibular buds. Lens vesicle is closed. Five cerebral vesicles exist.

'''14.5 days''': The ear becomes refined. Face can be distinguished from the brow.

'''18.5 days''': Eyelid appears, covering the eyes.

==Staging==

The following stages have been adapted from Beaudoin et al. (2003). Table 1 represents at each age its corresponding stage defined by the Carnegie classification

{| class="wikitable" style="text-align:center; width: 800px; height:1000px" border="1"
|+'''Table 1. Rabbit developmental stages using Carnegie classification'''

|- style="height:50px"
! '''Stage''' !! '''Days''' !! '''Event''' !! '''Image'''
|- style="width:200px"
! width="50" | 10
| width="50" | 8.5 || First somites appear, rostral neuropore closes
|- style="height:75px"
! 12
| 9.5 || Rostral limb bud, embryonic pedicle, caudal neuropore closes, one cerebral vesicle, pharyngeal arches, completion of optic vesicle
| [[file: 9.5new.JPG|100px]]
|- style="height:75px"
! 13
| 10.5 || Dosral C-shaped curvature, caudal limb bud, prominent cardiac swelling, four pharyngeal arches
| [[file: 10.5new.JPG|100px]]
|- style="height:75px"
! 14
| 11.5 || Three cerebral vesicles, optic plate, mesonephric ridge
|- style="height:75px"
! 15
| 12.5 || Hand plate, wheel ray limbs, lens vesicle closes, five cerebral vesicles, facial buds, vertebrae
| [[file: 12.5new.JPG|100px]]
|- style="height:75px"
! 16
| 13.5 || Foot plate, finger rays, prominent liver, intestinal loops, auricular hillocks
| [[file: 13.5new.JPG|100px]]
|- style="height:100px"
! 19
| 14.5 || Cuboidal body, trunk straightens, parallel limbs, toe rays, modeled face, visible auricle
| [[file: 14.5new.JPG|100px]]
|- style="height:75px"
! 20
| 15.5 || Elbow, fingers elongate, notches between toe rays
| [[file: 15.5new.JPG|100px]]
|- style="height:75px"
! 21-22
| 16.5 || Toes free, cecal bud in intestinal hernia
| [[file: 16.5new.JPG|100px]]
|- style="height:75px"
! 22-23
| 17.5 || Knee, neck, eyelids
| [[file: 17.5new.JPG|100px]]
|- style="height:75px"
! 23
| 18.5 || Hands and feet join at the midline, closure of abdominal wall, eyelids cover eyes
| [[file: 18.5new.JPG|100px]]
|-
| colspan="4" align="center"| Following this stage fetal appearance is completed, organogenesis is achieved
|}

==Genetics==

===Sequencing===
The National Human Genome Research Institute selected the European rabbit (Oryctolagus cuniculus) for whole genome sequencing to enhance their understanding of the human genome and use it experimentally for an animal model for human disease. (8)

The rabbit has been sequenced twice by The Broad Institute as part of the mammalian genome project. It is now currently undergoing 7 more sequencing projects. Its sequencing is made by the Whole Genome Shotgun (WGS) and assembly method. (9) This is when genomic DNA is sheared into small pieces of approximately 2000 base pairs which are then cloned into plasmids and sequenced on both strands. Once the contig fragments are read, realigned and reassembled by computer algorithms, it will give the overall sequence. (10) (11) The image below shows diagramatically how the two types of sequencing are different. The same techniques are used for sequencing the human genome (in 2003). [A contig is a set of overlapping DNA segments, derived from a single source of genetic material, from which the complete sequence may be deduced.

The whole genome shotgun (WGS) has serious gaps, yet the information has already proven useful for immunological as well as in silico studies. Deeper 7x coverage started in September 2007. The NCBI Rabbit Genome Resources site has links to searches for genes in the assemblies of the 2x WGS sequence at Ensembl and UCSC.(12) [http://www.broadinstitute.org/models/europeanrabbit/ Rabbit Genome Project]

[[File:WGS_sequencing.gif‎|center|800 px]]

===Genome===
The Rabbit genome was published by two groups (9)
# Lindblad-Toh,K., Chang,J.L., Gnerre,S., Clamp,M. and Lander,E.S. published their admission of 84024 bases on May 5th 2005 to The Broad Institute (USA) by shotgun sequencing
# Di Palma,F., Heiman,D., Young,S., Gnerre,S., Johnson,J., Lander,E.S. and Lindblad-Toh,K. published their admission of 84024 bases on August 3rd 2009 to The Broad Institute (USA) by shotgun sequencing.
The rabbit's genome is sequenced and on display in the Nucleotide Data Bank. It is too long to produce here. A link to the data bank is provided: [http://www.ncbi.nlm.nih.gov/nuccore/256946799/ Rabbit Genome from the Nucleotide Data Bank]

[[File:8cellembryo.jpg|thumb|Individual mitochondria (arrowheads) of an 8cell Rabbit embryo]]

The rabbit genome was sequenced in 2005 by Ensembl and managed to produce: (13)
* 2,076,044,328 supercontigs (ordered Contigs with gaps)
* 495 Known protein-coding genes
* 11,357 Projected protein-coding genes
* 2,343 RNA genes
* 212,581 Gene exons
* 20,311 Gene transcripts

For further research the taxonomy ID number for the Rabbit is: 9986 [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=9986&lvl=3&lin=f&keep=1&srchmode=1&unlock/ Taxonomy Data]

===Mitochondrial Genome===
The mitochondiral genome (mtDNA) of the rabbit was sequenced on November 14th 2006 with 17245 base pairs/nucleotides in circular form. Apparently the "length is not absolute due to the presence of different numbers of repeated motifs in the control region".
PMID 9653643

The image to the right shows the mitochondria during cell division and multiplication in embryo development.

=== Chromosomes ===
Over the years there have been various data suggesting the diploid chromosomal number for the rabbit may range from 22-42. However through recent research and an abundance of trials suggest that the rabbit does indeed have 22 different chromosome pairs existing in each cell of the rabbit. (16)(17) The sex chromosomes of the rabbit are of X-Y type convincingly (17). In a study in Bombay it confirmed that a rabbit has 2n = 44 chromosomes. There were 21 pairs of autosomes, out of which 1 to 6 were metacentric, 7 to 11 submetacentric, 12 to 17 subtelocentric and 18 to 21 acrocentric, plus the sex chromosomes. The image to the left shows a female rabbit with no chromosomal abnormalities. (19)

'''Comparison to human chromosome:'''

Rabbit chromosomes 12, 19 and X were found to be completely homologous to human chromosomes 6, 17 and X, respectively. All other human chromosomes were homologous to two or sometimes three rabbit chromosomes. (14) Chromosome 12 was shorter than chromosomes 13 and 14. (15) The image below illustrates the human chromosome (2n = 46).

[[File:Drawn chromosome.jpg|left|400 px]]

[[File:Karyotypehuman.gif|right|500 px]]

'''Abnormalities'''

These are generally more apparent during early embryo development in blastocysts from delayed fertilization. Some examples of abnormal development include cases of: (18)
* hypoploidy; 1 chromosome missing from a pair (2n = 43),
* double hypoploidy; 2 chromosomes missing from 2 different pairs (2n = 42),
* mosaicism (different chromosomal makeup in some cells).

Another study also found these abnormalities as well as: (19)
* autosomal trisomy (3 autosomes per pair),
* triploidy (extra set of chromsomes),
* mixoploidy (unequal number of chromosome sets in adjacent cells), and
* short arm deletion (deletion of parts of chromosomes).

A specific abnormality occurring in rabbits is the x-linked tremor. There is a mutation in exon 2 of the prteolipid-protein (PLP 1) gene, corresponding to the end of the first potential transmembrane domain of the protein. This disorder affects myelination of the central nervous system. OMIA ID:12 [http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=full_report&list_uids=100009169&log$=omiamaingene| Gene:100009169]

==Abnormal Development==

Abnormal embryological development is a vast field of study that has been the subject of recent research papers. Our investigation of abnormal development in rabbit embryology will focus on abnormalities commonly found in both rabbit and human embryos. We will explore the nature of these abnormalities in both humans and rabbits.

[[File:Normal v Abnormal.jpg|right|300 px|thumb|Brain MRI of patient with Hydrocephalus (left) compared to a normal brain (right). An obvious increase in ventricular size and a significant decrease in brain size is present.]]
[[File:Ventricle_Expansion.jpg|right|300 px|thumb|CSF accumulation in ventricles of brain increasing intracranial pressure.The pressure from the expanding ventricles force the brain and skull to grow outwards abnormally.]]

'''Hydrocephalus'''

Annually, one in every 1000 children born in Australia have hydrocephalus. Hydrocephalus occurs when excessive cerebrospinal fluid (CSF) accumulates in the brain and can result in severe disability and even death because the disorder can result in complete or near complete destruction of the cerebral cortex (22).

Children born with hydrocephalus typically exhibit abnormally large head circumference and bulging cranial fontanels as a result of increased intracranial pressure on the brain from the accumulating CSF (22,23). As CSF accumulates in the ventricles and CSF compartments of the brain, it expands forcing the brain to grow outward. The outward growing brain places pressure on the skull which in turn also grows outwards giving rise to an abnormally large head circumference and bulging cranial fontanels (22,24). It is generally acknowledged that children with hydrocephalus have mental retardation, often to the degree of being “vegetative” (24).

The serious consequences of this disease mean that much research is necessary to unearth methods of prevention and effective treatment. One of the modes of studying hydrocephalus is to use the rabbit experimental model where hydrocephalus can be induced in rabbit embryo’s. The injection of silicone oil into the cisterna magna of the brain is one way of inducing hydrocephalus in the rabbit embryo. The silicone oil obstructs the normal flow of CSF resulting in CSF accumulation in the brain leading to hydrocephalus (25). Another method of inducing hydrocephalus in rabbit embryo’s is by intentional vitamin A deprivation of pregnant dams. The vitamin A deficiency results in raised intracranial CSF pressure and aqueduct stenosis causing poor circulation of CSF leading to hydrocephalus (26,27). Although the exact function of vitamin A on brain development and CSF regulation is not fully understood, it is clear that Vitamin A has an important role in brain development and its normal functioning (27).
[[File:Rabbithhdrocephalus.jpg|center|300 px|thumb|Young rabbit with hydrocephalus caused by Vitamin A deficiency. Note the abnormally shaped cranium inflamed in appearance.]]

[[File:SpinabifidaMeningocele1.jpg|right|300 px|thumb|Spina Bifida Meningocele has characteristic damage to the meninges of the spinal cord which are pushed out through an opening in the vertebrae as a cyst filled with CSF.]]
[[File:SpinaBifidaMyelomeningocele.jpg|right|300 px|thumb|Spina Bifida Myelomeningocele is the most severe form of spinabifida where the damaged spinal cord protrudes out with damaged meninges as a cyst filled with CSF.]]
[[File:SpinaBifidaOcculta1.jpg|right|300 px|thumb|Spina Bifida Occulta is the least severe as the spinal cord and meninges are undamaged.]]

'''Spina Bifida'''

In Australia, the risk of spina bifida is 1 in every 500 pregnancies. Spina bifida is a type of neural tube defect where vertebrae (which normally cover and protect the spinal cord) are not completely formed but are divided resulting in the defective spinal cord and its coverings to protrude through the opening (28,29).

There are three main types of Spina Bifida differentiated by their characteristic features:

1)Spina Bifida Meningocele characterized by normal spinal cord, divided outer vertebrae and meninges surrounding the spinal cord protruding from the divided vertebrae as a cyst (1,28).

2)Spina Bifida Myelomeningocele characterized by split outer vertebrae with spinal cord and its meninges protruding from the divided vertebrae as a cyst. Commonly found at lumbar vertebral level (1,28,29).

3)Spina Bifida Occulta characterized unfused vertebral arches and exposed vertebral canal. Spinal cord and its meninges still located in vertebral canal (1,28).

All forms of spina bifida are potentially fatal and in those where the spinal cord is damaged severe consequence arise including and paralysis and loss of sensation at and below the level of damage spinal cord damage (29,33). There is a lot of Spina bifida research using rabbit models to test the effective methods of correcting spina bifida. The occurrence of natural spina bifida in rabbits is rare and for experimental purposes it can be surgically created in rabbit fetuses during gestation (31,32). The process involves aesthetical sedation of the maternal rabbit at day 22 of gestation; a midline laparotomy performed and the desired type of spina bifida lesion created on the exposed fetus using forceps. Different methods for correcting spina bifida can then be tested and its effectiveness analysed (30,33,34).
[[File:Rabbitspinabifida1.jpg|center|350 px|thumb|Rabbit newborn with Spina Bifida. Note the unfused, divided vertebrae and exposed spinal cord.]]

'''Brachydactylia & Acheiropodia'''

[[File:Malformation1.jpg|right|150 px|thumb|Acheiropodia in rabbit characterized by amputations of the limbs and extremities.]]

[[File:Rabbitmalformation3.jpg|left|150 px|thumb|X-Ray study of rabbit limbs with malformed phalanges due to Brachydactylia.]]

Brachydactylia and Acheiropodia are genetic disorders characterized by skeletal malformation of the hands and feet (36,36). In Brachydactylia, the malformations commonly involve abnormal shortening of fingers and toes due to poorly formed or absent bones (35). Acheiropodia is characterized by more severe skeletal malformations including bilateral amputations of the distal upper and lower extremities as well as aplasia of the hands and feet. Although it is not fatal, the individual endures a very difficult life without hands and feet (37).

The inheritance mechanism of this diseases can has been studied through experiment using rabbits. Rabbits with abnormal genes coding for Brachydactylia and Acheiropodia are selected and bred to produce offspring with the disease (36). Brachydactylia and Acheiropodia are autosomal recessive disorders which means that two copies of an abnormal gene must be present in the affected individual in order for the disease to develop. Thus, each parent passes an abnormal gene to the offspring (35,36). The process of the malformation progresses from genotype to phenotype; small deletions on the chromosomes produce abnormal genes, the abnormal genes are then passed down to the offspring, the offspring that inherits two of the abnormal genes is unable to code for the correct proteins and as a result, there is failure in normal development of limb extremities in the embryo phenotype (37,38).

==Current Embryology Research==

There is currently great excitement in research involving rabbits in the fields of transgenesis, cloning and stem cells. We shall explore research in these areas by discovering some of the techniques used and how they have been applied to the rabbit model.

[[File:Trans1.jpg|right|170 px]]
[[File:Trans2.jpg|right|170 px]]
[[File:Trans3.jpg|right|170 px]]
[[File:Trans4.jpg|right|170 px]]
[[File:Trans5.jpg|right|170 px]]

'''Transgenic rabbit'''

A transgenic organism is one whose genome also contains genes from another species (39). The aim of creating a transgenic organism is to obtain a favorable characteristic in the organism’s phenotype (41). This desired characteristic of phenotype is obtained by altering the organism’s normal genotype to include the gene from another species with the desired characteristic (39,40).

The production of a transgenic organism involves several steps summarized below:

1) The chromosome and the desired gene on it are identified in an organism (39).

2) The gene is isolated from its DNA strand. This involves “cutting” it out of its DNA strand using enzymes called restriction endonucleases. The restriction endonucleases cut DNA at specific site so the desired gene can be removed from the DNA strand. The cut ends are known as “sticky ends” (39,40).

3) Separate DNA sequences for regulation sometimes have to be added to ensure the gene will work (40).

4) The gene is then inserted with a promoter sequence into the fertilized egg cell of a new organism producing recombinant DNA (39,44). To do this, firstly the new organism’s cell DNA must first be cut and the desired gene incorporated into it. The same enzymes are used to cut the new organism’s cell DNA because the DNA stands from the two different organisms will form matching sticky ends that will be attracted to and connect with each other in a process is called “annealing” (39,40,44).

5) DNA ligases are sealing enzymes found in all living organisms that help make and repair DNA (39,40). The DNA ligases are added to the annealed DNA fragments to help strengthen the bonds of the new recombinant DNA. The recombinant DNA is now transferred into the new organism’s fertilized egg by microinjection (44).

6) As the embryo develops and the recombinant genetic code read, new proteins are synthesized which code for the new desired phenotype characteristic in the transgenic organism (39,40).

Transgenic rabbits can be created in the laboratory by gene microinjection into the fertilized rabbit oocyte (44). In April 2000, a transgenic rabbit named Alba was born containing a gene from a Pacific Northwest jellyfish. The gene which was injected into a fertilized albino rabbit oocyte allows the rabbit to synthesize the green fluorescent protein (GFP) that is characteristic of the Pacific Northwest jellyfish. When illuminated correctly, Alba glows a bright green (43,46).

Transgenic rabbits have important research purposes. Transgenic rabbits can be created to model retinal degeneration (44). Retinal degeneration is a common problem with aging and diseases such as diabetes, and frequently leads to complete blindness (42). A genetic retinal degeneration disease called retinitis pigmentosa (RP) is created in these rabbits by introducing the “Pro347Leu” mutation of the rhodopsin gene into fertilized rabbit eggs (43,44). As the rabbit grows, it develops the disease which becomes progressively worse (45).
The use of these transgenic rabbits ultimately leads to better understanding of the disease and more effective treatments (42). [[File:Transgenic rabbit.jpg|center|250 px|thumb|"Alba" A trangenic rabbit with a gene from a Pacific Northwest jellyfish that allows it to synthesize the green fluorescent protein (GFP) of the jellyfish.]]

[[File:Crabbit 1.jpg|right|170 px]]
[[File:Rabbit2.jpg|right|170 px]]
[[File:Rabbit3.jpg|right|170 px]]
[[File:Crabbit 4.jpg|right|170 px]]

'''Cloning'''

Cloning is a method of producing genetically identical organisms. The principle of cloning relies on “tricking” an egg cell to begin rapidly dividing into an embryo (39). In the normal fertilization process, two haploid sex cells unite to form a diploid zygote which begins rapidly dividing into an embryo (40). By replacing the haploid egg cell nucleus with a diploid somatic cell nucleus, the egg cell is tricked into thinking it is fertilized and hence begins rapidly dividing to form an embryo (39,40,41).

The process of cloning involves several steps summarized as the following using a rabbit example:

1) A somatic cell is obtained from a rabbit and the nucleus removed (39).

2) An egg cell is obtained from a donor rabbit and the nucleus of the egg cell removed using an enucleation needle. The cell is now called an enucleated egg cell (egg cell without a nucleus) (39,41).

3) The nucleus of the somatic cell is inserted into the enucleated egg cell (41).

4) The cell is now stimulated to divide by applying pulses of electric current (39).

5) The rapidly dividing cell develops in culture for a few days forming the early embryo (40,41).

6) The embryo is then implanted into the uterus of another rabbit similar to the egg cell donor. This rabbit is called the surrogate mother (40,41).

7) The embryo develops and the surrogate mother gives birth to a rabbit fetus with near identical genotype of the somatic cell donor (the small genomic difference is caused by the fetus obtaining mitochondrial DNA from the egg cell donor) (39,41).

The cloning of rabbits has been achieved by inserting the diploid nucleus of a rabbit fibroblast (the principal cells in connective tissue) into an enucleated oocyte (49). There is currently much focus on the creation of controversial but revolutionary interspecies hybrid embryos where the nucleus from a human somatic cells are implanted into an enucleated egg cell of another animal (50). The resulting embryo (known as a chimera) will be almost completely human genotype but will have genome from the other animal (48). In 2003, scientists at the Shanghai Second Medical University fused human cell with rabbit eggs creating the first human-rabbit hybrid using the nucleus transfer technique. The hybrid embryo developed in culture for a few days before it was destroyed and the stem cells harvested (47,48). The purpose of the research into creating hybrid embryos is to provide researchers with human stem cells for experimentation into cures for diseases such as cystic fibrosis, Alzheimer’s and Motor Neuron disease as human stem cell are difficult to obtain (50).

[[File:Rabbit clone.jpg|center|450 px|thumb|(A) Cloned rabbits (5 month old) from nuclear transfer technique. (B) The male rabbit whose fibroblasts were used as the nuclear donors. The cloned rabbits have almost identical genome to the male donor.]]

'''Stem Cells'''
[[File:HES.jpg|right|200 px|thumb|Human Embryonic Stem cell (hES).]]
[[File:Rabbit knee.jpg|right|200 px|thumb|Stem cell induced cartilage repair of knee in rabbit.]]

Stem cells are unspecialized cells which are able to continuously reproduce themselves and under appropriate conditions, differentiate into all the various specialized cells of the organism such as cardiac cells, neurons and blood cells (39,40). Adults have a small number of stem cells when compared to a developing embryo and the stem cell of an embryo more easily obtained (41). Human embryonic stem cells (hES) derived from the inner mass of the preimplantation blastocyst have the potential to differentiate into all cell types in the human body and thus are valued by researchers (50). However, due to ethical and political issues, the obtaining and experimentation on human embryonic stem cells is difficult and alternate means are needed as stem cell provides potentially new treatments for a range of diseases (54).

Rabbits can be used both in the obtaining of stem cell for experimentation and also as recipients of stem cells to cure diseases. The human-rabbit hybrid embryo provides a method of obtaining stem cells for experimentation and these stem cells possess many similar properties to human stem cells, including expression of surface markers, special growth requirements, capabilities of self renewal, formation of embryonic body and differentiation into cells of all three germ layers (53).

Stem cell experimentation on rabbits also focuses on transplanting stem cell into rabbits to treat specific diseases. A study at Zhejiang University where a research team transplanted human mesenchymal stem cell into New Zealand white rabbits with myocardial infarction recoded regeneration of vascular structure and improvement in cardiac function. The research team noted the potential of stem cells in differentiating into specialized cardiac cells when subjected to the specific conditions of the rabbit heart (52).

Another study at Hallym University tested the effectiveness of transplanting mesenchymal stem cells from New Zealand white rabbits into damaged cartilage in the knees of other New Zealand white rabbits. In the experiment, mesenchymal stem cells were obtained from the rabbit bone marrow and injected into the knees of other rabbits that had cartilage in their knees surgically damaged. The research team were able to conclude notable cartilage recovery in the rabbits with the mesenchymal stem cell injection and the potential of mesenchymal stem cells to differentiate into fibroblasts, adipoblasts, osteoblasts and chondroblasts (51,53).

The findings in stem cell experimentation with in rabbits yielded positive results and potentially opens a new field of research in the use of stem cell to treat a range of diseases in humans.

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# Kondo, M, Sakai, T, & Ueno, S (2009). Generation of a Transgenic Rabbit Model of Retinal Degeneration. Investigative Ophthalmology and Visual Science, 50. Retrieved from [http://www.iovs.org/cgi]
# Punzo, C, Chen, B, & Roesch, K (2009). PHOTORECEPTOR DEATH IN MOUSE MODELS OF RETINITIS PIGMENTOSA. Retrieved from [http://genepath.med.harvard.edu]
# Zimmer, M (2008). Alba. Retrieved from [http://www.conncoll.edu/ccacad/zimmer/GFP-ww/cooluses8.html]
# Scott, C (2006, May 1). Chimeras in the crosshairs. Nature Biotechnology , 24, Retrieved from [http://www.nature.com/nbt/journal/v24/n5/abs/nbt0506-487.html]
# Mott, M (2005, January 25). Animal-Human Hybrids Spark Controversy. National Geographic News, Retrieved from [http://theyfly.com/PDF/Nat.%20Geo.%20Animal-Human%20Hybrids.pdf]
# Li, S, & Chen X (2006). Rabbits generated from fibroblasts through nuclear transfer . Society for Reproduction and Fertility, 131. Retrieved from [http://www.reproduction-online.org/cgi/reprint/131/6/1085]
# Minger, S (2007). Interspecies SCNT derived human embryos. Regenerative Medicine, 2(2), Retrieved from [http://www.futuremedicine.com]
# Koga, H, Shimaya, M, & Muneta, T (2008). Local adherent technique for transplanting mesenchymal stem cells as a potential treatment of cartilage defect. Arthritis Research & Therapy, 10(4), Retrieved from [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2575632]
# Wang, J, Li, C, & Sun, Y (2005). Human bone marrow-derived mesenchymal stem cells transplanted into damaged rabbit heart to improve heart function. Journal of Zhejiang University Science, 6(4), Retrieved from [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1389731]
# Chen, Y, Liu, A, & Mao, W (2003). Embryonic stem cells generated by nuclear transfer of human somatic nuclei into rabbit oocytes. Cell Research , 13(4), Retrieved from [http://www.nature.com]
# Bethesda (2009, September 23). Stem Cell Information. Retrieved from [http://stemcells.nih.gov]
# Cibelli, J. B. (2002). Principles of cloning Amsterdam. Academic Press
# European rabbit (oryctolagus cuniculus) Retrieved 9/21/2009, 2009, from http://www.feral.org.au/content/species/rabbit.cfm
# Warner, S. (2003). Inositol transport in preimplantation rabbit embryos: Effects of embryo stage, sodium, osmolality and metabolic inhibitors Reproduction, 125(4), 479-493.
# Derelanko, M. J. (2008). The toxicologist's pocket handbook, second edition Informa HealthCare
# Beaudoin, S., Barbet, P., & Bargy, F. (2003). Developmental stages in the rabbit embryo: Guidelines to choose an appropriate experimental model Fetal Diagnosis and Therapy, 18(6), 422-427.

==Glossary==

Anesthetic - A drug that causes temporary loss of bodily sensations

Aplasia - The absence or defective development of a tissue or organ

Blastocyst - A stage of embryo development that occurs about five days after fertilisation when the embryo contains quite a few cells

Caudal - Situated towards the inferior or posterior end of the body

Cephalic - Relating to the head

Cerebral Aqueduct - A canal filled with cerebrospinal fluid within the midbrain

Cerebral Cortex - The layer of unmyelinated neurons (the grey matter) forming the cortex of the cerebrum of the brain

Cerebro Spinal Fluid (CSF) - A watery fluid which flows in the cavities within the brain and around the surface of the brain and spinal cord

Chromosome - Microscopic carriers of genetic material, composed of deoxyribonucleic acid (DNA) and proteins and appearing as rods under a microscope

Cisterna Magna - is one of three principal openings in the subarachnoid space between the arachnoid and pia mater layers of the meninges surrounding the brain

Diploid - A full set of genetic material, consisting of paired chromosomes one chromosome from each parental set

Dorsal - Position towards the back

Fontanel - Membranous gap between the bones of the cranium in an infant or fetus

Genome - All genetic information, the entire genetic complement and all of the hereditary material possessed by an organism. Made up of both chromosomal genome (inside the nucleus of the cell in the familiar form of chromosomes) and mitochondrial genome (outside the nucleus in the cytoplasm of the cell, usually in the form of one round chromosome (the mitochondrial chromosome))

Genotype - The genetic makeup of an organism

Glucocorticoids - A class of steroid hormones that bind to the glucocorticoid receptor (GR), which is present in almost every vertebrate

Haploid - A single set of chromosomes (half the full set of genetic material)

Laparotomy- Surgical incision into the abdominal wall; often done to examine abdominal organs

Ligases - Group of enzymes that catalyze the binding of two molecules

Oocyte - A female gametocyte that develops into an ovum after two meiotic divisions

Phenotype - The observable traits or characteristics of an organism, for example hair color, weight, or the presence or absence of a disease.

Pronuclear - Haploid nucleus before fusion of nuclei in fertilisation

Restriction Endonucleases - Enzymes that recognize and cleave specific DNA sequences, generating either blunt or single-stranded (sticky) ends

Retina - The thin layer of cells at the back of the eyeball where light is converted into neural signals sent to the brain

Rostral - Situated toward the oral and nasal region

Somite - Blocks of mesoderm on either side of the notochord and neural tube during development of the vertebrate embryo. Develop into muscles and vertebrae

Stenosis - Abnormal narrowing of a bodily canal or passageway

Weaning - Young become accustom to nourishment other than suckling

==Links to Research Laboratories and Researchers==

1) Transgenic lab: [http://www.dnavision.be/index.php]

Involved in development of transgenic organisms, DNA construction and phenotype analysis.

2) World Rabbit Science Association: (WRSA) [http://world-rabbit-science.com]

International Association where researchers exchange knowledge and encourage teaching, scientific research, practical experimentation, the collection and publication of statistics and documents relating to the rabbit. Even have their own journal called “World Rabbit Science”

Website provides contact with researchers, professors and veterinarians working with rabbits.

Example: Dr. Myriam Kaplan-Pasternak, Doctorate Veterinary Medicine, University of California, myriamsemail@gmail.com

3) American Veterinary Medical Association [http://www.avma.org]

The American Veterinary Medical Association (AVMA), established in 1863, is a not-for-profit association representing more than 78,000 veterinarians working in private and corporate practice, government, industry, academia, and uniformed services. Excellent website into animal research and has a range of veterinary journals.

{{Template:Projects09}}
[[Category:Rabbit]]
[[File:Example.jpg]]

Talk:2009 Group Project 1

2009-10-14T11:53:05Z

Z3185685: /* Actual Changes Made */

== Lab 10 ==
--[[User:Z3283499|Antonio Lee]] 10:52, 2 October 2009 (EST) Hi everyone, I will be working with you during the Lab10 Tutorial and here is the news link and PDF of the manuscript for your group exercise. I encourage you to read the paper before the tutorial. Also, please indicate next to the questions below (using either your initials or student number) which one of the four questions you wish to address.
:'''Group 1 :''' [http://www.nature.com/nature/journal/v461/n7262/full/461354a.html '''Developmental biology: Asexual healing'''] in Nature News and Views - Nature 461, 354-355 (17 September 2009) [[Media:ANAT2341_Lab10_2009_Group 1 Reading.pdf|Manuscript (PDF): Mitochondrial gene replacement in primate offspring and embryonic stem cells]]

:Question 1. What is the background to the existing problem / disease condition? --[[User:Z3187802|Vishnnu Shanmugam]] 22:12, 2 October 2009 (EST)

Mitochondria are found in all eukaryotic cells and contain their own genome (mitochondrial DNA or mtDNA). Unlike the nuclear genome, which is derived from both the egg and sperm at fertilization, the mtDNA in the embryo is derived almost exclusively from the egg; it is of maternal origin.

Mutations in mitochondrial DNA (mtDNA) can lead to a range of chronic incurable diseases such as myopathies, neurodegenerative diseases, diabetes, cancer and infertility. Mutations in mitochondrial DNA could also contribute to other diseases such as Alzheimer’s,
Parkinson’s and Huntington’s diseases

A normal cell should be homoplasmic in its mitochondrial DNA, that is it should only contain one type of mitochondrial DNA. But if the cell has two or more types of mitochondrial DNA (a mixture of normal and mutated DNA) it is known as heteroplasmic and can lead to a range of diseases. These genetic mutations can also be passed to offspring causing disease.
1 in 3,500–6,000 are at risk or presently have a disorder from mutations in mitochondrial DNA. Disease progresses slowly and there are no cure. Limitations in assessing the extent heteroplasmy and accuracy in calculating the risks of developing mtDNA related disease means that a new approach is needed to tackle the problem.

:Question 2. What approach / method did the research team take to tackle / improve the problem?--[[User:Z3126328|Jin Lee]] 12:31, 7 October 2009 (EST)
:Working with rhesus macaque monkeys, the authors reconstructed mature oocytes containing the nuclear genome from one oocyte and the mitochondrial genome from another. To do this they removed the nuclear genetic material from one oocyte, leaving behind all of the mitochondrial DNA, then transferred it to another oocyte whose nucleus had been removed (a cytoplast), but which contained a full complement of mitochondrial DNA.

:Question 3. What was the breakthrough / major advancement OR failure / drawback? and why might this be of significance?
::Drawbacks - --[[User:Z3186093|Jenny Guy]] 22:43, 7 October 2009 (EST)
:::There were difficulties in visualising and isolating the intact chromosomes, as well as the mtDNA being susceptible to damage and translocation/movement. Visualization became easier after the development of techniques for DNA staining with fluorophores and looking under UV light during embryo cloning by the SCNT (somatic cell nuclear transfer). Successful implementation to avoid damage to the cytoplast during spindle removal involved using polarized microscopy. (p368) --[[User:Z3186093|Jenny Guy]] 14:12, 8 October 2009 (EST)
:Question 4. What are the next steps in moving forward? What are the next or new hurdles to overcome?

==Actual Changes Made==

'''Concise Version:''' (Everyone add their changes here)
# Removed cleft palate and cleft lip section (Abnormal development) --[[User:Z3187802|Vishnnu Shanmugam]]
# Altered references (current research and abnormal development) --[[User:Z3187802|Vishnnu Shanmugam]]
# Added picture guide for transgenic rabbit --[[User:Z3187802|Vishnnu Shanmugam]]
# Added picture guide for rabbit cloning --[[User:Z3187802|Vishnnu Shanmugam]]
# Removed newspaper image of rabbit (Current research) --[[User:Z3187802|Vishnnu Shanmugam]]
# Formatted pictures and text to reduce gaps in the assignment (current research and abnormal development) --[[User:Z3187802|Vishnnu Shanmugam]]
# Corrected spelling mistakes in images (current research and abnormal development) --[[User:Z3187802|Vishnnu Shanmugam]]
# Reviewed all images and have written a summary, original source, copyright information (current research and abnormal development) --[[User:Z3187802|Vishnnu Shanmugam]]
# Formatted the look of the genetics section, including 'abnormalities' --[[User:Z3186093|Jenny Guy]] 16:31, 14 October 2009 (EST)
# Fiddled with position of images in genetics section --[[User:Z3186093|Jenny Guy]] 16:31, 14 October 2009 (EST)
# Fixed spelling mistake in History - Jin Lee
# Added images in table of stages. --[[User:Z3185685|Sumaiya Rahman]]

'''Long Version:'''

--[[User:Z3187802|Vishnnu Shanmugam]] 23:46, 10 October 2009 (EST) Okies, all done. I'm going to review all my images and add summaries to them. Dr. Hill asked for a concise version to all the changes we make from the peer review process. I suggest everyone add their changes to the list I have started above and place your signature next to it.

--[[User:Z3186093|Jenny Guy]] 14:29, 10 October 2009 (EST)Hey vishnuu, i was thinking could you please alter
* the gaps between the spina bifida images (format this somehow with the images on the side and text on the other)
* the gap under "Brachydactylia & Acheiropodia"...maybe you have entered down too much????
cheers :)

--[[User:Z3187802|Vishnnu Shanmugam]] 21:27, 9 October 2009 (EST)Hey all. I have removed the newspaper image of rabbit (Due to copyright issues), and have replaced it with a series of images that guides the reader through the process of cloning a rabbit. I have NOT altered the text summarizing the creation of transgenic and clone rabbits as there are very important & detailed information which if removed puts complex processes in danger of oversimplification. I also corrected spelling mistakes in some images.

--[[User:Z3187802|Vishnnu Shanmugam]] 20:22, 7 October 2009 (EST) Hey gang. By popular demand (or the stress of reading) people want less text. I have removed the entire cleft palate & cleft lip section from abnormal development. For current research, I have also created a step by step picture guide for transgenic rabbit creation. It was initially meant to be a video, but this wiki page does not display (.gif) or (.mov) files. Sum, I remember that you did your references after me...so when I removed the cleft palate & cleft lip section, the references changed....so I have also adjusted your references accordingly. I don't think it is necessary to make all the changes outlined below as most comments are subjective (different people have different preferences) and seems like some comments were made because people had nothing else to propose.

--[[User:Z3126328|Jin Lee]] 10:01, 8 October 2009 (EST)Hi Guys, I have fixed spelling mistake and some people commented to make table form for advantages and disvantages section. But I liked the way I presented so I will leave in point form.

--[[User:Z3186093|Jenny Guy]] 14:32, 8 October 2009 (EST)
Hey! I looked at what i could change in the genetics section and decided to format a little. Our peers asked:
* genome information into a table - this is a little silly since there'd only be one column.
* Reformating in sections such as hitory and genetics. - have tried to do a little.
* Make pictures appear on the same side of page. maybe aligning the pics on either the left or right side instead of both left and right, and possibly putting them as thumbnails could also work. - i tried to put both of the chromosome images ont he same side (tried both left and right) but found that it looked terrible considering the size (which is needed to see it) as the text wouldnt fit around it very well.
* it will look much better if there is some work to be done for the structure of it especially the paragraph under the heading of 'abnormalities'. - am still in the process. not sure what else i can do since its in basic dot point form with not a large text to format. any ideas? or shall i leave it how it is now?
* maybe instead of writing the entire reference, you could just state The Broad Institute or just the people related to it - i feel that the entire team needs a mention since all people relate to it. noting just the broad institute is almost like noting a team of people here in unsw as just plainly "UNSW" which is just disrespectful.

==Things to work on noted by peers==

Hey, So the changes i will make will be in the introduction section. Also a lot of people have said to add pictures in the stages section to make it more interesting. I couldnt get permission to use the images so i bought tracing paper today! lol will try to draw them and see if they are ok enough to add. I think i am going to leave the timeline section as is because most people liked it. What do u guys think? --[[User:Z3185685|Sumaiya Rahman]] 15:31, 8 October 2009 (EST)

Sounds great Sum....Its gonna take some effort to trace it then scan it. GL --[[User:Z3187802|Vishnnu Shanmugam]] 21:37, 9 October 2009 (EST)

Hey guys,
I read through all the notes our peers have given us and summarised them into the following sections. Majority of them overlap (where ive put a new persons opinions in the same dot point over and over to stress the point on how many people noticed). Some things are easily changed, most of all i reckon its
# formatting
# pictures
# text to be more concise
So we just need to finalise all these minor things to improve our project. Please detail any changes you've made in the the heading above.
Cheers, --[[User:Z3186093|Jenny Guy]] 20:30, 7 October 2009 (EST)

INTRODUCTION
* a little too brief, more information needed
* For the first sentence (the characteristics that make the rabbit an excellent model for study), mention the section 'Why are we using rabbits?' under History section.
* For the second sentence (study that developed and improved micromanipulation techniques), mention the 'Transgenic Rabbit' section below under the genetics section. I've read the entire project page, and the introduction was the only place I found that was not precise enough (which is a great thing). These are minor things, but I think they will help with improving your project page.
*suggestion: Place the history section after the Introduction. This gives the viewer an overview of the use of the rabbit embryo. This way the viewer is first subjected to a few examples of the rabbit embryos use. It also allows him/her to understand where the rabbit embryo sits in with history. I guess this is a matter of personal preference.

HISTORY
* The advantages and Disadvantages would be better in a table. the history you might want to put the advantages and disadvantages into a table to make the page look a bit more tidy and easier to read when we go through it.
* The usage of rabbits for experimental models in science and medicine could be stated under the history section to allow background information for the readers to become aware of the topic and why the rabbit have been used to study specfic medical procedures and diseases.
* Spelling mistake under 'Discovery of Graafian Follicle', 2nd paragraph. I think it's previous instead of 'previcous'.
* Reformating in sections such as hitory and genetics. Make pictures appear on the same side of page.
* The history section can be improved if the infomation is expanded to give some more detailed background knowledge although i like the idea that the information is concise describing each scientists contribution towards the model.
* could be formatted to make the information stand out and a lot more appealing, I would recommend including pictures if possible that link to the text and making the advantages and disadvantages into a table rather than listing it.

TIMELINE
* more images to wholly understand. timeline/staging section was clear and concise, however it could be improved by adding more colour/pictures to maintain the readers' interest. The timeline and staging bits are very well written and clear but i think you should add a few images in there to match up with the text. Perhaps some pictures of embryos throughout development. Pictures for every stage would make it more visually attractive rather than just reading text. lack of pics in the timeline.
* It’s a little confusing that the development jumps back and forth according to the body part developing. Maybe it should be categorised according to time of development instead for greater clarity at first glance
* The timeline is just a little confusing, as its divided into development of different parts, which breaks the time flow.
* some of the information for the timeline section was too heavy for the page - would recommend only using some of the information on your actual page and having the rest as links to separate pages

STAGING
* pictures for stages would have been nice, unless there were none????
* a more even distribution of information, particularly more detail in the stages
* Provide pictures for individual stages. Get visual, and make the stages interesting to read. include pictures in the stages section.
* Staging section is also very well presented but the information presented in a table would even look better if there is use of some pictures to make it more interesting for its audience.
* staging section was very bland and would be more appealing with pictures. I dont think its necessary to cite your entire reference within the text

GENETICS
* genome information into a table
* Reformating in sections such as hitory and genetics.
* Make pictures appear on the same side of page. maybe aligning the pics on either the left or right side instead of both left and right, and possibly putting them as thumbnails could also work.
* it will look much better if there is some work to be done for the structure of it especially the paragraph under the heading of 'abnormalities'.
* maybe instead of writing the entire reference, you could just state The Broad Institute or just the people related to it

ABNORMAL DEVELOPMENT
* There is also a lot of content which might be alleviated by reducing the section on abnormal development. Too much information about the abnormalities. make more concise.
* the abnormalities went a bit over board, and didn't need that much attention I think (as compared witht the research which was good)
* reduce the writing content. for example. In the current research section, you have two scientific process of transgenic rabbits as well as cloning which is described in how these are done. why not draw a step by step diagram, and put these written steps in the link to the image.
* The information provided under Hydrocephalus and Brachydactylia was informative and interesting, but it contained too much text. I suggest you narrow it down and make use of Dots point, numbering, bold/italic words, and/or sub-sub-headings.
* Section for "Abnormal Development" gives the readers useful amount of information but i think its very lenghty, use of dot points can make it look even better and easy to understand.

CURRENT RESEARCH
* the group makes good usage of diagrams but towards the end diagrams die out, you might want to make the current research part of your assignment into diagrams and steps as there is just a bunch of information thrown there and alot of reading needed, if you put it into steps or diagrams it will make the marking process and reading process easier and allow us as reader to understand the information with ease.
* 'Transgenic Rabbit' should be shifted toward the genetic information on the rabbit. (Jenny - i dont agree with this as its research, not its offical genetics. Vishnnu - Neither do I)
* information in regard to stem cells should be brief and truncated. Example in regard to stem cell research should have brief and simple model explaining the process and why it used.
* There is too much information under stem cells. There is 2 examples of studies dealing with stem cells. A suggestion would be to just have one, and have a link saying 'Koga's research on Stem Cells'.
* Have the section 'links to Research labs and researchers' placed at the end of current research. That way, the information on the page will flow smoother.
* more of a focus on current research i.e. what each method is being used for and less on the process behind each method.
* great amount of information but in my perspective replacing the paragraphs with some dot points with heading and subheadings would further enrich understanding of readers.

OVERALL
* "As you start going down the page though the information starts to read a bit haphazardly, for example the developing body; jumping for section to section and the timeline section. it would be great if you could clean this up as it doesn't really flow." - formatting
* condense long slabs of text as the page is long
* format it so there are no huge gaps
* move the links to current research labs up closer to the current research section, just to keep it all together

==Constructive Criticism of Coordinator==
--[[User:S8600021|Mark Hill]] 08:07, 8 October 2009 (EST) The following comments are general in nature in no specific order, as it would be inappropriate to suggest specific changes and then assess the final project. Comments will be added during this week and you still have one week before final submission.

* There is no concise list of changes made to your project on the basis of peer assessments.
* Timeline of Embryo Development early stages, are in the introductory text said to be in hours, but it would be good to see it in the list as well.
* [[:File:Sizes.JPG]] Relative sizes, but no absolute size or scale given.
* A general comment about images. When you click an image and it opens, the information below the image should have an explanation of what the image shows, a reference (if from a paper) and a link to the original source (if available) as well as copyright information.
* Did you actually read the terms of use for this image that you cut n pated into the image description? [[:File:Rabbit_hybrid.jpg]] "For this purpose alone you may retrieve and display the Content on a computer screen. You may also print out, but not photocopy, one copy of individual files on paper and store files in electronic form on disc, but not on any server or any other storage device connected to a network where the Content could be accessed by other users." It clearly states that you cannot use this image online.
* Chromosomes section, images have no legends and structure not clearly organised.
* There needs to be better checking of your spelling and grammar, for example [[:File:Rabbitmalformation3.jpg]] "Plant Patkology of Tke Rockefeller Institute for Medical Researck", these mistakes while not major, suggests a lack of reviewing of your work by the group.
* Just a comment on project "feel", when several people work together on a project and insert their parts, the final project sometimes has an uneven style. Now that you have time to tidy up, try and get a common appearance throughout your project.

==Constructive Criticism of Peers==

--[[User:Z3218657|Sally Clarke]] 09:32, 1 October 2009 (EST)
Nice work Guys!
- Fantastic images used throughout - maybe a few more in the timeline so we can understand what is going on
- As you start going down the page though the information starts to read a bit haphazardly, for example the developing body; jumping for section to section and the timeline section. it would be great if you could clean this up as it doesn't really flow.
- The section on the abnormal development is great.
- The page is quite long - Maybe you could condense some of the text as it is kind of slab like
- i really enjoyed the breeding section
- The advantages and Disadvantages would be better in a table.

--[[User:Z3223194|Bronwyn Lewis-Jones]] 08:08, 1 October 2009 (EST) Hi Group 1! This is obviously a well organised and well researched assignment. I found it very informative. There are (of course) some things I feel could improve the overall submission. I loved that the timeline/staging section was clear and concise, however I think it could be improved by adding more colour/pictures to maintain the readers' interest. There is also a lot of content which might be alleviated by reducing the section on abnormal development. Hope this helps :)

--[[User:Z3218146|Julianna Lam]] 01:11, 1 October 2009 (EST) good job guys.
-Theres alot of relevant information.
-The timeline and staging bits are very well written and clear but i think you should add a few images in there to match up with the text.
-The image for the genetics bit is awesome.
-The page is nicely set out.
-Too much information about the abnormalities.

--[[User:Z3258567|Sando Rashed]] 20:04, 30 September 2009 (EST)hey guys, your page looks good, starts off well as there is not a bunch of information just thrown in, the information used is well thought, with the history you might want to put the advantages and disadvantages into a table to make the page look a bit more tidy and easier to read when we go through it (you can also do this with the info under genome), the group makes good usage of diagrams but towards the end diagrams die out, you might want to make the current research part of your assignment into diagrams and steps as there is just a bunch of information thrown there and alot of reading needed, if you put it into steps or diagrams it will make the marking process and reading process easier and allow us as reader to understand the information with ease, other than that the page looks quite good, well done on all your contributions

--[[User:Z3218792|Gabriela Pinget]] 21:51, 29 September 2009 (EST)

Nice page. I particularly liked the idea of lists of what is to come before each flood of information as was done with the ‘history of model use’ section.

- Nice easing into the topic with ‘advantages’ and ‘disadvantages’ lists.

- I liked the of rabbit embryo development to that of humans- puts it into perspective

- Good glossary- informative but not over- the- top

- Nice genetics section! Easy to read and a great use of illustrations to break up the information

- I also like that you took a page out of Mark’s book in the addition of the abnormalities section

Improvements:

- Perhaps some pictures of embryos throughout development.

- It’s a little confusing that the development jumps back and forth according to the body part developing. Maybe it should be categorised according to time of development instead for greater clarity at first glance

--[[User:Z3295026|Joe Nassif]] 17:01, 29 September 2009 (EST)

Your assessment has come along great in regard to the criteria format. There are a few alterations that could improve your project, the following alterations may enhance your wiki page:

'''-''' The usage of rabbits for experimental models in both science and medicine could be state under the history section to allow background information for the readers to become aware of the topic and why the rabbit have been used to study specfic medical procedures and diseases.

'''-''' Secondly the information on 'Transgenic Rabbit' should be shifted toward the genetic information on the rabbit. So far the project is looking and coming along great except for minor edits.

'''-''' Background information should be placed subsequent to the introduction allowing the reader to understand why this specific animal is used for specfic purposes.

'''-''' Figures/Graphs and the illustration of the anatomy and genetic development of the embryo were useful and clear allowing the viwers to understand and learn through the demonstration of pictures which were extremely informative.

'''-''' Genetics: the Genetics and Abnormalities information was great and very informative. It was great how the group compared the embryo with the human chromosome allowing the audience to understand the difference between both.

'''-''' Abnormalities: Information and details which were in the genetic section provided informative and interesting information, and it could be truncated a bit, additionally just discussing the chromosome development of the rabbit.

'''-''' Current Embryology Research: information in regard to stem cells should be brief and truncated. Example in regard to stem cell research should have brief and simple model explaining the process and why it used.

'''-''' Consequently, I thought the project was good it flowed and was very informative. The information was detailed, and the illustrations were useful and allowed the readers to gain a brief overview on the topic and it usage in history and in current research. Overall group 1 seem to achieve the critriea outcomes and summarised the topic really well, the comparsion to human embryo development througout the text was great and is a good referencing point in comparsion to the species choosen.
Great job --[[User:Z3295026|Joe Nassif]] 17:01, 29 September 2009 (EST)

--[[User:Z3255007|Sadaf Masood]] 12:09, 30 September 2009 (EST)Hello Group 1! Congrats on your awesome group project! I must say im very impressed with all the information you have posted and i have listed down the good bits and the bits that need to be improved. Since i am posting this a lil late, i have seen that u have already improved your project and few aspects...Good Job guys!

1. Very brief introduction...maybe just a little bit more info will be perfect

2. Abnormalities section is very informative and well researched, but very long, how about making it a little more precise?

3. The Advantages and Disadvantages of the using Rabbit is just simply perfect

4. The timeline is just a little confusing, as its divided into development of different parts, which breaks the time flow.

5. Pictures for every stage would make it more visually attractive rather than just reading text

6. Great Glossary!

There were few things earlier that need to be improved but you guys fixed it as soon as comments were posted so basically you guys rock :)An excellent effort guys. Best Wishes

# --[[User:Z3217015|Mitchell Mathieson]] 09:45, 25 September 2009 (EST)Very nice. The information was maybe a bit spread out, with heaps of gaps everywhere (formatting???), but the information was there, and relevant, and easy to read. I like how there was tonnes of information on current research, as I think that was the main aim, but the abnormalities went a bit over board, and didn't need that much attention I think. pictures for stages would have been nice, unless there were none???? The references are top notch, and the glossary is pretty amazing, and in the right place. Overall very good, I think formatting was the major downfall though, as it makes the page that much longer, and hence a little bit more difficult to read.

--[[User:Z3224449|Elide Newton]] 14:12, 26 September 2009 (EST)
HEllO GROUP 1: Well done on such a great assignemnt, looks like you have all worked very hard. Well my one point of constructive criticism would be to reduce the writing content. for example. In the current research section, you have two scientific process of transgenic rabbits as well as cloning which is described in how these are done. why not draw a step by step diagram, and put these written steps in the link to the image. that way it is more visual, the info is still there under the image link, and the page wont look as daunting to read. :) hope this helps!

--[[User:Z3254857|Begum Sonmez]] 00:46, 26 September 2009 (EST)
Hello Group 1. Firstly, I would like to let you all know that you have all done a great job. I'm impressed. I have a few suggestions that I think mite help to improve the page even more:

*Introduction:

1)For the first sentence (the characteristics that make the rabbit an excellent model for study), mention the section 'Why are we using rabbits?' under History section.

2)For the second sentence (study that developed and improved micromanipulation techniques), mention the 'Transgenic Rabbit' section below under the genetics section. I've read the entire project page, and the introduction was the only place I found that was not precise enough (which is a great thing). These are minor things, but I think they will help with improving your project page.

3)Breeding information was informative.

4) A suggestion: Place the history section after the Introduction. This gives the viewer an overview of the use of the rabbit embryo. This way the viewer is first subjected to a few examples of the rabbit embryos use. It also allows him/her to understand where the rabbit embryo sits in with history. I guess this is a matter of personal preference.

*Timeline:

1)Graphs, and the illustration of the zona pellucida and mucin coat were very clear and informative.

*Staging: I had no problems with it. The lack of information I think was a plus. It touched on the content in the Timeline section.

*History:

1) I loved the idea of the 'Disadvantages' of the rabbit embryo, it seemed unbiased. The brief timeline provided a clear and short summary.

2) Spelling mistake under 'Discovery of Graafian Follicle', 2nd paragraph. I think it's previous instead of 'previcous'. Also, the 2nd paragraph under this heading does not flow that well. Try rephrasing the 2nd sentence.

*Genetics:

The Genetics and Abnormalities section flow into eachother very well. I appreciated the comparison of the rabbit chromosome to the human chromosome.

*Abnormalities:

1) The information provided under Hydrocephalus and Brachydactylia was informative and interesting, but it contained too much text. I suggest you narrow it down and make use of Dots point, numbering, bold/italic words, and/or sub-sub-headings.

*Current Embryology Research:
1) There is too much information under stem cells. There is 2 examples of studies dealing with stem cells. A suggestion would be to just have one, and have a link saying 'Koga's research on Stem Cells'.

2) Have the section 'links to Research labs and researchers' placed at the end of current research. That way, the information on the page will flow smoother.

Overall, I thought there was a consistent structure in each section. The information was informative, and the pictures were relevant and helped me better understand the topics of discussion.

--[[User:Z3252340|Emily Wong]] 10:58, 27 September 2009 (EST) Firstly, great work. It is a well researched, structured and organised page. The content is very in depth and includes information on all of the specified areas. It is well referenced, with an extensive reference list indicating the amount of research put into the page. Some areas are more detailed than others. For example, the staging section is quite short and concise where as the Abnormal development section is extremely long considering it is not a needed topic. There is moderate use of pictures and diagrams, but more use could benefit the page as it may be able to negate some of the large slabs of text. The comparisons made between the human and the rabbit embryos are a good part of the project page. Each member of the group has contributed to the page and provided a lot of information on the section of content they were working on. What would improve this project is a more even distribution of information, particularly more detail in the stages, a few more diagrams or pictures to negate some of the text presented, more of a focus on current research i.e. what each method is being used for and less on the process behind each method.

--[[User:Z3126345|Gang Liu]] 14:26, 27 September 2009 (EST)In my opionion, this is a well constructed page. It includes major subheadings such as history, timeline, stages, genetics and current research. It is very concise and straightforward, which makes it easy to read. For example, a short introduction paragraph,"...the rabbit is an appropriate animal model as the results from many experiments are significant to that of other mammals, including humans.", explains to reader why rabbit is such a suitable model.

It also provides a logic flow. For example, in history of rabbit model use section, it has provided advangtages and disadvantages of model use. This is appropriate, as it demonstrates the significance of rabbit model use in scitific discovery. In addition, it has provided detailed background information for each discovery. This makes it interesting to read.

It is also important to compare development of embryo between rabbit and human. For example, "... the similarities of this developmental pattern in humans and rabbits, suggests that the same growth increment is required to achieve the same stage. The main difference observed between human rabbit gestational duration is due to the fetal growth phase...", this has suggested human and rabbit share many similarities. Not only this page has demonstrated detailed written information of timeline development, it also provided graphics to reinforce the concept. For example, the hand drawing of developing embryo. As well as the comparison between human embryo and rabbit embryo timeline development.

It is also interesting to learn that rabbits have 22 pairs of chromosome, whereas humans have 23 pairs of chromosome.

Sections such as abnormal development and current research have demonstrated extended research and understanding. For example, hydrocephalus, spina Bifida, stem cell research and cloning techniques. All of these have showed the in depth research in textbooks, journals and internet based literatures.

However, this page can be improved by considering the following points.

*Provide pictures for individual stages. Get visual, and make the stages interesting to read.

*Reformating in sections such as hitory and genetics. Make pictures appear on the same side of page.

*Typo: "A rabbits potential for reproduction..."

*Sections such as abnormal development and current research are too lengthy. Might consider shrink the content.

*Lack of glossary.

Overall, big thumbs up!

--[[User:Z3252231|Angama Yaquobi]] 01:12, 28 September 2009 (EST)
First of all i would like to congratulate all the team members for a great team work.
Well done guys!! The group project looks amazing, the information presented is very concise
and straight to the point which makes it very easy for the readers to grab
the important information that they need to enhance their knowledge.
I like the section of history, the information is very clear,
and i like the idea of providing some background knowledge to the readers
about the disadvantages of the use of rabbit.
The history section can be improved if the infomation is expanded
to give some more detailed background knowledge althought
i like the idea that the information is concise describing each
scientists contribution towards the model.
The section for timeline is impressive, in my perspective its a great idea to cover alot of content in a very smart way
which is by the use of subheadings to make it easy to understand for audience.
Staging section is also very well presented but the information presented
in a table would even look better if there is use of some pictures
to make it more interesting for its audience. Genetics section
is beautifully presented, all the information is there with some
amazing pictures but will look much better if there is some work to
be done for the structure of it especially the paragraph under the
heading of 'abnormalities'. Section for "Abnormal Development" gives
the readers useful amount of information but i think its very lenghty,
use of dot points can make it look even better and easy to understand.
The same for Current embryology research, great amount of information but
in my perspective replacing the paragraphs with some dot points with
heading and subheadings would further enrich understanding of readers.
Also glossary would complement the webpage. But overall,
great amount of information which shows alot of research
which has been done by all the team members. Well done guys!!

--[[User:Z3217686|Thomas Dangerfield]] 13:29, 28 September 2009 (EST) Hey guys! Good work on your assignment! Plenty of info which is good, and very well referenced. The glossary is a good idea too! I do agree with a few others about the lots of clear spaces in the formatting, and the lack of pics in the timeline though. Also under the genetics section, maybe aligning the pics on either the left or right side instead of both left and right, and possibly putting them as thumbnails could also work. In the abnormalities section, there might have been a little too much info that probably wasn't needed, but i do like the effort put in. Over all, possibly more time spent on formatting and determining which sections are more important and which sections may need to be limited. Other than those points, the whole assignment seemed very well done!

--[[User:Z3215682|Carly Mooney]] 11:32, 29 September 2009 (EST)
You assignment is visually appealing and the genetic information e.g. the number of chromosomes of a rabbit was very interesting.There are some additional sections you have added which really complement your assignment e.g the abnormalities and I really liked the advantages and disadvantages of using the rabbit model. The few suggestions I would make is to:
* include pictures in the stages section
*place the pictures throughout the text (e.g. to left or right). You did this up until abnormalities and I felt it broke the flow of the written text.
* and maybe move the links to current research labs up closer to the current research section, just to keep it all together.
Overall very impressive though.

--[[User:Z3220040|Joanne Raffel]] 15:25, 29 September 2009 (EST) Nice wikipage, the page looked interesting however I agree with some others that the formatting of the page was inconsistent. I thought the referencing was great but found it a bit confusing with the reference numbers after the paragraphs. I thought the subheadings werent distinct enough, especially in relation to the text, which made it difficult to read. The history section could be formatted to make the information stand out and a lot more appealing, I would recommend including pictures if possible that link to the text and making the advantages and disadvantages into a table rather than listing it. I especially liked the comparison between the rabbit and the human embryo, however some of the information for the timeline section was too heavy for the page, I would recommend only using some of the information on your actual page and having the rest as links to separate pages. The staging section was very bland and would be more appealing with pictures. I dont think its necessary to cite your entire reference within the text, especially in the genetics section, maybe instead of writing the entire reference, you could just state The Broad Institute or just the people related to it. The abnormalities section was a good inclusion however it was very extensive, along with the current research section. Overall a very good wikipage.

----
*Hey, Well done guys!!! I think our group worked pretty well! I think we communicated each other well and did very best for their section. I fixed my spelling mistake and problem with sentence! As Begum mentioned, I think placing the history part after the introduction is better idea. --[[User:Z3126328|Jin Lee]] 13:36, 26 September 2009 (EST)

*Hey guys,
the project has come together brilliantly! it looks quite good. Hopefully mark will like it! ill add some terms to the glossary and try do some formatting (the first image is a little too big i think!) --[[User:Z3186093|Jenny Guy]] 10:28, 24 September 2009 (EST)

Hey. Yep all good. I had to get rid of the pics, so stages table is now blank. Im pretty much done. I'll see what i can add to the glossary. thanks :)--[[User:Z3185685|Sumaiya Rahman]] 23:34, 23 September 2009 (EST)

Hey all, I'm going to start a glossary and add it under the reference section. Scan your text and add to the glossary in alphabetical order. Also under the marking criteria, it says to provide links to researchers and research laboratories.....i'll start that under the glossary. Everyone else OK with their stuff?--[[User:Z3187802|Vishnnu Shanmugam]] 23:08, 23 September 2009 (EST)

Hey Sum, The images look fine but I don't think you can use the images like that since the journal KARGER is being particular about its copyright laws. I tried tracing around the images but it does not seem to resemble anything like an embryo. I did however find this link...go to it and scroll down to the images of the developing embryo. You might be able to edit it to resemble rabbit embryo. --[[User:Z3187802|Vishnnu Shanmugam]] 15:10, 23 September 2009 (EST). To get to the link, Google image search "rabbit gestation"....click on the "rabbit,gestation age" image from nature.com
Also google image search "The Haeckel embryo sequence"...could be useful after some editing

oh my god!! I summarised all of my research and wrote down on the page. Then I blew up everything!!!
it says 'edit conflict' what da?? I lost all of my work...it was my stupid mistake...--[[User:Z3126328|Jin Lee]] 01:06, 23 September 2009 (EST)

Oh also.. let me know if the images look stupid --[[User:Z3185685|Sumaiya Rahman]] 00:34, 23 September 2009 (EST)

Hey thanks vishnuu. I put some images up in the stages table. I did edit the pictures, but im not sure if im allowed to use it like this? have a look and let me know. Also im not sure what is going on with the reference section seems kinda all over the place, so i havnt added mine in yet. Maybe we should fix that up somehow? :) oh LOL about the breeding rabbits bit! haha
--[[User:Z3185685|Sumaiya Rahman]] 00:31, 23 September 2009 (EST)

Hey Sum, Sorry for the late reply. For $330, I'd rather breed rabbits and take the photos myself. I had a look at the original images, what we can do is trace around the developing rabbit embryo using the pencil tool on an image editing software(eg. microsoft paint - already preloaded into most windows). Then upload the image to the assignment. Does your PC have adobe fireworks?...extremely good for tracing images. If not, have a go at it with microsoft paint....I shall also have a go at it, then I shall let you know on this discussion page at about 3PM t'morrow. If any good then I'll send it to your student email. If not, we discuss potential alternatives. good luck Sum! --[[User:Z3187802|Vishnnu Shanmugam]] 23:51, 22 September 2009 (EST)

Yep thats the article i used for the developmental stages and put in a table. I should have my timeline posted by end of today. I also couldn't get permission to use the pictures as they wanted about $330 for me to use it!! no thanks. I'll see if i can work it in somehow. Vishnuu did u have any ideas on editing the images?? --[[User:Z3185685|Sumaiya Rahman]] 12:29, 22 September 2009 (EST)

Have a look at this article, it's helpful for comparison bt rabbit and human in developmental stages!--[[User:Z3126328|Jin Lee]] 13:35, 21 September 2009 (EST)
*Sampled rabbit embryos were staged using the Carnegie criteria, in order first to determine if they were consistent with the rabbit developmental pattern, and second to compare this pattern with the human one. Our results show a suitable '''comparison of rabbits and humans in early developmental stages''', except for the neural growth.
[http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowAbstract&ArtikelNr=73136&Ausgabe=229537&ProduktNr=224239
]

Absolutely correct Juliana, my research articles and their links are labelled 1-6 so far, the rest is yours..... I'll fix it for you. A timeline image seems tricky and i'm unsure, send Dr. Hill an email on m.hill@unsw.edu.au and see what he says. We still have till thursday to finish everything, so don't be too worried....try to finish all your other stuff and leave the drawing of the timeline last.--[[User:Z3187802|Vishnnu Shanmugam]] 17:49, 20 September 2009 (EST)

*no.1-7 in reference section is mine. and I think links under Vishnnu's research on the discussion board is mine. let me know please. (I can't remember all of my researches)
I want to make a timeline image but I can't do it;;; I asked Mark few weeks ago but havn't replied yet....can somebody help me???--[[User:Z3126328|Jin Lee]] 17:26, 20 September 2009 (EST)

'''** Hey Jenny, dont worry!! the project is not due until next week! (24th) we will have it done by then!! I am still waiting for permission to use the pictures in my stages section, thats why it hasnt been done yet. Hopefully i can get permission, otherwise i'll have to draw them (or something) myself.''' --[[User:Z3185685|Sumaiya Rahman]] 14:03, 17 September 2009 (EST)

It says project due date 24th september.......if the due date had been brought forward why was it not posted on the project main page? --[[User:Z3187802|Vishnnu Shanmugam]] 13:48, 17 September 2009 (EST)

EVERYONE...WHY IS THE REST OF OUR PROJECT NOT DONE??
* vishnuu...its due TODAY!! how can you post things up next Monday? Please make sure youve referenced EVERY image and all text (i know youve said you need to do this...but its easiest done when writing the section as now you have to go back and find everything, insert numbers etc. Remember to put the reference in the reference section. For the current research section i thought this might help you (as during my lecture in another class they spoke about how rabbits are used in heart development. Is there anything that you've found to include this?). Also I found this website during my research so it may help you? [http://www.evergen.com/rabbit_experience.html/ Rabbit Experiments]
* sum - where is the timeline???? It doesn't exist? Where is it? Also, we need some sort of visual for the staging. Have you found an images? Could you draw the stages of embryo development? It just looks incredibly boring.
* julianna...you need to put up more other than just two historians...there is NO referencing whatsoever in your entire section. where have you found this information? have you put it in your own words or copied it? You need to add some more refences to the reference section at the bottom..there just aren't many to back up your research.

seriously guys. ive added photos and tried to spice up the project but i am NOT going to finish your sections for you. ITS DUE IN 3 HRS! i cant believe you guys haven't bothered to even try finish this. Im very disappointed and i think its slack to let the team down. --[[User:Z3186093|Jenny Guy]] 10:34, 17 September 2009 (EST)

----

Hey all, just need to finish editing the current research part before i post it up, also need to edit some of my images under abnormal development and also references. Should be all done by Monday. --[[User:Z3187802|Vishnnu Shanmugam]] 07:02, 17 September 2009 (EST)

--[[User:S8600021|Mark Hill]] 01:40, 8 September 2009 (EST) OK guys, this is still just a page of text......

--[[User:Z3126328|Jin Lee]] 14:50, 3 September 2009 (EST) I want to make a timeline?

--[[User:S8600021|Mark Hill]] 08:42, 21 August 2009 (EST) z3187802 has contacted me and has been away sick. He should still complete his components of the group project.

Our group is Sum, Vishnnu, Juliana and Jenny. Today in the lab we have decided to research the RABBIT! [http://embryology.med.unsw.edu.au/OtherEmb/Rabbit.htm/ Rabbit embryology from Mark Hill]

(Juliana's email belebele85@msn.com)

----
This is apparently what we need to include in our case study:
#Timeline of Embryo Development - how long (SUM)
#Staging - are there species specific staging, what occurs when (SUM)
#History of Model Use - when was it first used, (JULIANNA)
#Genetics - chromosome number, sequencing (JENNY)
#Abnormal Development (VISHNNU)
#Current Embryology Research - research papers and findings (VISHNNU)

Hey guys, maybe we should add a section comparing rabbit to human development
--[[User:Z3185685|Sumaiya Rahman]] 16:45, 6 August 2009 (EST)

That sounds like a good idea Sum....seeing that human development is the primary theme of the course, not including it would be criminal!. -vishnnu

Report:
* Links to resources and discussions are to be posted on the group talk page, the project page is for the actual assignment
* Final assignment will be marked by another group and everyone will be given a marking criteria
* No information should be obtained from Wikipedia and all information (tables & graphs included) must be referenced
* Please feel free to suggest any further topics which can be included

== Research: ==
So i think the main rabbit used in research is the oryctolagus cuniculus. Lets focus mostly on that (or at least i, Jenny, will since im going genetics). This link is great for the specific genetics: [http://www.ncbi.nlm.nih.gov/nuccore/AJ001588/ Oryctolagus cuniculus complete mitochondrial genome]

Here's some stuff about benefits of modeling from a textbook. I haven't yet written as my own so its still the authors material. Just thought it might benefit us all (and raise our morale as we thought the rabbit might suck..but it doesn't!) We're not "submitting" this as our own work so technically we're not yet copyrighting their material.
Ive cited the book here and the website i got it from:
[http://books.google.com.au/books?id=RY0rXE2HgqsC&pg=PA344&lpg=PA344&dq=rabbit+embryology+genetics&source=bl&ots=rbr3CuBRxY&sig=p8055w9oYQmsQeuN78mgXBGmRK4&hl=en&ei=NI2KStaQJIvSsQOEpMjEDQ&sa=X&oi=book_result&ct=result&resnum=3#v=onepage&q=&f=false/ Cibelli, J., Lanza, R., Campbell, K. and West, M. 2002. Principles of Cloning. Academic Press]

“Rabbits were one of the first species in which blastomere nuclear transfer succeeded; as a model species, rabbits placed a central role in developing the micromanipulation technologies in embryos.” Other advantages for using rabbits are:

# “The costs to animal procurement, animal care, and oocyte production in rabbits are relatively low compared to large animals.” e.g. a cow embryo is 30x more expensive that a rabbit embryo
# “The developmental biology of rabbit embryos and fetuses resembles more closely that of large farm animals than that of rodent model species, including the transition from maternal to embryonic control of embryo development.”
# “The pregnancy of rabbits is relatively short (1 month), allowing rapid evaluation of fetal and postnatal development. In comparison, the gestation length for cattle is 9x longer.”
# “The sizeable milk production of rabbits allows their use as test animals for therapeutic protein expression in milk, or as a living bioreactor.”
# “Rabbits are induced ovulators. Domesticated rabbits are nonseasonal breeders and produce multiple offspring in one litter. These reproductive patterns make the use of rabbits for reproductive research highly efficient.”

----
Here are some links i (sum) found which may help. Need to go through all the info and sort it out, But there are a couple of good diagrams.

'''Links for group assignment'''

http://www.reproduction-online.org/cgi/reprint/48/1/43

http://books.google.com/books?id=RY0rXE2HgqsC&pg=PA344&dq=rabbit+embryo+stages&as_brr=3#v=onepage&q=rabbit%20embryo%20stages&f=false - good for what studies in rabbit embryo have been used for. And has a good table for embryological stages!!

http://books.google.com/books?id=ljAKtC-iIrIC&pg=PA264&dq=rabbit+embryo+stages&as_brr=3#v=onepage&q=rabbit%20embryo%20stages&f=false

http://books.google.com/books?id=73bbKzqRvLsC&pg=PA156&dq=rabbit+embryo+stages&lr=&as_brr=3#v=onepage&q=rabbit%20embryo%20stages&f=false - picture of implantation

http://books.google.com/books?id=aZ7DQYFyxswC&pg=PA122&dq=%22rabbit+development+stages%22&lr=&as_brr=3#v=onepage&q=&f=false
-------
Hi I(Juliana) uploaded file, you guys can have a look.
Go to 'Upload File' tab and click ' early growth of rabbit trophoblast' file.

-------------
also I found an interesting article!
'''An Electron Microscope Study of the Embryology of the Intercalated Disc in the Heart of the Rabbit'''
Alan R. Muir
The Journal of Biophysical and Biochemical Cytology, Vol. 3, No. 2 (Mar. 25, 1957), pp. 193-202
Published by: The Rockefeller University Press

http://info.library.unsw.edu.au/cgi-bin/local/access/ej-access.cgi?url=http://links.jstor.org/sici?origin=sfx%3Asfx&sici=0095-9901(1957)3%3A2%3C193%3AAEMSOT%3E2.0.CO%3B2-S
--

[[User:Z3126328|Jin Lee]] 10:48, 25 August 2009 (EST)

----------------
I found helpful book in the library
'''Bensley's Practical Anatomy of the Rabbit 8thE by E.Horne Craigie, Toronto, University of Toronto Press 1948'''
--[[User:Z3126328|Jin Lee]] 13:27, 27 August 2009 (EST)

==Vishnnu's Research==

'''Background reading (Vishnnu)'''

Hey everyone. I'm starting my background reading section where I shall describe my research resources. They contain a summary and a link to the resource itself. I shall keep this "notes" section updated with each new entry I add.

'''Notes:'''

*Articles 1 & 2 - Juliana this could be useful to you.

*Article 2 - Sum this could be useful to you.

*Articles 3 & 4 - Abnormal development articles (added: 02/09/2009)

*Articles 5 & 6 - Abnormal development articles (added: 13/09/2009)

'''Article 1'''

'''The rabbit as a model for reproductive and developmental toxicity studies''' --[[User:Z3187802|Vishnnu Shanmugam]] 21:05, 30 August 2009 (EST)

''Robert H. Foote and Edward W. Carney'' ''Reproductive Toxicology 14 (2000) 477–493'' ''Department of Animal Science, Cornell University, 204 Morrison Hall, Ithaca, New York 14853-4801, USA Developmental and Reproductive Toxicology, ''The Dow Chemical Company Midland, Michigan 48674, USA''

'''Summary'''

This is a review article of a study looking at the use of rabbits in toxicological studies. The article describes the advantages in using the rabbit experimental model as opposed to the rodent model (mice & rats) and outlines the differences that make toxicological studies on rabbit embryos more accurate than rodents to resemble similar toxicological effects in human embryos. The article describes various techniques that can be used (eg. blood collection from marginal ear vein, artificial insemination, embryo collection) and solutions to some common problems that researchers face when using animal models. Very interesting article with a great quote from Robert Koch to open the eyes of researchers to other animal models:

“Gentlemen, never forget that mice are not human beings”

Want to find out more? Follow the link!

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6TC0-41SBGDH-1&_user=37161&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_acct=C000004218&_version=1&_urlVersion=0&_userid=37161&md5=4db60dc9352996fc4865b9d781b0128d

'''Article 2'''

'''Developmental stages in the rabbit embryo: guidelines to choose an appropriate experimental model''' --[[User:Z3187802|Vishnnu Shanmugam]] 21:05, 30 August 2009 (EST)

''S. Beaudoin; P. Barbet; F. Bargy''
''Fetal Diagnosis and Therapy; Nov/Dec 2003; 18, 6; Academic Research Library''
''pg. 422''

'''Summary'''

The article describes the various stages in the developing rabbit embryo and the rationale for using rabbits to study normal and abnormal embryology. The article details normal developments in the rabbit embryo and compares it to the developing human embryo. By making this comparison the article argues for the validity of rabbit embryology to better understand human embryology and also suggests that due to the similarities in the developing rabbit and human embryos, experiments on rabbit embryo’s yield more reliable results for human embryology. The article has some rare images on normally developing rabbits and breaks the developmental stages down (in days) describing the observable characteristics that form (eg. Limb development & body formation).
I have decided to use the image provided in the journal.

Definitely worth reading people, follow the link!

http://content.karger.com/produktedb/produkte.asp?typ=fulltext&file=FDT2003018006422

'''Article 3'''

'''Acheiropodia is caused by a genomic deletion in C7orf2, the human orthologue of the Lmbr1 gene''' --[[User:Z3187802|Vishnnu Shanmugam]] 04:32, 2 September 2009 (EST)

''P. Ianakiev, M. J. van Baren, M. J. Daly, S. P. A. Toledo, M. G. Cavalcanti, J. Correa Neto, E. Lemos Silveira, A. Freire-Maia, P. Heutink, M. W. Kilpatrick, P. Tsipouras''
''Am. J. Hum. Genet. 68:38–45, 2001''
''Department of Pediatrics, University of Connecticut Health Center, Farmington, CT;''
''Department of Clinical Genetics, Erasmus University, Rotterdam;''
''Whitehead Institute for Biomedical Research, Cambridge, MA;''
''LIM/25-D, University of Sao Paulo School of Medicine,''
''And Private Practice, Sao Paulo;''
''Private Practice, Porto Alegre, Brazil;''
''Department of Genetics, UNESP-Universidade Estadual Paulista, Botucatu SP, Brazil''

'''Summary'''

The article describes the developmental abnormality Acheiropodia can be passed down genetically from parent to offspring. Acheiropodia (also known as Horn Kolb Syndrome) is a condition where the distal extremities of the embryo fail to form. Although it is not fatal, the individual endures a very difficult life without hands and feet. The article notes that the disorder only affects the development of the limbs and has no other reported manifestations. The article defines this to be an autosomal recessive disorder which means that two copies of an abnormal gene must be present in the affected individual in order for the disease to develop. Thus, each parent passes an abnormal gene to the offspring. It is interesting to note the process of the malformation from genotype to phenotype: small deletions on the chromosomes produce abnormal genes, the abnormal genes are then passed down to the offspring, the offspring that inherits two of the abnormal genes is unable to code for the correct proteins and as a result, there is failure in normal development of limb extremities in the embryo phenotype. The article also has a shocking image of an individual with Acheiropodia which highlights the extent to which it can impact a person’s life and the urgent need to find a cure.

Read more about the exact nature of the abnormal gene using the link.

http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=1109034

'''Article 4'''

'''Epidemiology of congenital clefts of the lip and palate''' --[[User:Z3187802|Vishnnu Shanmugam]] 04:32, 2 September 2009 (EST)

''JOHN C. GREENE'' ''D.M.D. ,M.P.H.'' ''Public Health Rep. 1963 July; 78(7): 589–602''

'''Summary'''

This review article combines research to study the factors causing the developmental abnormalities cleft palate and cleft lip in populations. “Cleft palate (palatoschisis)” and “cleft lip (cheiloschisis)” are the terms used to describe the non- fusion of the upper lip, hard or soft palate and typically occur during the gestation phase of embryonic development. The article tables the occurrence of cleft palate and cleft lip in populations of people in various cities across the world. It also compares the occurrence of cleft palate and cleft lip in males and females. The article finds that the incidence of cleft palate and cleft lip is:

*Is random in males and females (ie. Occurs approximately evenly in both sexes)

*Is random in people living in different cities

*Is higher in children of mothers over the age of 35

*Is higher in white populations and lower in the negro populations which suggests possible role of environmental factors

*No concrete proof that cleft palate and cleft lip is hereditary

*Is higher in rats exposed to radiation and those fed riboflavin

*Is higher in rabbits and other lab animals exposed to higher stress through cortisone injections

Although the article is now quite ancient, it is interesting to note the incidence of cleft palate and cleft lip among people. It also shows the historical foundation of research into the causes of cleft palate and cleft lip through animal experimentation.

Read more about cleft palate epidemiology using the link.

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1915191

'''Article 5'''

'''Chromosome abnormalities in human embryos''' --[[User:Z3187802|Vishnnu Shanmugam]] 00:10, 13 September 2009 (EST)

''Santiago Munne & Jaques Cohen The Center for Reproductive Medicine and science of Saint Barnabas Medical Center, New Jersey, USA Human Reproductive Update 1998, Vol. 4, No. 6 pp. 842-855 European Society of Human Reproduction and Embryology''

'''Summary'''

As the title suggests, this article focuses on chromosomal abnormalities in the developing human embryo. To understand this article, it is necessary to first establish some basic definitions that are used throughout the article. Aneuploidy can be defined as the occurrence of one or more extra or missing chromosomes leading to an unbalanced chromosome number. Although most babies with an unbalanced amount of chromosomal material miscarry during the first trimester of pregnancy, those that are born have crippling conditions such as:

* Birth defects

* Turner's syndrome (disorder where a female child is born with only 1 X chromosome)

* Down's syndrome (disorder where child is born with 3 copies of chromosome 21)

* Edward's syndrome (disorder where child is born with 3 copies of chromosome 18)

* Patau's syndrome (disorder where child is born with 3 copies of chromosome 13)

* Klinefelter's syndrome (disorder where male child is born with 2 copies of the X chromosome and 1 Y chromosome)

Polyploidy is a type of aneuploidy where the baby has three, four, or more sets of chromosomes instead of the two present in diploids. Chromosomal mosaicism is when different cells within an individual, who has developed from a single fertilized egg, have a different chromosomal makeup. Most commonly there will be some cells with a typical number of chromosomes (46 chromosomes) and other cells with an altered number or structure of chromosomes.

The article explores the possible causes of chromosomal abnormalities resulting from pregnancy though techniques such as IVF (In-Vitro Fertilization) and ICSI (Intracytoplasmic Sperm Injection). It also analyses the role of FSH (follicle stimulation hormone), temperature, water and light in chromosomal abnormalities.

The article finds:

* High FSH concentration increases likelihood of chromosomal abnormalities

* ICSI & IVF techniques have increased likelihood of chromosomal abnormalities

* Chromosomes exhibit temperature sensitivity and changes in temperature can cause chromosomal abnormalities

Although the article makes a number of findings, it is yet to be backed up with convincing evidence; the article has some really cool images of the developing embryo soon after fertilization. Overall, an interesting read.

Interested? Follow the link!

http://humupd.oxfordjournals.org/cgi/reprint/4/6/842.pdf

'''Article 6'''

'''Evaluation of the Safety and Pharmacokinetics of the Multi-Targeted Receptor Tyrosine Kinase Inhibitor Sunitinib During Embryo–Fetal Development in Rats and Rabbits''' --[[User:Z3187802|Vishnnu Shanmugam]] 00:10, 13 September 2009 (EST)

''S. Patyna, J. Haznedar, D. Morris, K. Freshwater, G. Peng, J. Sukbuntherng, G. Chmielewski, and D. Matsumoto''
''Pfizer Global Research and Development, San Diego, California''
''Roche LLC, Palo Alto, California''
''Pfizer Global Research and Development, Kalamazoo, Michigan''
''Xenoport Inc., Santa Clara, California''
''Pfizer Global Research and Development,'' ''Groton, Connecticut '' ''Birth Defects Research (Part B) 86:204–213 (2009)''

'''Summary'''

The article looks at how toxicity affects embryo-fetal development. The article describes the abnormal changes that occur when Sunitinib (an oral inhibitor of multiple receptor tyrosine kinases) is administered to pregnant rabbits and rats. This experiment was performed in an attempt to mirror the effects of antiangiogenic agents used in cancer treatment. Sunitinib is an antiangiogenic agent and the use of antiangiogenic agents is not recommended for treating cancer in pregnant patients because of the potential harm to embryo-fetal development. Angiogenesis (the formation of blood vessels) plays a critical role in embryo–fetal development and antiangiogenic agents slow down and/or stop the formation of blood vessels in order to control cancer and stop its spread. In pregnant patients however, this has the potential to adversely affect the developing embryo and these adverse effects is what is investigated in this article.

The article finds the antiangiogenic agent Sunitinib at toxic levels can result in:

* Embryo death

* Fetal skeletal malformations including vertebrae malformation and cleft lip/palate

* Teratogenic effects in rabbits

* Decreased maternal and fetal body weight

This article is a recent study and provides important findings regarding the use of antiangiogenic agents, especially during pregnancy. Although the maternal effects are minimal, the adverse effects to the embryo are significant and permanent. The article makes good use of tables and graphs to juxtapose pieces of information and to show trends. It is very interesting to note the extent to which chemicals can impact the vulnerable developing embryo.

Read more at link. (Use institutional login from UNSW computers)

http://www3.interscience.wiley.com/journal/122262246/abstract?CRETRY=1&SRETRY=0

------
thank you so much Vishnuu~~^^ from Juliana
-----
I also changed the format if you guys dont mind--[[User:Z3126328|Jin Lee]] 18:33, 31 August 2009 (EST)
----

Hey '''Vishnuu''', that link you found with the stages is awesome! thanks so much. Do you know if i am allowed to use the embryo pics in that article on our wiki page?? i'm not sure about the copyright rules. It says at the bottom of the article "Reproduced with permission of the copyright owner. Further reproduction prohibited without permission."
Does this mean we can only provide a link to it on our page? if so that's a shame, because those pics were fantastic!! '''SUM'''

Oh i also added an introduction - sum

Hey Sum,
Unfortunately, since its copyright protected we can't use the image directly......but there is a way of getting around it....You can modify the image using picture editing tools, then simply reference where the original picture came from and state that it has been modified by you. Alternatively, you can trace around the picture and provide only an outline (this will be very difficult to do with detailed pictures, a good picture editing software is recommended). Either way according to whats written under '''editing basics''' we need to include a picture that has been drawn up ourselves in the project. Also, not sure if you are aware, but the project is NOT due on Thursday (3rd September), Dr. Hill has very generously given everyone an extension till after mid-session break. --[[User:Z3187802|Vishnnu Shanmugam]] 02:35, 2 September 2009 (EST)

==Julianna's Research==
[http://netvet.wustl.edu/species/rabbits/rabtmodl.txt]
HISTORY OF THE RABBIT (IN RESEARCH)

A. Discovered in Spain about 100 B.C.
B. Domesticated in the 1500's
C. Standardization of breeds in 1800's
1. Research Uses
a. 1852: Rabbits have DL-hyoscyamine
(a) Can survive belladonna
(b) Endogenous atropine esterase
b. 1884: Pasteur develops rabies vaccine
c. 1891: Heape performs embryo transfer
(a) Influence on phenotype of the
uterine environment
d. 1908: Ignatowsky produces atherosclerosis
(a) Fed diets of milk, meat, and
eggs
(b) Produced intimal lesions
(c) Believed lesions due to protein
e. 1928: Demonstrated intranuclear development
of herpes virus
f. Graafian follicle was first observed
g. Coat colors and Mendelian inheritance
h. Immunology studies
i. Testing of human use products
j. Basic science studies
k. Diagnostic requirements
l. Eye Research
m. Pyrogen testing
n. Fetal drug induced teratology
o. Parasite research

LITERATURE REVIEW OF RABBIT USE

A. 1956 to 1800 ... Over 8000 citations
B. 1966 to 1987 ... 130,000 citations linking the rabbit to
all areas of research
C. 1988 to present ... 821 citations under the search
criteria: Rabbit: Model: Human Disease
D. Numbers of Rabbits Used (APHIS; ILAR records 1989)

1967 504,500
1978 439,986
1982 547,312
1983 466,810
1984 529,101
1985 544,621
1986 521,773
1987 534,385

ADVANTAGES OF USING RABBITS
A. Provides repeatability of animal model studies
B. Large enough for single samples
C. Many stocks/strains as animal models
D. Easily managed
E. Quality of immunologic products
F. Ease of reproductive control

DISADVANTAGES OF USING RABBITS
A. Most colonies are a storehouse of diseases
B. Extremely variable to responses to general anesthetics

[http://www.ncbi.nlm.nih.gov/pubmed/18430597]
The rabbit as a model to study asthma and other lung diseases.Keir S, Page C.
Sackler Institute of Pulmonary Pharmacology, Division of Pharmaceutical Sciences, 5th Floor Hodgkin Building, King's College London, Guy's Campus, London SE1 9RT, UK.

No single animal model is able to reproduce all the features of human asthma. However, the similarities between neonatally immunised rabbits and human asthma highlight the value of this model in the investigation of asthma pathophysiology and in the development of therapeutic agents. Airway inflammation and airway responses to various stimuli including histamine, adenosine 5'monophosphte and antigen in allergic rabbits have shown similarities with the responses observed in asthmatics. Furthermore, functional studies in rabbit airways show they are poorly responsive to capsaicin as are human airways. Chronic pre-treatment with capsaicin desensitises the TRPV(1) receptor enabling studies into the effect of this drug in both rabbits and man. The allergic rabbit model has been used extensively in assessing the various classes of anti-asthma drugs and is sensitive to similar drugs as patients with asthma, including beta-adrenoceptor agonists, corticosteroids, phosphodiesterase inhibitors and theophylline. This article highlights the usefulness of the rabbit as a species to study lung biology.

[http://www.ncbi.nlm.nih.gov/pubmed/8447943]
Effects of strain and embryo transfer model (embryos from one versus two donor does/recipient) on results of cryopreservation in rabbit.Vicente JS, García-Ximénez F.
Departamento de Ciencia Animal, Universidad Politécnica de Valencia, Spain.

Differential effects of 2 transfer models for normal thawed embryos of 1 donor doe were studied on the offspring rate and their embryo survival at birth from 3 selected rabbit strains (SY and SB: synthetic strains, NZ: New Zealand White). Morulae were obtained 64-66 h post-coitum from 93 adult does treated with 25 IU of hCG (SY:36, NZ:27, SB:30). Morphologically normal morulae were frozen in the presence of 1.5M DMSO and stored in liquid nitrogen. Normal thawed embryos were transferred into the oviducts of synchronized recipient does of the same strain 48 h after being injected with 25 IU of hCG (SY:28, NZ:21, SB:24). Each recipient received embryos from 1 (single transfer) or 2 different donor does (double transfer). Significant differences were observed in the post-thawing percentage of normal embryos between strains (SY:95 +/- 1% and SB:85 +/- 3%, P < 0.05; NZ: ,91 +/- 2%). After transfer, no significant differences were observed in pregnancy rate and offspring rate between the transfer models, whereas significant differences were only found in survival rate when all transfers were analyzed (double: 24 +/- 4% vs single: 14 +/- 3%, P < 0.05). An effect of strain was detected in the pregnancy rate (NZ: 33% vs SB: 71%, P < 0.05; SY: 61%) and in the survival rate per donor doe on pregnant recipient doe (SY: 42 +/- 5 vs SB: 19 +/- 5, P < 0.05; NZ: 34 +/- 7%). These results suggest a differential embryo sensitivity with respect to their genetic origin in both the freezing-thawing and transfer procedures.

--[[User:Z3126328|Jin Lee]] 13:06, 3 September 2009 (EST)

[http://www.ncbi.nlm.nih.gov/pubmed/14064965?log$=activity]GROSS EFFECTS ON RABBIT EMBRYOS AND MEMBRANES OF X-IRRADIATION IN THE BLASTOCYST STAGE.

[http://www.ncbi.nlm.nih.gov/pubmed/11139224?ordinalpos=408&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum]Onset of zygotic transcription and maternal transcript legacy in the rabbit embryo.Brunet-Simon A, Henrion G, Renard JP, Duranthon V.
Laboratoire de Biologie du Développement, INRA, Jouy en Josas Cedex, France.

Onset of zygotic transcription is progressive from the one-cell stage onward in the rabbit embryo. Maternal transcripts remain fairly stable until the 8-16 cell stage when major transcriptional activation of the zygotic genome takes place. To understand the mechanisms of the maternal-to-zygotic transition in the genetic information governing development, we asked whether a progressive synthesis of zygotic transcripts takes over the maternal molecules, or whether the synthesis of zygotic transcripts is very abrupt and independent of the persistence of the maternal counterparts. To answer this question, we set up mRNA differential display experiments comparing the mRNA content of rabbit embryos at different stages during the preimplantation period. We isolated eight zygotic transcripts whose synthesis is abruptly turned on at the 8-16 cell stage. These transcripts are involved in general cellular metabolism and their maternal counterparts are still present up to the four-cell and even the 8-16 cell stage. This identification of early zygotic transcripts suggests that global long range modifications of chromatin structure result in a rapid increase in transcription rates during the major transcriptional activation of the zygotic genome.

[http://www.ncbi.nlm.nih.gov/pubmed/11245264?ordinalpos=409&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum]
Reconstruction of the heteroparental diploid condition in rabbit zygotes by nuclear transfer.Escribá MJ, García-Ximénez F.
Departamento de Ciencia Animal Universidad Politécnica de Valencia, Spain. mescriba@dca.upv.es

Studies on genomic imprinting showed that parental genomes have complementary roles during embryogenesis, are both essential and need to be synchronized in their embryonic stage for successful development to term. To our knowledge, these studies have not been performed in species other than mice. We studied the in vitro and in vivo development of reconstructed zygotes by combining female haploid nuclear donors and androgenetic hemizygous recipients. Haploid donor embryos at the 8- or 32-cell stage were obtained from electroactivated young rabbit ova (eight pulses maximum, consisting of 0 6 kVcm(-1) for 60 microsec each, 38 min apart) which were further cultured for 24 h or 32 h. Couplets formed by both the haploid male hemizygous recipients and haploid female donor cells were electrofused (2.2 kVcm(-1) for 60 microsec duration each, 30 min apart) and their nuclear configuration determined 122 of those fused (43%: 122/286) were diploid. Reconstructed diploid zygotes developed in vitro up to the compacted morula, blastocyst and hatched stages (1/8-nuclei x 50%, 18% and 9% vs. 1/32-nuclei: 47%, 25% and 19%; P > 0.05), respectively. In embryo transfer assays, both 1/32-reconstructed zygotes and control, non-manipulated zygotes were transferred to synchronized does Four live reconstructed fetuses (4/49: 8 1% survival rate) and five in regression stage (9/49: 18% implantation rate) were observed on Day 21 post-ovulation, whereas from control zygotes, 11 fetuses were alive (11/53 21% fetal survival rate) and 2 degenerated (13/53 x 24 5% implantation rate). Similar results were obtained from a final experiment, in which development was allowed to progress to term. Six live rabbit pups derived front experimentally reconstructed zygotes (11%; 6/54) and three fetuses in regression stage were obtained; values slightly lower than those derived from non-manipulated and transferred control zygotes (18% 9/50, live born rate).

[http://www.ncbi.nlm.nih.gov/pubmed/11589623?ordinalpos=412&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum]
Effects of leukaemia inhibitory factor on endometrial receptivity and its hormonal regulation in rabbits.Liu CQ, Yuan Y, Wang ZX.
Shanghai Institute of Planned Parenthood Research, Shanghai, P. R. China.

The effects of hormones on production of leukaemia inhibitory factor (LIF) and the uterine receptivity in rabbits were studied. In ovariectomised rabbits, LIF protein was not detected in control but upregulated by progesterone alone. Oestrogen had a slightly negative effect when the rabbits were treated with both oestrogen and progesterone. Mifepristone (Mi) inhibited the progesterone-stimulated production of LIF in rabbit uterus. The transfer of embryos to LIF-treated recipients significantly increased pregnancy rate (70%) and implantation rate (27%) as compared with control (pregnancy rate=40% and implantation rate=17%). The transfer of embryos to LIF and mifepristone-treated recipients significantly decreased pregnancy rate (30%) and implantation rate (9%). The results indicated that LIF protein had a beneficial effect on uterine receptivity and mifepristone prevented this effect. Copyright 2001 Academic Press.

[http://www.ncbi.nlm.nih.gov/pubmed/8447943]
Effects of strain and embryo transfer model (embryos from one versus two donor does/recipient) on results of cryopreservation in rabbit.Vicente JS, García-Ximénez F.
Departamento de Ciencia Animal, Universidad Politécnica de Valencia, Spain.

Differential effects of 2 transfer models for normal thawed embryos of 1 donor doe were studied on the offspring rate and their embryo survival at birth from 3 selected rabbit strains (SY and SB: synthetic strains, NZ: New Zealand White). Morulae were obtained 64-66 h post-coitum from 93 adult does treated with 25 IU of hCG (SY:36, NZ:27, SB:30). Morphologically normal morulae were frozen in the presence of 1.5M DMSO and stored in liquid nitrogen. Normal thawed embryos were transferred into the oviducts of synchronized recipient does of the same strain 48 h after being injected with 25 IU of hCG (SY:28, NZ:21, SB:24). Each recipient received embryos from 1 (single transfer) or 2 different donor does (double transfer). Significant differences were observed in the post-thawing percentage of normal embryos between strains (SY:95 +/- 1% and SB:85 +/- 3%, P < 0.05; NZ: ,91 +/- 2%). After transfer, no significant differences were observed in pregnancy rate and offspring rate between the transfer models, whereas significant differences were only found in survival rate when all transfers were analyzed (double: 24 +/- 4% vs single: 14 +/- 3%, P < 0.05). An effect of strain was detected in the pregnancy rate (NZ: 33% vs SB: 71%, P < 0.05; SY: 61%) and in the survival rate per donor doe on pregnant recipient doe (SY: 42 +/- 5 vs SB: 19 +/- 5, P < 0.05; NZ: 34 +/- 7%). These results suggest a differential embryo sensitivity with respect to their genetic origin in both the freezing-thawing and transfer procedures.

[http://www.ncbi.nlm.nih.gov/pubmed/14564113]
'''Developmental stages in the rabbit embryo: guidelines to choose an appropriate experimental model.'''Beaudoin S, Barbet P, Bargy F.
Department of Pediatric Surgery, Groupe Hospitalier Cochin-Saint-Vincent de Paul, Paris, France. sylvie.beaudoine@svp.ap-hop-paris.fr

Researchers involved in the field of congenital malformations are often forced to work on an animal model. Both accurate description of its normal development and comparative staging with human development will be mandatory. To complete the lacking medical literature, we herein provide such data for the rabbit model. Sampled rabbit embryos were staged using the Carnegie criteria, in order first to determine if they were consistent with the rabbit developmental pattern, and second to compare this pattern with the human one. Our results show a suitable comparison of rabbits and humans in early developmental stages, except for the neural growth. Copyright 2003 S. Karger AG, Basel

Talk:2009 Group Project 1

2009-10-14T11:52:16Z

Z3185685: /* Actual Changes Made */

== Lab 10 ==
--[[User:Z3283499|Antonio Lee]] 10:52, 2 October 2009 (EST) Hi everyone, I will be working with you during the Lab10 Tutorial and here is the news link and PDF of the manuscript for your group exercise. I encourage you to read the paper before the tutorial. Also, please indicate next to the questions below (using either your initials or student number) which one of the four questions you wish to address.
:'''Group 1 :''' [http://www.nature.com/nature/journal/v461/n7262/full/461354a.html '''Developmental biology: Asexual healing'''] in Nature News and Views - Nature 461, 354-355 (17 September 2009) [[Media:ANAT2341_Lab10_2009_Group 1 Reading.pdf|Manuscript (PDF): Mitochondrial gene replacement in primate offspring and embryonic stem cells]]

:Question 1. What is the background to the existing problem / disease condition? --[[User:Z3187802|Vishnnu Shanmugam]] 22:12, 2 October 2009 (EST)

Mitochondria are found in all eukaryotic cells and contain their own genome (mitochondrial DNA or mtDNA). Unlike the nuclear genome, which is derived from both the egg and sperm at fertilization, the mtDNA in the embryo is derived almost exclusively from the egg; it is of maternal origin.

Mutations in mitochondrial DNA (mtDNA) can lead to a range of chronic incurable diseases such as myopathies, neurodegenerative diseases, diabetes, cancer and infertility. Mutations in mitochondrial DNA could also contribute to other diseases such as Alzheimer’s,
Parkinson’s and Huntington’s diseases

A normal cell should be homoplasmic in its mitochondrial DNA, that is it should only contain one type of mitochondrial DNA. But if the cell has two or more types of mitochondrial DNA (a mixture of normal and mutated DNA) it is known as heteroplasmic and can lead to a range of diseases. These genetic mutations can also be passed to offspring causing disease.
1 in 3,500–6,000 are at risk or presently have a disorder from mutations in mitochondrial DNA. Disease progresses slowly and there are no cure. Limitations in assessing the extent heteroplasmy and accuracy in calculating the risks of developing mtDNA related disease means that a new approach is needed to tackle the problem.

:Question 2. What approach / method did the research team take to tackle / improve the problem?--[[User:Z3126328|Jin Lee]] 12:31, 7 October 2009 (EST)
:Working with rhesus macaque monkeys, the authors reconstructed mature oocytes containing the nuclear genome from one oocyte and the mitochondrial genome from another. To do this they removed the nuclear genetic material from one oocyte, leaving behind all of the mitochondrial DNA, then transferred it to another oocyte whose nucleus had been removed (a cytoplast), but which contained a full complement of mitochondrial DNA.

:Question 3. What was the breakthrough / major advancement OR failure / drawback? and why might this be of significance?
::Drawbacks - --[[User:Z3186093|Jenny Guy]] 22:43, 7 October 2009 (EST)
:::There were difficulties in visualising and isolating the intact chromosomes, as well as the mtDNA being susceptible to damage and translocation/movement. Visualization became easier after the development of techniques for DNA staining with fluorophores and looking under UV light during embryo cloning by the SCNT (somatic cell nuclear transfer). Successful implementation to avoid damage to the cytoplast during spindle removal involved using polarized microscopy. (p368) --[[User:Z3186093|Jenny Guy]] 14:12, 8 October 2009 (EST)
:Question 4. What are the next steps in moving forward? What are the next or new hurdles to overcome?

==Actual Changes Made==

'''Concise Version:''' (Everyone add their changes here)
# Removed cleft palate and cleft lip section (Abnormal development) --[[User:Z3187802|Vishnnu Shanmugam]]
# Altered references (current research and abnormal development) --[[User:Z3187802|Vishnnu Shanmugam]]
# Added picture guide for transgenic rabbit --[[User:Z3187802|Vishnnu Shanmugam]]
# Added picture guide for rabbit cloning --[[User:Z3187802|Vishnnu Shanmugam]]
# Removed newspaper image of rabbit (Current research) --[[User:Z3187802|Vishnnu Shanmugam]]
# Formatted pictures and text to reduce gaps in the assignment (current research and abnormal development) --[[User:Z3187802|Vishnnu Shanmugam]]
# Corrected spelling mistakes in images (current research and abnormal development) --[[User:Z3187802|Vishnnu Shanmugam]]
# Reviewed all images and have written a summary, original source, copyright information (current research and abnormal development) --[[User:Z3187802|Vishnnu Shanmugam]]
# Formatted the look of the genetics section, including 'abnormalities' --[[User:Z3186093|Jenny Guy]] 16:31, 14 October 2009 (EST)
# Fiddled with position of images in genetics section --[[User:Z3186093|Jenny Guy]] 16:31, 14 October 2009 (EST)
# Fixed spelling mistake in History - Jin Lee
# Added images in table of stages. --[[User:Z3185685|Sumaiya Rahman]] 22:52, 14 October 2009 (EST)

'''Long Version:'''

--[[User:Z3187802|Vishnnu Shanmugam]] 23:46, 10 October 2009 (EST) Okies, all done. I'm going to review all my images and add summaries to them. Dr. Hill asked for a concise version to all the changes we make from the peer review process. I suggest everyone add their changes to the list I have started above and place your signature next to it.

--[[User:Z3186093|Jenny Guy]] 14:29, 10 October 2009 (EST)Hey vishnuu, i was thinking could you please alter
* the gaps between the spina bifida images (format this somehow with the images on the side and text on the other)
* the gap under "Brachydactylia & Acheiropodia"...maybe you have entered down too much????
cheers :)

--[[User:Z3187802|Vishnnu Shanmugam]] 21:27, 9 October 2009 (EST)Hey all. I have removed the newspaper image of rabbit (Due to copyright issues), and have replaced it with a series of images that guides the reader through the process of cloning a rabbit. I have NOT altered the text summarizing the creation of transgenic and clone rabbits as there are very important & detailed information which if removed puts complex processes in danger of oversimplification. I also corrected spelling mistakes in some images.

--[[User:Z3187802|Vishnnu Shanmugam]] 20:22, 7 October 2009 (EST) Hey gang. By popular demand (or the stress of reading) people want less text. I have removed the entire cleft palate & cleft lip section from abnormal development. For current research, I have also created a step by step picture guide for transgenic rabbit creation. It was initially meant to be a video, but this wiki page does not display (.gif) or (.mov) files. Sum, I remember that you did your references after me...so when I removed the cleft palate & cleft lip section, the references changed....so I have also adjusted your references accordingly. I don't think it is necessary to make all the changes outlined below as most comments are subjective (different people have different preferences) and seems like some comments were made because people had nothing else to propose.

--[[User:Z3126328|Jin Lee]] 10:01, 8 October 2009 (EST)Hi Guys, I have fixed spelling mistake and some people commented to make table form for advantages and disvantages section. But I liked the way I presented so I will leave in point form.

--[[User:Z3186093|Jenny Guy]] 14:32, 8 October 2009 (EST)
Hey! I looked at what i could change in the genetics section and decided to format a little. Our peers asked:
* genome information into a table - this is a little silly since there'd only be one column.
* Reformating in sections such as hitory and genetics. - have tried to do a little.
* Make pictures appear on the same side of page. maybe aligning the pics on either the left or right side instead of both left and right, and possibly putting them as thumbnails could also work. - i tried to put both of the chromosome images ont he same side (tried both left and right) but found that it looked terrible considering the size (which is needed to see it) as the text wouldnt fit around it very well.
* it will look much better if there is some work to be done for the structure of it especially the paragraph under the heading of 'abnormalities'. - am still in the process. not sure what else i can do since its in basic dot point form with not a large text to format. any ideas? or shall i leave it how it is now?
* maybe instead of writing the entire reference, you could just state The Broad Institute or just the people related to it - i feel that the entire team needs a mention since all people relate to it. noting just the broad institute is almost like noting a team of people here in unsw as just plainly "UNSW" which is just disrespectful.

==Things to work on noted by peers==

Hey, So the changes i will make will be in the introduction section. Also a lot of people have said to add pictures in the stages section to make it more interesting. I couldnt get permission to use the images so i bought tracing paper today! lol will try to draw them and see if they are ok enough to add. I think i am going to leave the timeline section as is because most people liked it. What do u guys think? --[[User:Z3185685|Sumaiya Rahman]] 15:31, 8 October 2009 (EST)

Sounds great Sum....Its gonna take some effort to trace it then scan it. GL --[[User:Z3187802|Vishnnu Shanmugam]] 21:37, 9 October 2009 (EST)

Hey guys,
I read through all the notes our peers have given us and summarised them into the following sections. Majority of them overlap (where ive put a new persons opinions in the same dot point over and over to stress the point on how many people noticed). Some things are easily changed, most of all i reckon its
# formatting
# pictures
# text to be more concise
So we just need to finalise all these minor things to improve our project. Please detail any changes you've made in the the heading above.
Cheers, --[[User:Z3186093|Jenny Guy]] 20:30, 7 October 2009 (EST)

INTRODUCTION
* a little too brief, more information needed
* For the first sentence (the characteristics that make the rabbit an excellent model for study), mention the section 'Why are we using rabbits?' under History section.
* For the second sentence (study that developed and improved micromanipulation techniques), mention the 'Transgenic Rabbit' section below under the genetics section. I've read the entire project page, and the introduction was the only place I found that was not precise enough (which is a great thing). These are minor things, but I think they will help with improving your project page.
*suggestion: Place the history section after the Introduction. This gives the viewer an overview of the use of the rabbit embryo. This way the viewer is first subjected to a few examples of the rabbit embryos use. It also allows him/her to understand where the rabbit embryo sits in with history. I guess this is a matter of personal preference.

HISTORY
* The advantages and Disadvantages would be better in a table. the history you might want to put the advantages and disadvantages into a table to make the page look a bit more tidy and easier to read when we go through it.
* The usage of rabbits for experimental models in science and medicine could be stated under the history section to allow background information for the readers to become aware of the topic and why the rabbit have been used to study specfic medical procedures and diseases.
* Spelling mistake under 'Discovery of Graafian Follicle', 2nd paragraph. I think it's previous instead of 'previcous'.
* Reformating in sections such as hitory and genetics. Make pictures appear on the same side of page.
* The history section can be improved if the infomation is expanded to give some more detailed background knowledge although i like the idea that the information is concise describing each scientists contribution towards the model.
* could be formatted to make the information stand out and a lot more appealing, I would recommend including pictures if possible that link to the text and making the advantages and disadvantages into a table rather than listing it.

TIMELINE
* more images to wholly understand. timeline/staging section was clear and concise, however it could be improved by adding more colour/pictures to maintain the readers' interest. The timeline and staging bits are very well written and clear but i think you should add a few images in there to match up with the text. Perhaps some pictures of embryos throughout development. Pictures for every stage would make it more visually attractive rather than just reading text. lack of pics in the timeline.
* It’s a little confusing that the development jumps back and forth according to the body part developing. Maybe it should be categorised according to time of development instead for greater clarity at first glance
* The timeline is just a little confusing, as its divided into development of different parts, which breaks the time flow.
* some of the information for the timeline section was too heavy for the page - would recommend only using some of the information on your actual page and having the rest as links to separate pages

STAGING
* pictures for stages would have been nice, unless there were none????
* a more even distribution of information, particularly more detail in the stages
* Provide pictures for individual stages. Get visual, and make the stages interesting to read. include pictures in the stages section.
* Staging section is also very well presented but the information presented in a table would even look better if there is use of some pictures to make it more interesting for its audience.
* staging section was very bland and would be more appealing with pictures. I dont think its necessary to cite your entire reference within the text

GENETICS
* genome information into a table
* Reformating in sections such as hitory and genetics.
* Make pictures appear on the same side of page. maybe aligning the pics on either the left or right side instead of both left and right, and possibly putting them as thumbnails could also work.
* it will look much better if there is some work to be done for the structure of it especially the paragraph under the heading of 'abnormalities'.
* maybe instead of writing the entire reference, you could just state The Broad Institute or just the people related to it

ABNORMAL DEVELOPMENT
* There is also a lot of content which might be alleviated by reducing the section on abnormal development. Too much information about the abnormalities. make more concise.
* the abnormalities went a bit over board, and didn't need that much attention I think (as compared witht the research which was good)
* reduce the writing content. for example. In the current research section, you have two scientific process of transgenic rabbits as well as cloning which is described in how these are done. why not draw a step by step diagram, and put these written steps in the link to the image.
* The information provided under Hydrocephalus and Brachydactylia was informative and interesting, but it contained too much text. I suggest you narrow it down and make use of Dots point, numbering, bold/italic words, and/or sub-sub-headings.
* Section for "Abnormal Development" gives the readers useful amount of information but i think its very lenghty, use of dot points can make it look even better and easy to understand.

CURRENT RESEARCH
* the group makes good usage of diagrams but towards the end diagrams die out, you might want to make the current research part of your assignment into diagrams and steps as there is just a bunch of information thrown there and alot of reading needed, if you put it into steps or diagrams it will make the marking process and reading process easier and allow us as reader to understand the information with ease.
* 'Transgenic Rabbit' should be shifted toward the genetic information on the rabbit. (Jenny - i dont agree with this as its research, not its offical genetics. Vishnnu - Neither do I)
* information in regard to stem cells should be brief and truncated. Example in regard to stem cell research should have brief and simple model explaining the process and why it used.
* There is too much information under stem cells. There is 2 examples of studies dealing with stem cells. A suggestion would be to just have one, and have a link saying 'Koga's research on Stem Cells'.
* Have the section 'links to Research labs and researchers' placed at the end of current research. That way, the information on the page will flow smoother.
* more of a focus on current research i.e. what each method is being used for and less on the process behind each method.
* great amount of information but in my perspective replacing the paragraphs with some dot points with heading and subheadings would further enrich understanding of readers.

OVERALL
* "As you start going down the page though the information starts to read a bit haphazardly, for example the developing body; jumping for section to section and the timeline section. it would be great if you could clean this up as it doesn't really flow." - formatting
* condense long slabs of text as the page is long
* format it so there are no huge gaps
* move the links to current research labs up closer to the current research section, just to keep it all together

==Constructive Criticism of Coordinator==
--[[User:S8600021|Mark Hill]] 08:07, 8 October 2009 (EST) The following comments are general in nature in no specific order, as it would be inappropriate to suggest specific changes and then assess the final project. Comments will be added during this week and you still have one week before final submission.

* There is no concise list of changes made to your project on the basis of peer assessments.
* Timeline of Embryo Development early stages, are in the introductory text said to be in hours, but it would be good to see it in the list as well.
* [[:File:Sizes.JPG]] Relative sizes, but no absolute size or scale given.
* A general comment about images. When you click an image and it opens, the information below the image should have an explanation of what the image shows, a reference (if from a paper) and a link to the original source (if available) as well as copyright information.
* Did you actually read the terms of use for this image that you cut n pated into the image description? [[:File:Rabbit_hybrid.jpg]] "For this purpose alone you may retrieve and display the Content on a computer screen. You may also print out, but not photocopy, one copy of individual files on paper and store files in electronic form on disc, but not on any server or any other storage device connected to a network where the Content could be accessed by other users." It clearly states that you cannot use this image online.
* Chromosomes section, images have no legends and structure not clearly organised.
* There needs to be better checking of your spelling and grammar, for example [[:File:Rabbitmalformation3.jpg]] "Plant Patkology of Tke Rockefeller Institute for Medical Researck", these mistakes while not major, suggests a lack of reviewing of your work by the group.
* Just a comment on project "feel", when several people work together on a project and insert their parts, the final project sometimes has an uneven style. Now that you have time to tidy up, try and get a common appearance throughout your project.

==Constructive Criticism of Peers==

--[[User:Z3218657|Sally Clarke]] 09:32, 1 October 2009 (EST)
Nice work Guys!
- Fantastic images used throughout - maybe a few more in the timeline so we can understand what is going on
- As you start going down the page though the information starts to read a bit haphazardly, for example the developing body; jumping for section to section and the timeline section. it would be great if you could clean this up as it doesn't really flow.
- The section on the abnormal development is great.
- The page is quite long - Maybe you could condense some of the text as it is kind of slab like
- i really enjoyed the breeding section
- The advantages and Disadvantages would be better in a table.

--[[User:Z3223194|Bronwyn Lewis-Jones]] 08:08, 1 October 2009 (EST) Hi Group 1! This is obviously a well organised and well researched assignment. I found it very informative. There are (of course) some things I feel could improve the overall submission. I loved that the timeline/staging section was clear and concise, however I think it could be improved by adding more colour/pictures to maintain the readers' interest. There is also a lot of content which might be alleviated by reducing the section on abnormal development. Hope this helps :)

--[[User:Z3218146|Julianna Lam]] 01:11, 1 October 2009 (EST) good job guys.
-Theres alot of relevant information.
-The timeline and staging bits are very well written and clear but i think you should add a few images in there to match up with the text.
-The image for the genetics bit is awesome.
-The page is nicely set out.
-Too much information about the abnormalities.

--[[User:Z3258567|Sando Rashed]] 20:04, 30 September 2009 (EST)hey guys, your page looks good, starts off well as there is not a bunch of information just thrown in, the information used is well thought, with the history you might want to put the advantages and disadvantages into a table to make the page look a bit more tidy and easier to read when we go through it (you can also do this with the info under genome), the group makes good usage of diagrams but towards the end diagrams die out, you might want to make the current research part of your assignment into diagrams and steps as there is just a bunch of information thrown there and alot of reading needed, if you put it into steps or diagrams it will make the marking process and reading process easier and allow us as reader to understand the information with ease, other than that the page looks quite good, well done on all your contributions

--[[User:Z3218792|Gabriela Pinget]] 21:51, 29 September 2009 (EST)

Nice page. I particularly liked the idea of lists of what is to come before each flood of information as was done with the ‘history of model use’ section.

- Nice easing into the topic with ‘advantages’ and ‘disadvantages’ lists.

- I liked the of rabbit embryo development to that of humans- puts it into perspective

- Good glossary- informative but not over- the- top

- Nice genetics section! Easy to read and a great use of illustrations to break up the information

- I also like that you took a page out of Mark’s book in the addition of the abnormalities section

Improvements:

- Perhaps some pictures of embryos throughout development.

- It’s a little confusing that the development jumps back and forth according to the body part developing. Maybe it should be categorised according to time of development instead for greater clarity at first glance

--[[User:Z3295026|Joe Nassif]] 17:01, 29 September 2009 (EST)

Your assessment has come along great in regard to the criteria format. There are a few alterations that could improve your project, the following alterations may enhance your wiki page:

'''-''' The usage of rabbits for experimental models in both science and medicine could be state under the history section to allow background information for the readers to become aware of the topic and why the rabbit have been used to study specfic medical procedures and diseases.

'''-''' Secondly the information on 'Transgenic Rabbit' should be shifted toward the genetic information on the rabbit. So far the project is looking and coming along great except for minor edits.

'''-''' Background information should be placed subsequent to the introduction allowing the reader to understand why this specific animal is used for specfic purposes.

'''-''' Figures/Graphs and the illustration of the anatomy and genetic development of the embryo were useful and clear allowing the viwers to understand and learn through the demonstration of pictures which were extremely informative.

'''-''' Genetics: the Genetics and Abnormalities information was great and very informative. It was great how the group compared the embryo with the human chromosome allowing the audience to understand the difference between both.

'''-''' Abnormalities: Information and details which were in the genetic section provided informative and interesting information, and it could be truncated a bit, additionally just discussing the chromosome development of the rabbit.

'''-''' Current Embryology Research: information in regard to stem cells should be brief and truncated. Example in regard to stem cell research should have brief and simple model explaining the process and why it used.

'''-''' Consequently, I thought the project was good it flowed and was very informative. The information was detailed, and the illustrations were useful and allowed the readers to gain a brief overview on the topic and it usage in history and in current research. Overall group 1 seem to achieve the critriea outcomes and summarised the topic really well, the comparsion to human embryo development througout the text was great and is a good referencing point in comparsion to the species choosen.
Great job --[[User:Z3295026|Joe Nassif]] 17:01, 29 September 2009 (EST)

--[[User:Z3255007|Sadaf Masood]] 12:09, 30 September 2009 (EST)Hello Group 1! Congrats on your awesome group project! I must say im very impressed with all the information you have posted and i have listed down the good bits and the bits that need to be improved. Since i am posting this a lil late, i have seen that u have already improved your project and few aspects...Good Job guys!

1. Very brief introduction...maybe just a little bit more info will be perfect

2. Abnormalities section is very informative and well researched, but very long, how about making it a little more precise?

3. The Advantages and Disadvantages of the using Rabbit is just simply perfect

4. The timeline is just a little confusing, as its divided into development of different parts, which breaks the time flow.

5. Pictures for every stage would make it more visually attractive rather than just reading text

6. Great Glossary!

There were few things earlier that need to be improved but you guys fixed it as soon as comments were posted so basically you guys rock :)An excellent effort guys. Best Wishes

# --[[User:Z3217015|Mitchell Mathieson]] 09:45, 25 September 2009 (EST)Very nice. The information was maybe a bit spread out, with heaps of gaps everywhere (formatting???), but the information was there, and relevant, and easy to read. I like how there was tonnes of information on current research, as I think that was the main aim, but the abnormalities went a bit over board, and didn't need that much attention I think. pictures for stages would have been nice, unless there were none???? The references are top notch, and the glossary is pretty amazing, and in the right place. Overall very good, I think formatting was the major downfall though, as it makes the page that much longer, and hence a little bit more difficult to read.

--[[User:Z3224449|Elide Newton]] 14:12, 26 September 2009 (EST)
HEllO GROUP 1: Well done on such a great assignemnt, looks like you have all worked very hard. Well my one point of constructive criticism would be to reduce the writing content. for example. In the current research section, you have two scientific process of transgenic rabbits as well as cloning which is described in how these are done. why not draw a step by step diagram, and put these written steps in the link to the image. that way it is more visual, the info is still there under the image link, and the page wont look as daunting to read. :) hope this helps!

--[[User:Z3254857|Begum Sonmez]] 00:46, 26 September 2009 (EST)
Hello Group 1. Firstly, I would like to let you all know that you have all done a great job. I'm impressed. I have a few suggestions that I think mite help to improve the page even more:

*Introduction:

1)For the first sentence (the characteristics that make the rabbit an excellent model for study), mention the section 'Why are we using rabbits?' under History section.

2)For the second sentence (study that developed and improved micromanipulation techniques), mention the 'Transgenic Rabbit' section below under the genetics section. I've read the entire project page, and the introduction was the only place I found that was not precise enough (which is a great thing). These are minor things, but I think they will help with improving your project page.

3)Breeding information was informative.

4) A suggestion: Place the history section after the Introduction. This gives the viewer an overview of the use of the rabbit embryo. This way the viewer is first subjected to a few examples of the rabbit embryos use. It also allows him/her to understand where the rabbit embryo sits in with history. I guess this is a matter of personal preference.

*Timeline:

1)Graphs, and the illustration of the zona pellucida and mucin coat were very clear and informative.

*Staging: I had no problems with it. The lack of information I think was a plus. It touched on the content in the Timeline section.

*History:

1) I loved the idea of the 'Disadvantages' of the rabbit embryo, it seemed unbiased. The brief timeline provided a clear and short summary.

2) Spelling mistake under 'Discovery of Graafian Follicle', 2nd paragraph. I think it's previous instead of 'previcous'. Also, the 2nd paragraph under this heading does not flow that well. Try rephrasing the 2nd sentence.

*Genetics:

The Genetics and Abnormalities section flow into eachother very well. I appreciated the comparison of the rabbit chromosome to the human chromosome.

*Abnormalities:

1) The information provided under Hydrocephalus and Brachydactylia was informative and interesting, but it contained too much text. I suggest you narrow it down and make use of Dots point, numbering, bold/italic words, and/or sub-sub-headings.

*Current Embryology Research:
1) There is too much information under stem cells. There is 2 examples of studies dealing with stem cells. A suggestion would be to just have one, and have a link saying 'Koga's research on Stem Cells'.

2) Have the section 'links to Research labs and researchers' placed at the end of current research. That way, the information on the page will flow smoother.

Overall, I thought there was a consistent structure in each section. The information was informative, and the pictures were relevant and helped me better understand the topics of discussion.

--[[User:Z3252340|Emily Wong]] 10:58, 27 September 2009 (EST) Firstly, great work. It is a well researched, structured and organised page. The content is very in depth and includes information on all of the specified areas. It is well referenced, with an extensive reference list indicating the amount of research put into the page. Some areas are more detailed than others. For example, the staging section is quite short and concise where as the Abnormal development section is extremely long considering it is not a needed topic. There is moderate use of pictures and diagrams, but more use could benefit the page as it may be able to negate some of the large slabs of text. The comparisons made between the human and the rabbit embryos are a good part of the project page. Each member of the group has contributed to the page and provided a lot of information on the section of content they were working on. What would improve this project is a more even distribution of information, particularly more detail in the stages, a few more diagrams or pictures to negate some of the text presented, more of a focus on current research i.e. what each method is being used for and less on the process behind each method.

--[[User:Z3126345|Gang Liu]] 14:26, 27 September 2009 (EST)In my opionion, this is a well constructed page. It includes major subheadings such as history, timeline, stages, genetics and current research. It is very concise and straightforward, which makes it easy to read. For example, a short introduction paragraph,"...the rabbit is an appropriate animal model as the results from many experiments are significant to that of other mammals, including humans.", explains to reader why rabbit is such a suitable model.

It also provides a logic flow. For example, in history of rabbit model use section, it has provided advangtages and disadvantages of model use. This is appropriate, as it demonstrates the significance of rabbit model use in scitific discovery. In addition, it has provided detailed background information for each discovery. This makes it interesting to read.

It is also important to compare development of embryo between rabbit and human. For example, "... the similarities of this developmental pattern in humans and rabbits, suggests that the same growth increment is required to achieve the same stage. The main difference observed between human rabbit gestational duration is due to the fetal growth phase...", this has suggested human and rabbit share many similarities. Not only this page has demonstrated detailed written information of timeline development, it also provided graphics to reinforce the concept. For example, the hand drawing of developing embryo. As well as the comparison between human embryo and rabbit embryo timeline development.

It is also interesting to learn that rabbits have 22 pairs of chromosome, whereas humans have 23 pairs of chromosome.

Sections such as abnormal development and current research have demonstrated extended research and understanding. For example, hydrocephalus, spina Bifida, stem cell research and cloning techniques. All of these have showed the in depth research in textbooks, journals and internet based literatures.

However, this page can be improved by considering the following points.

*Provide pictures for individual stages. Get visual, and make the stages interesting to read.

*Reformating in sections such as hitory and genetics. Make pictures appear on the same side of page.

*Typo: "A rabbits potential for reproduction..."

*Sections such as abnormal development and current research are too lengthy. Might consider shrink the content.

*Lack of glossary.

Overall, big thumbs up!

--[[User:Z3252231|Angama Yaquobi]] 01:12, 28 September 2009 (EST)
First of all i would like to congratulate all the team members for a great team work.
Well done guys!! The group project looks amazing, the information presented is very concise
and straight to the point which makes it very easy for the readers to grab
the important information that they need to enhance their knowledge.
I like the section of history, the information is very clear,
and i like the idea of providing some background knowledge to the readers
about the disadvantages of the use of rabbit.
The history section can be improved if the infomation is expanded
to give some more detailed background knowledge althought
i like the idea that the information is concise describing each
scientists contribution towards the model.
The section for timeline is impressive, in my perspective its a great idea to cover alot of content in a very smart way
which is by the use of subheadings to make it easy to understand for audience.
Staging section is also very well presented but the information presented
in a table would even look better if there is use of some pictures
to make it more interesting for its audience. Genetics section
is beautifully presented, all the information is there with some
amazing pictures but will look much better if there is some work to
be done for the structure of it especially the paragraph under the
heading of 'abnormalities'. Section for "Abnormal Development" gives
the readers useful amount of information but i think its very lenghty,
use of dot points can make it look even better and easy to understand.
The same for Current embryology research, great amount of information but
in my perspective replacing the paragraphs with some dot points with
heading and subheadings would further enrich understanding of readers.
Also glossary would complement the webpage. But overall,
great amount of information which shows alot of research
which has been done by all the team members. Well done guys!!

--[[User:Z3217686|Thomas Dangerfield]] 13:29, 28 September 2009 (EST) Hey guys! Good work on your assignment! Plenty of info which is good, and very well referenced. The glossary is a good idea too! I do agree with a few others about the lots of clear spaces in the formatting, and the lack of pics in the timeline though. Also under the genetics section, maybe aligning the pics on either the left or right side instead of both left and right, and possibly putting them as thumbnails could also work. In the abnormalities section, there might have been a little too much info that probably wasn't needed, but i do like the effort put in. Over all, possibly more time spent on formatting and determining which sections are more important and which sections may need to be limited. Other than those points, the whole assignment seemed very well done!

--[[User:Z3215682|Carly Mooney]] 11:32, 29 September 2009 (EST)
You assignment is visually appealing and the genetic information e.g. the number of chromosomes of a rabbit was very interesting.There are some additional sections you have added which really complement your assignment e.g the abnormalities and I really liked the advantages and disadvantages of using the rabbit model. The few suggestions I would make is to:
* include pictures in the stages section
*place the pictures throughout the text (e.g. to left or right). You did this up until abnormalities and I felt it broke the flow of the written text.
* and maybe move the links to current research labs up closer to the current research section, just to keep it all together.
Overall very impressive though.

--[[User:Z3220040|Joanne Raffel]] 15:25, 29 September 2009 (EST) Nice wikipage, the page looked interesting however I agree with some others that the formatting of the page was inconsistent. I thought the referencing was great but found it a bit confusing with the reference numbers after the paragraphs. I thought the subheadings werent distinct enough, especially in relation to the text, which made it difficult to read. The history section could be formatted to make the information stand out and a lot more appealing, I would recommend including pictures if possible that link to the text and making the advantages and disadvantages into a table rather than listing it. I especially liked the comparison between the rabbit and the human embryo, however some of the information for the timeline section was too heavy for the page, I would recommend only using some of the information on your actual page and having the rest as links to separate pages. The staging section was very bland and would be more appealing with pictures. I dont think its necessary to cite your entire reference within the text, especially in the genetics section, maybe instead of writing the entire reference, you could just state The Broad Institute or just the people related to it. The abnormalities section was a good inclusion however it was very extensive, along with the current research section. Overall a very good wikipage.

----
*Hey, Well done guys!!! I think our group worked pretty well! I think we communicated each other well and did very best for their section. I fixed my spelling mistake and problem with sentence! As Begum mentioned, I think placing the history part after the introduction is better idea. --[[User:Z3126328|Jin Lee]] 13:36, 26 September 2009 (EST)

*Hey guys,
the project has come together brilliantly! it looks quite good. Hopefully mark will like it! ill add some terms to the glossary and try do some formatting (the first image is a little too big i think!) --[[User:Z3186093|Jenny Guy]] 10:28, 24 September 2009 (EST)

Hey. Yep all good. I had to get rid of the pics, so stages table is now blank. Im pretty much done. I'll see what i can add to the glossary. thanks :)--[[User:Z3185685|Sumaiya Rahman]] 23:34, 23 September 2009 (EST)

Hey all, I'm going to start a glossary and add it under the reference section. Scan your text and add to the glossary in alphabetical order. Also under the marking criteria, it says to provide links to researchers and research laboratories.....i'll start that under the glossary. Everyone else OK with their stuff?--[[User:Z3187802|Vishnnu Shanmugam]] 23:08, 23 September 2009 (EST)

Hey Sum, The images look fine but I don't think you can use the images like that since the journal KARGER is being particular about its copyright laws. I tried tracing around the images but it does not seem to resemble anything like an embryo. I did however find this link...go to it and scroll down to the images of the developing embryo. You might be able to edit it to resemble rabbit embryo. --[[User:Z3187802|Vishnnu Shanmugam]] 15:10, 23 September 2009 (EST). To get to the link, Google image search "rabbit gestation"....click on the "rabbit,gestation age" image from nature.com
Also google image search "The Haeckel embryo sequence"...could be useful after some editing

oh my god!! I summarised all of my research and wrote down on the page. Then I blew up everything!!!
it says 'edit conflict' what da?? I lost all of my work...it was my stupid mistake...--[[User:Z3126328|Jin Lee]] 01:06, 23 September 2009 (EST)

Oh also.. let me know if the images look stupid --[[User:Z3185685|Sumaiya Rahman]] 00:34, 23 September 2009 (EST)

Hey thanks vishnuu. I put some images up in the stages table. I did edit the pictures, but im not sure if im allowed to use it like this? have a look and let me know. Also im not sure what is going on with the reference section seems kinda all over the place, so i havnt added mine in yet. Maybe we should fix that up somehow? :) oh LOL about the breeding rabbits bit! haha
--[[User:Z3185685|Sumaiya Rahman]] 00:31, 23 September 2009 (EST)

Hey Sum, Sorry for the late reply. For $330, I'd rather breed rabbits and take the photos myself. I had a look at the original images, what we can do is trace around the developing rabbit embryo using the pencil tool on an image editing software(eg. microsoft paint - already preloaded into most windows). Then upload the image to the assignment. Does your PC have adobe fireworks?...extremely good for tracing images. If not, have a go at it with microsoft paint....I shall also have a go at it, then I shall let you know on this discussion page at about 3PM t'morrow. If any good then I'll send it to your student email. If not, we discuss potential alternatives. good luck Sum! --[[User:Z3187802|Vishnnu Shanmugam]] 23:51, 22 September 2009 (EST)

Yep thats the article i used for the developmental stages and put in a table. I should have my timeline posted by end of today. I also couldn't get permission to use the pictures as they wanted about $330 for me to use it!! no thanks. I'll see if i can work it in somehow. Vishnuu did u have any ideas on editing the images?? --[[User:Z3185685|Sumaiya Rahman]] 12:29, 22 September 2009 (EST)

Have a look at this article, it's helpful for comparison bt rabbit and human in developmental stages!--[[User:Z3126328|Jin Lee]] 13:35, 21 September 2009 (EST)
*Sampled rabbit embryos were staged using the Carnegie criteria, in order first to determine if they were consistent with the rabbit developmental pattern, and second to compare this pattern with the human one. Our results show a suitable '''comparison of rabbits and humans in early developmental stages''', except for the neural growth.
[http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowAbstract&ArtikelNr=73136&Ausgabe=229537&ProduktNr=224239
]

Absolutely correct Juliana, my research articles and their links are labelled 1-6 so far, the rest is yours..... I'll fix it for you. A timeline image seems tricky and i'm unsure, send Dr. Hill an email on m.hill@unsw.edu.au and see what he says. We still have till thursday to finish everything, so don't be too worried....try to finish all your other stuff and leave the drawing of the timeline last.--[[User:Z3187802|Vishnnu Shanmugam]] 17:49, 20 September 2009 (EST)

*no.1-7 in reference section is mine. and I think links under Vishnnu's research on the discussion board is mine. let me know please. (I can't remember all of my researches)
I want to make a timeline image but I can't do it;;; I asked Mark few weeks ago but havn't replied yet....can somebody help me???--[[User:Z3126328|Jin Lee]] 17:26, 20 September 2009 (EST)

'''** Hey Jenny, dont worry!! the project is not due until next week! (24th) we will have it done by then!! I am still waiting for permission to use the pictures in my stages section, thats why it hasnt been done yet. Hopefully i can get permission, otherwise i'll have to draw them (or something) myself.''' --[[User:Z3185685|Sumaiya Rahman]] 14:03, 17 September 2009 (EST)

It says project due date 24th september.......if the due date had been brought forward why was it not posted on the project main page? --[[User:Z3187802|Vishnnu Shanmugam]] 13:48, 17 September 2009 (EST)

EVERYONE...WHY IS THE REST OF OUR PROJECT NOT DONE??
* vishnuu...its due TODAY!! how can you post things up next Monday? Please make sure youve referenced EVERY image and all text (i know youve said you need to do this...but its easiest done when writing the section as now you have to go back and find everything, insert numbers etc. Remember to put the reference in the reference section. For the current research section i thought this might help you (as during my lecture in another class they spoke about how rabbits are used in heart development. Is there anything that you've found to include this?). Also I found this website during my research so it may help you? [http://www.evergen.com/rabbit_experience.html/ Rabbit Experiments]
* sum - where is the timeline???? It doesn't exist? Where is it? Also, we need some sort of visual for the staging. Have you found an images? Could you draw the stages of embryo development? It just looks incredibly boring.
* julianna...you need to put up more other than just two historians...there is NO referencing whatsoever in your entire section. where have you found this information? have you put it in your own words or copied it? You need to add some more refences to the reference section at the bottom..there just aren't many to back up your research.

seriously guys. ive added photos and tried to spice up the project but i am NOT going to finish your sections for you. ITS DUE IN 3 HRS! i cant believe you guys haven't bothered to even try finish this. Im very disappointed and i think its slack to let the team down. --[[User:Z3186093|Jenny Guy]] 10:34, 17 September 2009 (EST)

----

Hey all, just need to finish editing the current research part before i post it up, also need to edit some of my images under abnormal development and also references. Should be all done by Monday. --[[User:Z3187802|Vishnnu Shanmugam]] 07:02, 17 September 2009 (EST)

--[[User:S8600021|Mark Hill]] 01:40, 8 September 2009 (EST) OK guys, this is still just a page of text......

--[[User:Z3126328|Jin Lee]] 14:50, 3 September 2009 (EST) I want to make a timeline?

--[[User:S8600021|Mark Hill]] 08:42, 21 August 2009 (EST) z3187802 has contacted me and has been away sick. He should still complete his components of the group project.

Our group is Sum, Vishnnu, Juliana and Jenny. Today in the lab we have decided to research the RABBIT! [http://embryology.med.unsw.edu.au/OtherEmb/Rabbit.htm/ Rabbit embryology from Mark Hill]

(Juliana's email belebele85@msn.com)

----
This is apparently what we need to include in our case study:
#Timeline of Embryo Development - how long (SUM)
#Staging - are there species specific staging, what occurs when (SUM)
#History of Model Use - when was it first used, (JULIANNA)
#Genetics - chromosome number, sequencing (JENNY)
#Abnormal Development (VISHNNU)
#Current Embryology Research - research papers and findings (VISHNNU)

Hey guys, maybe we should add a section comparing rabbit to human development
--[[User:Z3185685|Sumaiya Rahman]] 16:45, 6 August 2009 (EST)

That sounds like a good idea Sum....seeing that human development is the primary theme of the course, not including it would be criminal!. -vishnnu

Report:
* Links to resources and discussions are to be posted on the group talk page, the project page is for the actual assignment
* Final assignment will be marked by another group and everyone will be given a marking criteria
* No information should be obtained from Wikipedia and all information (tables & graphs included) must be referenced
* Please feel free to suggest any further topics which can be included

== Research: ==
So i think the main rabbit used in research is the oryctolagus cuniculus. Lets focus mostly on that (or at least i, Jenny, will since im going genetics). This link is great for the specific genetics: [http://www.ncbi.nlm.nih.gov/nuccore/AJ001588/ Oryctolagus cuniculus complete mitochondrial genome]

Here's some stuff about benefits of modeling from a textbook. I haven't yet written as my own so its still the authors material. Just thought it might benefit us all (and raise our morale as we thought the rabbit might suck..but it doesn't!) We're not "submitting" this as our own work so technically we're not yet copyrighting their material.
Ive cited the book here and the website i got it from:
[http://books.google.com.au/books?id=RY0rXE2HgqsC&pg=PA344&lpg=PA344&dq=rabbit+embryology+genetics&source=bl&ots=rbr3CuBRxY&sig=p8055w9oYQmsQeuN78mgXBGmRK4&hl=en&ei=NI2KStaQJIvSsQOEpMjEDQ&sa=X&oi=book_result&ct=result&resnum=3#v=onepage&q=&f=false/ Cibelli, J., Lanza, R., Campbell, K. and West, M. 2002. Principles of Cloning. Academic Press]

“Rabbits were one of the first species in which blastomere nuclear transfer succeeded; as a model species, rabbits placed a central role in developing the micromanipulation technologies in embryos.” Other advantages for using rabbits are:

# “The costs to animal procurement, animal care, and oocyte production in rabbits are relatively low compared to large animals.” e.g. a cow embryo is 30x more expensive that a rabbit embryo
# “The developmental biology of rabbit embryos and fetuses resembles more closely that of large farm animals than that of rodent model species, including the transition from maternal to embryonic control of embryo development.”
# “The pregnancy of rabbits is relatively short (1 month), allowing rapid evaluation of fetal and postnatal development. In comparison, the gestation length for cattle is 9x longer.”
# “The sizeable milk production of rabbits allows their use as test animals for therapeutic protein expression in milk, or as a living bioreactor.”
# “Rabbits are induced ovulators. Domesticated rabbits are nonseasonal breeders and produce multiple offspring in one litter. These reproductive patterns make the use of rabbits for reproductive research highly efficient.”

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Here are some links i (sum) found which may help. Need to go through all the info and sort it out, But there are a couple of good diagrams.

'''Links for group assignment'''

http://www.reproduction-online.org/cgi/reprint/48/1/43

http://books.google.com/books?id=RY0rXE2HgqsC&pg=PA344&dq=rabbit+embryo+stages&as_brr=3#v=onepage&q=rabbit%20embryo%20stages&f=false - good for what studies in rabbit embryo have been used for. And has a good table for embryological stages!!

http://books.google.com/books?id=ljAKtC-iIrIC&pg=PA264&dq=rabbit+embryo+stages&as_brr=3#v=onepage&q=rabbit%20embryo%20stages&f=false

http://books.google.com/books?id=73bbKzqRvLsC&pg=PA156&dq=rabbit+embryo+stages&lr=&as_brr=3#v=onepage&q=rabbit%20embryo%20stages&f=false - picture of implantation

http://books.google.com/books?id=aZ7DQYFyxswC&pg=PA122&dq=%22rabbit+development+stages%22&lr=&as_brr=3#v=onepage&q=&f=false
-------
Hi I(Juliana) uploaded file, you guys can have a look.
Go to 'Upload File' tab and click ' early growth of rabbit trophoblast' file.

-------------
also I found an interesting article!
'''An Electron Microscope Study of the Embryology of the Intercalated Disc in the Heart of the Rabbit'''
Alan R. Muir
The Journal of Biophysical and Biochemical Cytology, Vol. 3, No. 2 (Mar. 25, 1957), pp. 193-202
Published by: The Rockefeller University Press

http://info.library.unsw.edu.au/cgi-bin/local/access/ej-access.cgi?url=http://links.jstor.org/sici?origin=sfx%3Asfx&sici=0095-9901(1957)3%3A2%3C193%3AAEMSOT%3E2.0.CO%3B2-S
--

[[User:Z3126328|Jin Lee]] 10:48, 25 August 2009 (EST)

----------------
I found helpful book in the library
'''Bensley's Practical Anatomy of the Rabbit 8thE by E.Horne Craigie, Toronto, University of Toronto Press 1948'''
--[[User:Z3126328|Jin Lee]] 13:27, 27 August 2009 (EST)

==Vishnnu's Research==

'''Background reading (Vishnnu)'''

Hey everyone. I'm starting my background reading section where I shall describe my research resources. They contain a summary and a link to the resource itself. I shall keep this "notes" section updated with each new entry I add.

'''Notes:'''

*Articles 1 & 2 - Juliana this could be useful to you.

*Article 2 - Sum this could be useful to you.

*Articles 3 & 4 - Abnormal development articles (added: 02/09/2009)

*Articles 5 & 6 - Abnormal development articles (added: 13/09/2009)

'''Article 1'''

'''The rabbit as a model for reproductive and developmental toxicity studies''' --[[User:Z3187802|Vishnnu Shanmugam]] 21:05, 30 August 2009 (EST)

''Robert H. Foote and Edward W. Carney'' ''Reproductive Toxicology 14 (2000) 477–493'' ''Department of Animal Science, Cornell University, 204 Morrison Hall, Ithaca, New York 14853-4801, USA Developmental and Reproductive Toxicology, ''The Dow Chemical Company Midland, Michigan 48674, USA''

'''Summary'''

This is a review article of a study looking at the use of rabbits in toxicological studies. The article describes the advantages in using the rabbit experimental model as opposed to the rodent model (mice & rats) and outlines the differences that make toxicological studies on rabbit embryos more accurate than rodents to resemble similar toxicological effects in human embryos. The article describes various techniques that can be used (eg. blood collection from marginal ear vein, artificial insemination, embryo collection) and solutions to some common problems that researchers face when using animal models. Very interesting article with a great quote from Robert Koch to open the eyes of researchers to other animal models:

“Gentlemen, never forget that mice are not human beings”

Want to find out more? Follow the link!

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6TC0-41SBGDH-1&_user=37161&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_acct=C000004218&_version=1&_urlVersion=0&_userid=37161&md5=4db60dc9352996fc4865b9d781b0128d

'''Article 2'''

'''Developmental stages in the rabbit embryo: guidelines to choose an appropriate experimental model''' --[[User:Z3187802|Vishnnu Shanmugam]] 21:05, 30 August 2009 (EST)

''S. Beaudoin; P. Barbet; F. Bargy''
''Fetal Diagnosis and Therapy; Nov/Dec 2003; 18, 6; Academic Research Library''
''pg. 422''

'''Summary'''

The article describes the various stages in the developing rabbit embryo and the rationale for using rabbits to study normal and abnormal embryology. The article details normal developments in the rabbit embryo and compares it to the developing human embryo. By making this comparison the article argues for the validity of rabbit embryology to better understand human embryology and also suggests that due to the similarities in the developing rabbit and human embryos, experiments on rabbit embryo’s yield more reliable results for human embryology. The article has some rare images on normally developing rabbits and breaks the developmental stages down (in days) describing the observable characteristics that form (eg. Limb development & body formation).
I have decided to use the image provided in the journal.

Definitely worth reading people, follow the link!

http://content.karger.com/produktedb/produkte.asp?typ=fulltext&file=FDT2003018006422

'''Article 3'''

'''Acheiropodia is caused by a genomic deletion in C7orf2, the human orthologue of the Lmbr1 gene''' --[[User:Z3187802|Vishnnu Shanmugam]] 04:32, 2 September 2009 (EST)

''P. Ianakiev, M. J. van Baren, M. J. Daly, S. P. A. Toledo, M. G. Cavalcanti, J. Correa Neto, E. Lemos Silveira, A. Freire-Maia, P. Heutink, M. W. Kilpatrick, P. Tsipouras''
''Am. J. Hum. Genet. 68:38–45, 2001''
''Department of Pediatrics, University of Connecticut Health Center, Farmington, CT;''
''Department of Clinical Genetics, Erasmus University, Rotterdam;''
''Whitehead Institute for Biomedical Research, Cambridge, MA;''
''LIM/25-D, University of Sao Paulo School of Medicine,''
''And Private Practice, Sao Paulo;''
''Private Practice, Porto Alegre, Brazil;''
''Department of Genetics, UNESP-Universidade Estadual Paulista, Botucatu SP, Brazil''

'''Summary'''

The article describes the developmental abnormality Acheiropodia can be passed down genetically from parent to offspring. Acheiropodia (also known as Horn Kolb Syndrome) is a condition where the distal extremities of the embryo fail to form. Although it is not fatal, the individual endures a very difficult life without hands and feet. The article notes that the disorder only affects the development of the limbs and has no other reported manifestations. The article defines this to be an autosomal recessive disorder which means that two copies of an abnormal gene must be present in the affected individual in order for the disease to develop. Thus, each parent passes an abnormal gene to the offspring. It is interesting to note the process of the malformation from genotype to phenotype: small deletions on the chromosomes produce abnormal genes, the abnormal genes are then passed down to the offspring, the offspring that inherits two of the abnormal genes is unable to code for the correct proteins and as a result, there is failure in normal development of limb extremities in the embryo phenotype. The article also has a shocking image of an individual with Acheiropodia which highlights the extent to which it can impact a person’s life and the urgent need to find a cure.

Read more about the exact nature of the abnormal gene using the link.

http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=1109034

'''Article 4'''

'''Epidemiology of congenital clefts of the lip and palate''' --[[User:Z3187802|Vishnnu Shanmugam]] 04:32, 2 September 2009 (EST)

''JOHN C. GREENE'' ''D.M.D. ,M.P.H.'' ''Public Health Rep. 1963 July; 78(7): 589–602''

'''Summary'''

This review article combines research to study the factors causing the developmental abnormalities cleft palate and cleft lip in populations. “Cleft palate (palatoschisis)” and “cleft lip (cheiloschisis)” are the terms used to describe the non- fusion of the upper lip, hard or soft palate and typically occur during the gestation phase of embryonic development. The article tables the occurrence of cleft palate and cleft lip in populations of people in various cities across the world. It also compares the occurrence of cleft palate and cleft lip in males and females. The article finds that the incidence of cleft palate and cleft lip is:

*Is random in males and females (ie. Occurs approximately evenly in both sexes)

*Is random in people living in different cities

*Is higher in children of mothers over the age of 35

*Is higher in white populations and lower in the negro populations which suggests possible role of environmental factors

*No concrete proof that cleft palate and cleft lip is hereditary

*Is higher in rats exposed to radiation and those fed riboflavin

*Is higher in rabbits and other lab animals exposed to higher stress through cortisone injections

Although the article is now quite ancient, it is interesting to note the incidence of cleft palate and cleft lip among people. It also shows the historical foundation of research into the causes of cleft palate and cleft lip through animal experimentation.

Read more about cleft palate epidemiology using the link.

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1915191

'''Article 5'''

'''Chromosome abnormalities in human embryos''' --[[User:Z3187802|Vishnnu Shanmugam]] 00:10, 13 September 2009 (EST)

''Santiago Munne & Jaques Cohen The Center for Reproductive Medicine and science of Saint Barnabas Medical Center, New Jersey, USA Human Reproductive Update 1998, Vol. 4, No. 6 pp. 842-855 European Society of Human Reproduction and Embryology''

'''Summary'''

As the title suggests, this article focuses on chromosomal abnormalities in the developing human embryo. To understand this article, it is necessary to first establish some basic definitions that are used throughout the article. Aneuploidy can be defined as the occurrence of one or more extra or missing chromosomes leading to an unbalanced chromosome number. Although most babies with an unbalanced amount of chromosomal material miscarry during the first trimester of pregnancy, those that are born have crippling conditions such as:

* Birth defects

* Turner's syndrome (disorder where a female child is born with only 1 X chromosome)

* Down's syndrome (disorder where child is born with 3 copies of chromosome 21)

* Edward's syndrome (disorder where child is born with 3 copies of chromosome 18)

* Patau's syndrome (disorder where child is born with 3 copies of chromosome 13)

* Klinefelter's syndrome (disorder where male child is born with 2 copies of the X chromosome and 1 Y chromosome)

Polyploidy is a type of aneuploidy where the baby has three, four, or more sets of chromosomes instead of the two present in diploids. Chromosomal mosaicism is when different cells within an individual, who has developed from a single fertilized egg, have a different chromosomal makeup. Most commonly there will be some cells with a typical number of chromosomes (46 chromosomes) and other cells with an altered number or structure of chromosomes.

The article explores the possible causes of chromosomal abnormalities resulting from pregnancy though techniques such as IVF (In-Vitro Fertilization) and ICSI (Intracytoplasmic Sperm Injection). It also analyses the role of FSH (follicle stimulation hormone), temperature, water and light in chromosomal abnormalities.

The article finds:

* High FSH concentration increases likelihood of chromosomal abnormalities

* ICSI & IVF techniques have increased likelihood of chromosomal abnormalities

* Chromosomes exhibit temperature sensitivity and changes in temperature can cause chromosomal abnormalities

Although the article makes a number of findings, it is yet to be backed up with convincing evidence; the article has some really cool images of the developing embryo soon after fertilization. Overall, an interesting read.

Interested? Follow the link!

http://humupd.oxfordjournals.org/cgi/reprint/4/6/842.pdf

'''Article 6'''

'''Evaluation of the Safety and Pharmacokinetics of the Multi-Targeted Receptor Tyrosine Kinase Inhibitor Sunitinib During Embryo–Fetal Development in Rats and Rabbits''' --[[User:Z3187802|Vishnnu Shanmugam]] 00:10, 13 September 2009 (EST)

''S. Patyna, J. Haznedar, D. Morris, K. Freshwater, G. Peng, J. Sukbuntherng, G. Chmielewski, and D. Matsumoto''
''Pfizer Global Research and Development, San Diego, California''
''Roche LLC, Palo Alto, California''
''Pfizer Global Research and Development, Kalamazoo, Michigan''
''Xenoport Inc., Santa Clara, California''
''Pfizer Global Research and Development,'' ''Groton, Connecticut '' ''Birth Defects Research (Part B) 86:204–213 (2009)''

'''Summary'''

The article looks at how toxicity affects embryo-fetal development. The article describes the abnormal changes that occur when Sunitinib (an oral inhibitor of multiple receptor tyrosine kinases) is administered to pregnant rabbits and rats. This experiment was performed in an attempt to mirror the effects of antiangiogenic agents used in cancer treatment. Sunitinib is an antiangiogenic agent and the use of antiangiogenic agents is not recommended for treating cancer in pregnant patients because of the potential harm to embryo-fetal development. Angiogenesis (the formation of blood vessels) plays a critical role in embryo–fetal development and antiangiogenic agents slow down and/or stop the formation of blood vessels in order to control cancer and stop its spread. In pregnant patients however, this has the potential to adversely affect the developing embryo and these adverse effects is what is investigated in this article.

The article finds the antiangiogenic agent Sunitinib at toxic levels can result in:

* Embryo death

* Fetal skeletal malformations including vertebrae malformation and cleft lip/palate

* Teratogenic effects in rabbits

* Decreased maternal and fetal body weight

This article is a recent study and provides important findings regarding the use of antiangiogenic agents, especially during pregnancy. Although the maternal effects are minimal, the adverse effects to the embryo are significant and permanent. The article makes good use of tables and graphs to juxtapose pieces of information and to show trends. It is very interesting to note the extent to which chemicals can impact the vulnerable developing embryo.

Read more at link. (Use institutional login from UNSW computers)

http://www3.interscience.wiley.com/journal/122262246/abstract?CRETRY=1&SRETRY=0

------
thank you so much Vishnuu~~^^ from Juliana
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I also changed the format if you guys dont mind--[[User:Z3126328|Jin Lee]] 18:33, 31 August 2009 (EST)
----

Hey '''Vishnuu''', that link you found with the stages is awesome! thanks so much. Do you know if i am allowed to use the embryo pics in that article on our wiki page?? i'm not sure about the copyright rules. It says at the bottom of the article "Reproduced with permission of the copyright owner. Further reproduction prohibited without permission."
Does this mean we can only provide a link to it on our page? if so that's a shame, because those pics were fantastic!! '''SUM'''

Oh i also added an introduction - sum

Hey Sum,
Unfortunately, since its copyright protected we can't use the image directly......but there is a way of getting around it....You can modify the image using picture editing tools, then simply reference where the original picture came from and state that it has been modified by you. Alternatively, you can trace around the picture and provide only an outline (this will be very difficult to do with detailed pictures, a good picture editing software is recommended). Either way according to whats written under '''editing basics''' we need to include a picture that has been drawn up ourselves in the project. Also, not sure if you are aware, but the project is NOT due on Thursday (3rd September), Dr. Hill has very generously given everyone an extension till after mid-session break. --[[User:Z3187802|Vishnnu Shanmugam]] 02:35, 2 September 2009 (EST)

==Julianna's Research==
[http://netvet.wustl.edu/species/rabbits/rabtmodl.txt]
HISTORY OF THE RABBIT (IN RESEARCH)

A. Discovered in Spain about 100 B.C.
B. Domesticated in the 1500's
C. Standardization of breeds in 1800's
1. Research Uses
a. 1852: Rabbits have DL-hyoscyamine
(a) Can survive belladonna
(b) Endogenous atropine esterase
b. 1884: Pasteur develops rabies vaccine
c. 1891: Heape performs embryo transfer
(a) Influence on phenotype of the
uterine environment
d. 1908: Ignatowsky produces atherosclerosis
(a) Fed diets of milk, meat, and
eggs
(b) Produced intimal lesions
(c) Believed lesions due to protein
e. 1928: Demonstrated intranuclear development
of herpes virus
f. Graafian follicle was first observed
g. Coat colors and Mendelian inheritance
h. Immunology studies
i. Testing of human use products
j. Basic science studies
k. Diagnostic requirements
l. Eye Research
m. Pyrogen testing
n. Fetal drug induced teratology
o. Parasite research

LITERATURE REVIEW OF RABBIT USE

A. 1956 to 1800 ... Over 8000 citations
B. 1966 to 1987 ... 130,000 citations linking the rabbit to
all areas of research
C. 1988 to present ... 821 citations under the search
criteria: Rabbit: Model: Human Disease
D. Numbers of Rabbits Used (APHIS; ILAR records 1989)

1967 504,500
1978 439,986
1982 547,312
1983 466,810
1984 529,101
1985 544,621
1986 521,773
1987 534,385

ADVANTAGES OF USING RABBITS
A. Provides repeatability of animal model studies
B. Large enough for single samples
C. Many stocks/strains as animal models
D. Easily managed
E. Quality of immunologic products
F. Ease of reproductive control

DISADVANTAGES OF USING RABBITS
A. Most colonies are a storehouse of diseases
B. Extremely variable to responses to general anesthetics

[http://www.ncbi.nlm.nih.gov/pubmed/18430597]
The rabbit as a model to study asthma and other lung diseases.Keir S, Page C.
Sackler Institute of Pulmonary Pharmacology, Division of Pharmaceutical Sciences, 5th Floor Hodgkin Building, King's College London, Guy's Campus, London SE1 9RT, UK.

No single animal model is able to reproduce all the features of human asthma. However, the similarities between neonatally immunised rabbits and human asthma highlight the value of this model in the investigation of asthma pathophysiology and in the development of therapeutic agents. Airway inflammation and airway responses to various stimuli including histamine, adenosine 5'monophosphte and antigen in allergic rabbits have shown similarities with the responses observed in asthmatics. Furthermore, functional studies in rabbit airways show they are poorly responsive to capsaicin as are human airways. Chronic pre-treatment with capsaicin desensitises the TRPV(1) receptor enabling studies into the effect of this drug in both rabbits and man. The allergic rabbit model has been used extensively in assessing the various classes of anti-asthma drugs and is sensitive to similar drugs as patients with asthma, including beta-adrenoceptor agonists, corticosteroids, phosphodiesterase inhibitors and theophylline. This article highlights the usefulness of the rabbit as a species to study lung biology.

[http://www.ncbi.nlm.nih.gov/pubmed/8447943]
Effects of strain and embryo transfer model (embryos from one versus two donor does/recipient) on results of cryopreservation in rabbit.Vicente JS, García-Ximénez F.
Departamento de Ciencia Animal, Universidad Politécnica de Valencia, Spain.

Differential effects of 2 transfer models for normal thawed embryos of 1 donor doe were studied on the offspring rate and their embryo survival at birth from 3 selected rabbit strains (SY and SB: synthetic strains, NZ: New Zealand White). Morulae were obtained 64-66 h post-coitum from 93 adult does treated with 25 IU of hCG (SY:36, NZ:27, SB:30). Morphologically normal morulae were frozen in the presence of 1.5M DMSO and stored in liquid nitrogen. Normal thawed embryos were transferred into the oviducts of synchronized recipient does of the same strain 48 h after being injected with 25 IU of hCG (SY:28, NZ:21, SB:24). Each recipient received embryos from 1 (single transfer) or 2 different donor does (double transfer). Significant differences were observed in the post-thawing percentage of normal embryos between strains (SY:95 +/- 1% and SB:85 +/- 3%, P < 0.05; NZ: ,91 +/- 2%). After transfer, no significant differences were observed in pregnancy rate and offspring rate between the transfer models, whereas significant differences were only found in survival rate when all transfers were analyzed (double: 24 +/- 4% vs single: 14 +/- 3%, P < 0.05). An effect of strain was detected in the pregnancy rate (NZ: 33% vs SB: 71%, P < 0.05; SY: 61%) and in the survival rate per donor doe on pregnant recipient doe (SY: 42 +/- 5 vs SB: 19 +/- 5, P < 0.05; NZ: 34 +/- 7%). These results suggest a differential embryo sensitivity with respect to their genetic origin in both the freezing-thawing and transfer procedures.

--[[User:Z3126328|Jin Lee]] 13:06, 3 September 2009 (EST)

[http://www.ncbi.nlm.nih.gov/pubmed/14064965?log$=activity]GROSS EFFECTS ON RABBIT EMBRYOS AND MEMBRANES OF X-IRRADIATION IN THE BLASTOCYST STAGE.

[http://www.ncbi.nlm.nih.gov/pubmed/11139224?ordinalpos=408&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum]Onset of zygotic transcription and maternal transcript legacy in the rabbit embryo.Brunet-Simon A, Henrion G, Renard JP, Duranthon V.
Laboratoire de Biologie du Développement, INRA, Jouy en Josas Cedex, France.

Onset of zygotic transcription is progressive from the one-cell stage onward in the rabbit embryo. Maternal transcripts remain fairly stable until the 8-16 cell stage when major transcriptional activation of the zygotic genome takes place. To understand the mechanisms of the maternal-to-zygotic transition in the genetic information governing development, we asked whether a progressive synthesis of zygotic transcripts takes over the maternal molecules, or whether the synthesis of zygotic transcripts is very abrupt and independent of the persistence of the maternal counterparts. To answer this question, we set up mRNA differential display experiments comparing the mRNA content of rabbit embryos at different stages during the preimplantation period. We isolated eight zygotic transcripts whose synthesis is abruptly turned on at the 8-16 cell stage. These transcripts are involved in general cellular metabolism and their maternal counterparts are still present up to the four-cell and even the 8-16 cell stage. This identification of early zygotic transcripts suggests that global long range modifications of chromatin structure result in a rapid increase in transcription rates during the major transcriptional activation of the zygotic genome.

[http://www.ncbi.nlm.nih.gov/pubmed/11245264?ordinalpos=409&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum]
Reconstruction of the heteroparental diploid condition in rabbit zygotes by nuclear transfer.Escribá MJ, García-Ximénez F.
Departamento de Ciencia Animal Universidad Politécnica de Valencia, Spain. mescriba@dca.upv.es

Studies on genomic imprinting showed that parental genomes have complementary roles during embryogenesis, are both essential and need to be synchronized in their embryonic stage for successful development to term. To our knowledge, these studies have not been performed in species other than mice. We studied the in vitro and in vivo development of reconstructed zygotes by combining female haploid nuclear donors and androgenetic hemizygous recipients. Haploid donor embryos at the 8- or 32-cell stage were obtained from electroactivated young rabbit ova (eight pulses maximum, consisting of 0 6 kVcm(-1) for 60 microsec each, 38 min apart) which were further cultured for 24 h or 32 h. Couplets formed by both the haploid male hemizygous recipients and haploid female donor cells were electrofused (2.2 kVcm(-1) for 60 microsec duration each, 30 min apart) and their nuclear configuration determined 122 of those fused (43%: 122/286) were diploid. Reconstructed diploid zygotes developed in vitro up to the compacted morula, blastocyst and hatched stages (1/8-nuclei x 50%, 18% and 9% vs. 1/32-nuclei: 47%, 25% and 19%; P > 0.05), respectively. In embryo transfer assays, both 1/32-reconstructed zygotes and control, non-manipulated zygotes were transferred to synchronized does Four live reconstructed fetuses (4/49: 8 1% survival rate) and five in regression stage (9/49: 18% implantation rate) were observed on Day 21 post-ovulation, whereas from control zygotes, 11 fetuses were alive (11/53 21% fetal survival rate) and 2 degenerated (13/53 x 24 5% implantation rate). Similar results were obtained from a final experiment, in which development was allowed to progress to term. Six live rabbit pups derived front experimentally reconstructed zygotes (11%; 6/54) and three fetuses in regression stage were obtained; values slightly lower than those derived from non-manipulated and transferred control zygotes (18% 9/50, live born rate).

[http://www.ncbi.nlm.nih.gov/pubmed/11589623?ordinalpos=412&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum]
Effects of leukaemia inhibitory factor on endometrial receptivity and its hormonal regulation in rabbits.Liu CQ, Yuan Y, Wang ZX.
Shanghai Institute of Planned Parenthood Research, Shanghai, P. R. China.

The effects of hormones on production of leukaemia inhibitory factor (LIF) and the uterine receptivity in rabbits were studied. In ovariectomised rabbits, LIF protein was not detected in control but upregulated by progesterone alone. Oestrogen had a slightly negative effect when the rabbits were treated with both oestrogen and progesterone. Mifepristone (Mi) inhibited the progesterone-stimulated production of LIF in rabbit uterus. The transfer of embryos to LIF-treated recipients significantly increased pregnancy rate (70%) and implantation rate (27%) as compared with control (pregnancy rate=40% and implantation rate=17%). The transfer of embryos to LIF and mifepristone-treated recipients significantly decreased pregnancy rate (30%) and implantation rate (9%). The results indicated that LIF protein had a beneficial effect on uterine receptivity and mifepristone prevented this effect. Copyright 2001 Academic Press.

[http://www.ncbi.nlm.nih.gov/pubmed/8447943]
Effects of strain and embryo transfer model (embryos from one versus two donor does/recipient) on results of cryopreservation in rabbit.Vicente JS, García-Ximénez F.
Departamento de Ciencia Animal, Universidad Politécnica de Valencia, Spain.

Differential effects of 2 transfer models for normal thawed embryos of 1 donor doe were studied on the offspring rate and their embryo survival at birth from 3 selected rabbit strains (SY and SB: synthetic strains, NZ: New Zealand White). Morulae were obtained 64-66 h post-coitum from 93 adult does treated with 25 IU of hCG (SY:36, NZ:27, SB:30). Morphologically normal morulae were frozen in the presence of 1.5M DMSO and stored in liquid nitrogen. Normal thawed embryos were transferred into the oviducts of synchronized recipient does of the same strain 48 h after being injected with 25 IU of hCG (SY:28, NZ:21, SB:24). Each recipient received embryos from 1 (single transfer) or 2 different donor does (double transfer). Significant differences were observed in the post-thawing percentage of normal embryos between strains (SY:95 +/- 1% and SB:85 +/- 3%, P < 0.05; NZ: ,91 +/- 2%). After transfer, no significant differences were observed in pregnancy rate and offspring rate between the transfer models, whereas significant differences were only found in survival rate when all transfers were analyzed (double: 24 +/- 4% vs single: 14 +/- 3%, P < 0.05). An effect of strain was detected in the pregnancy rate (NZ: 33% vs SB: 71%, P < 0.05; SY: 61%) and in the survival rate per donor doe on pregnant recipient doe (SY: 42 +/- 5 vs SB: 19 +/- 5, P < 0.05; NZ: 34 +/- 7%). These results suggest a differential embryo sensitivity with respect to their genetic origin in both the freezing-thawing and transfer procedures.

[http://www.ncbi.nlm.nih.gov/pubmed/14564113]
'''Developmental stages in the rabbit embryo: guidelines to choose an appropriate experimental model.'''Beaudoin S, Barbet P, Bargy F.
Department of Pediatric Surgery, Groupe Hospitalier Cochin-Saint-Vincent de Paul, Paris, France. sylvie.beaudoine@svp.ap-hop-paris.fr

Researchers involved in the field of congenital malformations are often forced to work on an animal model. Both accurate description of its normal development and comparative staging with human development will be mandatory. To complete the lacking medical literature, we herein provide such data for the rabbit model. Sampled rabbit embryos were staged using the Carnegie criteria, in order first to determine if they were consistent with the rabbit developmental pattern, and second to compare this pattern with the human one. Our results show a suitable comparison of rabbits and humans in early developmental stages, except for the neural growth. Copyright 2003 S. Karger AG, Basel

2009 Group Project 1

2009-10-14T11:48:18Z

Z3185685: /* Staging */

[[File:Rabbits.png|right|400 px]]

== '''THE RABBIT (ORYCTOLAGUS CUNICULUS)''' ==

==Introduction==

[[File:Isidro_Martinez.jpg‎|left|175 px]]

Several characteristics of the rabbit make it an excellent model for study. Many studies have resulted in the development and improvement of various micro-manipulation techniques such as the production of transgenic rabbits. The rabbit is an appropriate animal model as the results from many experiments are significant to that of other mammals, including humans. (55)

A rabbits potential for reproduction is high, breeding from the early stages of 3 to 4 months of age. A mature female rabbit can be pregnant from 6 to 8 months in a year, producing up to 30 to 40 young in this time. (56)

==History of Model Use==

'''WHY are we using rabbits?'''

ADVANTAGES
*Provides repeatability of animal model studies
*Large enough for single samples
*Many stocks/strains as animal models
*Easily managed
*Quality of immunologic products
*Ease of reproductive control

DISADVANTAGES
*Most colonies are a storehouse of diseases
*Extremely variable to responses to general anesthetics

'''Brief timeline of rabbit embryo model use'''

*1672- de Graaf found the Graffian follicle.
*1890- Walter Heape succeeded first mammalian embryo transfer
*1906- FT Lewis discovered the development of the lymphatic system in rabbit embryos.
*1941- Dr. Pincus succeeded in keeping rabbit embryos developing in the test
*1968- Edwards and Gardner successfully performed the first known embryo biopsy on rabbit embryos

=== Regnier de Graaf (1641–1673) ===
[[image:Ovary_Graaf.jpg|thumb|250px|left|drawing of ovary]]
[[File:Regnier de Graaf.jpg|right]]

'''Discovery of the Graafian Follicles'''

In 1672 de Graaf published ''The Generative Organs of Women'', which was primarily a study of development in the rabbit. When de Graaf discovered large, round welling on the ovaries of rabbits, he assumed they were mammalian eggs. De Graaf also described the corpus luteum.

He summarised the previous works from anatomists, but unable to experience the amazing benefits made by microscopy.
But Antonie van Leeuwenhoek (A microbiologist, 1632 - 1723) argued that the structures now known as Graafian follicles could not be eggs. Haller suggested that the egg might be formed by the coagulation of the fluid within the Graafian follicle. De Graaf noted that the “egg” did not contain a tiny embryo, but he thought it did contain the “germ” of the future organism. (3)

=== Walter Heape (1855-1928) ===
'''First case of embryo transfer experiments'''

On 27 April 1890, Walter Heape (a professor and physician at the University of Cambridge, England) transferred rabbit embryos from one mother to another. (7) One rabbit mother became pregnant and delivered young from the transferred embryos. This was the first mammalian embryo transfer experiment to be successfully completed. His embryo transfer work in perspective as it relates to other contributions of this pioneer in reproductive biology.(7)

In 1891, Walter Heape had been conducting research on reproduction in numerous animal species. Working with two species of rabbits, he flushed embryos from the rabbit fallopian tubes of one breed (Angora) and placed them into the uterus of a recently mated Belgian hare. In the resulting litter, there were 4 Belgians and 2 Angoras. Heape proved that it was possible to take preimplantation embryos and transfer them to a gestational carrier without affecting their development.(7)

===Dr. Gregory Goodwin Pincus (1903-1967) ===

'''Contraceptive pill'''

Dr. Pincus began studying hormonal biology and steroidal hormones early in his career. His first breakthrough came when he was able to produce in vitro fertilization in rabbits (by using chemicals) in 1934. Throughout their hormonal contraceptive research Pincus, along with reproductive physiologist Min Chueh Chang, found out progesterone would act as an inhibitor to ovulation. They co-invented the combined oral contraceptive pill.[2][6]

===Genetic Diagnosis===
In 1968, Robert Edwards and David Gardner reported the successful sexing of rabbit blastocysts, setting the first steps towards PGD (Preimplantation Genetic Diagnosis). It was not until the 1980s that human IVF was fully developed, which coincided with the breakthrough of the highly sensitive polymerase chain reaction (PCR) technology. Handyside and collaborators' first successful attempts at testing were in October 1989 with the first births in 1990 though the preliminary experiments had been published some years earlier. In these first cases, PCR was used for sex determination for patients carrying X-linked diseases.(12)

==Timeline of Embryo Development==

The following is a timeline, adapted from Cibelli (2002), of the main events of preimplantation development in rabbits. The time is measured in hours post-mating and shows the embryo stage (cell number) in each time scale.

[[File:Morula1.JPG|right|200 px|thumb|A day 2 early morula]]

'''12-14:''' Oocyte; Fertilization

'''18-20:''' Zygote; Pronuclear formation

'''24-26:''' Two cell

'''30-32:''' Four cell

'''38-40:''' Eight cell; Maternal-zygotic transition

'''46-48:''' Sixteen cell

'''54-56:''' Morula (32 cell); Compaction and transport to uterus

'''64-66:''' Compact morula (64 cell); Morula-blastocyst transition

'''76-78:''' Early blastocyst (128 cell)

'''84-86:''' Expanded blastocyst (256 cell); Blastocoels expansion

'''94-96:''' Hatched blastocyst (512 cell); Hatching

The following shows a diagrammatic representation of the relative sizes of rabbit embryos. The sizes do not include the embryonic coverings such as the zona pellucida and mucin coat. This diagram has been adapted from Warner (2003).

[[File:Sizes.JPG]]

The following timelines show a comparison of the developmental stages between human and rabbit embryos. They have been adapted from Derelanko (2008). "The similarities of this developmental pattern in humans and rabbits, suggests that the same growth increment is required to achieve the same stage. The main difference observed between human rabbit gestational duration is due to the fetal growth phase. The reason for this may be due to birth weight, lifetime and the neural complexity of the species." (59)

[[File:Timeline_rabbit.JPG]]

The following timelines have been adapted from a study carried out by Beaudoin et al. on the development of rabbit embryos.

==='''Body Form'''===

'''8.5 days''': Embryo thickens. First somites appear. Rostral neuropore closes. Caudal neuropore remains open

'''9.5 days''': Dorsal curvature begins. Cardiac mass bulges under cephalic pole.

'''10.5 - 13.5 days''': Dorsal curvature increases. Body thickens. Softening of the cephalic domination straightens the embryo.

'''17.5 days''': Neck becomes visible.

==='''Limb Development'''===

''' 9.5 days''': Rostral limb bud appears

'''10.5 days''': Caudal limb bud appears

'''12.5 days''': Hand plate becomes present. Limbs become disposed.

'''13.5 days''': Foot plate and finger rays become visible.

'''14.5 days''': Rostral and caudal limbs become parallel.

'''15.5 days''': Elbow appears.

'''16.5 days''': Fingers start to elongate.

'''17.5 days''': Knee becomes visible

'''19.5 days''': Hands and feet merge on the midline. Three segments of limbs become distinguished.

==='''Abdominal Wall Development'''===

'''9.5 days''': Abdominal wall is limited to the embryonic pedicle under the cardiac mass.

'''13.5 days''': First intestinal loops appear in the umbilical cord.

'''14.5 days – 17.5''': Rapid intestinal development in the cord.

'''15.5 days''': Abdominal vesicles can be observed.

'''16.5 days''': Cecal bud becomes present outside the abdomen

'''18.5 days''': Bowel returns to the abdominal cavity and umbilical ring closes.

==='''Cephalic Development'''===

'''9.5 days''': One cerebral vesicle can be seen. Pharyngeal arches as optic vesicle are present.

'''10.5 days''': Three arches are distinguished in the cephalic pole.

'''11.5 days''': Three cerebral vesicles present. Optic plate is distinguished.

'''12.5 days''': Face develops nasal, maxillar and mandibular buds. Lens vesicle is closed. Five cerebral vesicles exist.

'''14.5 days''': The ear becomes refined. Face can be distinguished from the brow.

'''18.5 days''': Eyelid appears, covering the eyes.

==Staging==

The following stages have been adapted from Beaudoin et al. (2003). Table 1 represents at each age its corresponding stage defined by the Carnegie classification

{| class="wikitable" style="text-align:center; width: 800px; height:1000px" border="1"
|+'''Table 1. Rabbit developmental stages using Carnegie classification'''

|- style="height:50px"
! '''Stage''' !! '''Days''' !! '''Event''' !! '''Image'''
|- style="width:200px"
! width="50" | 10
| width="50" | 8.5 || First somites appear, rostral neuropore closes
|- style="height:75px"
! 12
| 9.5 || Rostral limb bud, embryonic pedicle, caudal neuropore closes, one cerebral vesicle, pharyngeal arches, completion of optic vesicle
| [[file: 9.5new.JPG|100px]]
|- style="height:75px"
! 13
| 10.5 || Dosral C-shaped curvature, caudal limb bud, prominent cardiac swelling, four pharyngeal arches
| [[file: 10.5new.JPG|100px]]
|- style="height:75px"
! 14
| 11.5 || Three cerebral vesicles, optic plate, mesonephric ridge
|- style="height:75px"
! 15
| 12.5 || Hand plate, wheel ray limbs, lens vesicle closes, five cerebral vesicles, facial buds, vertebrae
| [[file: 12.5new.JPG|100px]]
|- style="height:75px"
! 16
| 13.5 || Foot plate, finger rays, prominent liver, intestinal loops, auricular hillocks
| [[file: 13.5new.JPG|100px]]
|- style="height:100px"
! 19
| 14.5 || Cuboidal body, trunk straightens, parallel limbs, toe rays, modeled face, visible auricle
| [[file: 14.5new.JPG|100px]]
|- style="height:75px"
! 20
| 15.5 || Elbow, fingers elongate, notches between toe rays
| [[file: 15.5new.JPG|100px]]
|- style="height:75px"
! 21-22
| 16.5 || Toes free, cecal bud in intestinal hernia
| [[file: 16.5new.JPG|100px]]
|- style="height:75px"
! 22-23
| 17.5 || Knee, neck, eyelids
| [[file: 17.5new.JPG|100px]]
|- style="height:75px"
! 23
| 18.5 || Hands and feet join at the midline, closure of abdominal wall, eyelids cover eyes
| [[file: 18.5new.JPG|100px]]
|-
| colspan="4" align="center"| Following this stage fetal appearance is completed, organogenesis is achieved
|}

==Genetics==

===Sequencing===
The National Human Genome Research Institute selected the European rabbit (Oryctolagus cuniculus) for whole genome sequencing to enhance their understanding of the human genome and use it experimentally for an animal model for human disease. (8)

The rabbit has been sequenced twice by The Broad Institute as part of the mammalian genome project. It is now currently undergoing 7 more sequencing projects. Its sequencing is made by the Whole Genome Shotgun (WGS) and assembly method. (9) This is when genomic DNA is sheared into small pieces of approximately 2000 base pairs which are then cloned into plasmids and sequenced on both strands. Once the contig fragments are read, realigned and reassembled by computer algorithms, it will give the overall sequence. (10) (11) The image below shows diagramatically how the two types of sequencing are different. The same techniques are used for sequencing the human genome (in 2003). [A contig is a set of overlapping DNA segments, derived from a single source of genetic material, from which the complete sequence may be deduced.

The whole genome shotgun (WGS) has serious gaps, yet the information has already proven useful for immunological as well as in silico studies. Deeper 7x coverage started in September 2007. The NCBI Rabbit Genome Resources site has links to searches for genes in the assemblies of the 2x WGS sequence at Ensembl and UCSC.(12) [http://www.broadinstitute.org/models/europeanrabbit/ Rabbit Genome Project]

[[File:WGS_sequencing.gif‎|center|800 px]]

===Genome===
The Rabbit genome was published by two groups (9)
# Lindblad-Toh,K., Chang,J.L., Gnerre,S., Clamp,M. and Lander,E.S. published their admission of 84024 bases on May 5th 2005 to The Broad Institute (USA) by shotgun sequencing
# Di Palma,F., Heiman,D., Young,S., Gnerre,S., Johnson,J., Lander,E.S. and Lindblad-Toh,K. published their admission of 84024 bases on August 3rd 2009 to The Broad Institute (USA) by shotgun sequencing.
The rabbit's genome is sequenced and on display in the Nucleotide Data Bank. It is too long to produce here. A link to the data bank is provided: [http://www.ncbi.nlm.nih.gov/nuccore/256946799/ Rabbit Genome from the Nucleotide Data Bank]

[[File:8cellembryo.jpg|thumb|Individual mitochondria (arrowheads) of an 8cell Rabbit embryo]]

The rabbit genome was sequenced in 2005 by Ensembl and managed to produce: (13)
* 2,076,044,328 supercontigs (ordered Contigs with gaps)
* 495 Known protein-coding genes
* 11,357 Projected protein-coding genes
* 2,343 RNA genes
* 212,581 Gene exons
* 20,311 Gene transcripts

For further research the taxonomy ID number for the Rabbit is: 9986 [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=9986&lvl=3&lin=f&keep=1&srchmode=1&unlock/ Taxonomy Data]

===Mitochondrial Genome===
The mitochondiral genome (mtDNA) of the rabbit was sequenced on November 14th 2006 with 17245 base pairs/nucleotides in circular form. Apparently the "length is not absolute due to the presence of different numbers of repeated motifs in the control region".
PMID 9653643

The image to the right shows the mitochondria during cell division and multiplication in embryo development.

=== Chromosomes ===
Over the years there have been various data suggesting the diploid chromosomal number for the rabbit may range from 22-42. However through recent research and an abundance of trials suggest that the rabbit does indeed have 22 different chromosome pairs existing in each cell of the rabbit. (16)(17) The sex chromosomes of the rabbit are of X-Y type convincingly (17). In a study in Bombay it confirmed that a rabbit has 2n = 44 chromosomes. There were 21 pairs of autosomes, out of which 1 to 6 were metacentric, 7 to 11 submetacentric, 12 to 17 subtelocentric and 18 to 21 acrocentric, plus the sex chromosomes. The image to the left shows a female rabbit with no chromosomal abnormalities. (19)

'''Comparison to human chromosome:'''

Rabbit chromosomes 12, 19 and X were found to be completely homologous to human chromosomes 6, 17 and X, respectively. All other human chromosomes were homologous to two or sometimes three rabbit chromosomes. (14) Chromosome 12 was shorter than chromosomes 13 and 14. (15) The image below illustrates the human chromosome (2n = 46).

[[File:Drawn chromosome.jpg|left|400 px]]

[[File:Karyotypehuman.gif|right|500 px]]

'''Abnormalities'''

These are generally more apparent during early embryo development in blastocysts from delayed fertilization. Some examples of abnormal development include cases of: (18)
* hypoploidy; 1 chromosome missing from a pair (2n = 43),
* double hypoploidy; 2 chromosomes missing from 2 different pairs (2n = 42),
* mosaicism (different chromosomal makeup in some cells).

Another study also found these abnormalities as well as: (19)
* autosomal trisomy (3 autosomes per pair),
* triploidy (extra set of chromsomes),
* mixoploidy (unequal number of chromosome sets in adjacent cells), and
* short arm deletion (deletion of parts of chromosomes).

A specific abnormality occurring in rabbits is the x-linked tremor. There is a mutation in exon 2 of the prteolipid-protein (PLP 1) gene, corresponding to the end of the first potential transmembrane domain of the protein. This disorder affects myelination of the central nervous system. OMIA ID:12 [http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=full_report&list_uids=100009169&log$=omiamaingene| Gene:100009169]

==Abnormal Development==

Abnormal embryological development is a vast field of study that has been the subject of recent research papers. Our investigation of abnormal development in rabbit embryology will focus on abnormalities commonly found in both rabbit and human embryos. We will explore the nature of these abnormalities in both humans and rabbits.

[[File:Normal v Abnormal.jpg|right|300 px|thumb|Brain MRI of patient with Hydrocephalus (left) compared to a normal brain (right). An obvious increase in ventricular size and a significant decrease in brain size is present.]]
[[File:Ventricle_Expansion.jpg|right|300 px|thumb|CSF accumulation in ventricles of brain increasing intracranial pressure.The pressure from the expanding ventricles force the brain and skull to grow outwards abnormally.]]

'''Hydrocephalus'''

Annually, one in every 1000 children born in Australia have hydrocephalus. Hydrocephalus occurs when excessive cerebrospinal fluid (CSF) accumulates in the brain and can result in severe disability and even death because the disorder can result in complete or near complete destruction of the cerebral cortex (22).

Children born with hydrocephalus typically exhibit abnormally large head circumference and bulging cranial fontanels as a result of increased intracranial pressure on the brain from the accumulating CSF (22,23). As CSF accumulates in the ventricles and CSF compartments of the brain, it expands forcing the brain to grow outward. The outward growing brain places pressure on the skull which in turn also grows outwards giving rise to an abnormally large head circumference and bulging cranial fontanels (22,24). It is generally acknowledged that children with hydrocephalus have mental retardation, often to the degree of being “vegetative” (24).

The serious consequences of this disease mean that much research is necessary to unearth methods of prevention and effective treatment. One of the modes of studying hydrocephalus is to use the rabbit experimental model where hydrocephalus can be induced in rabbit embryo’s. The injection of silicone oil into the cisterna magna of the brain is one way of inducing hydrocephalus in the rabbit embryo. The silicone oil obstructs the normal flow of CSF resulting in CSF accumulation in the brain leading to hydrocephalus (25). Another method of inducing hydrocephalus in rabbit embryo’s is by intentional vitamin A deprivation of pregnant dams. The vitamin A deficiency results in raised intracranial CSF pressure and aqueduct stenosis causing poor circulation of CSF leading to hydrocephalus (26,27). Although the exact function of vitamin A on brain development and CSF regulation is not fully understood, it is clear that Vitamin A has an important role in brain development and its normal functioning (27).
[[File:Rabbithhdrocephalus.jpg|center|300 px|thumb|Young rabbit with hydrocephalus caused by Vitamin A deficiency. Note the abnormally shaped cranium inflamed in appearance.]]

[[File:SpinabifidaMeningocele1.jpg|right|300 px|thumb|Spina Bifida Meningocele has characteristic damage to the meninges of the spinal cord which are pushed out through an opening in the vertebrae as a cyst filled with CSF.]]
[[File:SpinaBifidaMyelomeningocele.jpg|right|300 px|thumb|Spina Bifida Myelomeningocele is the most severe form of spinabifida where the damaged spinal cord protrudes out with damaged meninges as a cyst filled with CSF.]]
[[File:SpinaBifidaOcculta1.jpg|right|300 px|thumb|Spina Bifida Occulta is the least severe as the spinal cord and meninges are undamaged.]]

'''Spina Bifida'''

In Australia, the risk of spina bifida is 1 in every 500 pregnancies. Spina bifida is a type of neural tube defect where vertebrae (which normally cover and protect the spinal cord) are not completely formed but are divided resulting in the defective spinal cord and its coverings to protrude through the opening (28,29).

There are three main types of Spina Bifida differentiated by their characteristic features:

1)Spina Bifida Meningocele characterized by normal spinal cord, divided outer vertebrae and meninges surrounding the spinal cord protruding from the divided vertebrae as a cyst (1,28).

2)Spina Bifida Myelomeningocele characterized by split outer vertebrae with spinal cord and its meninges protruding from the divided vertebrae as a cyst. Commonly found at lumbar vertebral level (1,28,29).

3)Spina Bifida Occulta characterized unfused vertebral arches and exposed vertebral canal. Spinal cord and its meninges still located in vertebral canal (1,28).

All forms of spina bifida are potentially fatal and in those where the spinal cord is damaged severe consequence arise including and paralysis and loss of sensation at and below the level of damage spinal cord damage (29,33). There is a lot of Spina bifida research using rabbit models to test the effective methods of correcting spina bifida. The occurrence of natural spina bifida in rabbits is rare and for experimental purposes it can be surgically created in rabbit fetuses during gestation (31,32). The process involves aesthetical sedation of the maternal rabbit at day 22 of gestation; a midline laparotomy performed and the desired type of spina bifida lesion created on the exposed fetus using forceps. Different methods for correcting spina bifida can then be tested and its effectiveness analysed (30,33,34).
[[File:Rabbitspinabifida1.jpg|center|350 px|thumb|Rabbit newborn with Spina Bifida. Note the unfused, divided vertebrae and exposed spinal cord.]]

'''Brachydactylia & Acheiropodia'''

[[File:Malformation1.jpg|right|150 px|thumb|Acheiropodia in rabbit characterized by amputations of the limbs and extremities.]]

[[File:Rabbitmalformation3.jpg|left|150 px|thumb|X-Ray study of rabbit limbs with malformed phalanges due to Brachydactylia.]]

Brachydactylia and Acheiropodia are genetic disorders characterized by skeletal malformation of the hands and feet (36,36). In Brachydactylia, the malformations commonly involve abnormal shortening of fingers and toes due to poorly formed or absent bones (35). Acheiropodia is characterized by more severe skeletal malformations including bilateral amputations of the distal upper and lower extremities as well as aplasia of the hands and feet. Although it is not fatal, the individual endures a very difficult life without hands and feet (37).

The inheritance mechanism of this diseases can has been studied through experiment using rabbits. Rabbits with abnormal genes coding for Brachydactylia and Acheiropodia are selected and bred to produce offspring with the disease (36). Brachydactylia and Acheiropodia are autosomal recessive disorders which means that two copies of an abnormal gene must be present in the affected individual in order for the disease to develop. Thus, each parent passes an abnormal gene to the offspring (35,36). The process of the malformation progresses from genotype to phenotype; small deletions on the chromosomes produce abnormal genes, the abnormal genes are then passed down to the offspring, the offspring that inherits two of the abnormal genes is unable to code for the correct proteins and as a result, there is failure in normal development of limb extremities in the embryo phenotype (37,38).

==Current Embryology Research==

There is currently great excitement in research involving rabbits in the fields of transgenesis, cloning and stem cells. We shall explore research in these areas by discovering some of the techniques used and how they have been applied to the rabbit model.

[[File:Trans1.jpg|right|170 px]]
[[File:Trans2.jpg|right|170 px]]
[[File:Trans3.jpg|right|170 px]]
[[File:Trans4.jpg|right|170 px]]
[[File:Trans5.jpg|right|170 px]]

'''Transgenic rabbit'''

A transgenic organism is one whose genome also contains genes from another species (39). The aim of creating a transgenic organism is to obtain a favorable characteristic in the organism’s phenotype (41). This desired characteristic of phenotype is obtained by altering the organism’s normal genotype to include the gene from another species with the desired characteristic (39,40).

The production of a transgenic organism involves several steps summarized below:

1) The chromosome and the desired gene on it are identified in an organism (39).

2) The gene is isolated from its DNA strand. This involves “cutting” it out of its DNA strand using enzymes called restriction endonucleases. The restriction endonucleases cut DNA at specific site so the desired gene can be removed from the DNA strand. The cut ends are known as “sticky ends” (39,40).

3) Separate DNA sequences for regulation sometimes have to be added to ensure the gene will work (40).

4) The gene is then inserted with a promoter sequence into the fertilized egg cell of a new organism producing recombinant DNA (39,44). To do this, firstly the new organism’s cell DNA must first be cut and the desired gene incorporated into it. The same enzymes are used to cut the new organism’s cell DNA because the DNA stands from the two different organisms will form matching sticky ends that will be attracted to and connect with each other in a process is called “annealing” (39,40,44).

5) DNA ligases are sealing enzymes found in all living organisms that help make and repair DNA (39,40). The DNA ligases are added to the annealed DNA fragments to help strengthen the bonds of the new recombinant DNA. The recombinant DNA is now transferred into the new organism’s fertilized egg by microinjection (44).

6) As the embryo develops and the recombinant genetic code read, new proteins are synthesized which code for the new desired phenotype characteristic in the transgenic organism (39,40).

Transgenic rabbits can be created in the laboratory by gene microinjection into the fertilized rabbit oocyte (44). In April 2000, a transgenic rabbit named Alba was born containing a gene from a Pacific Northwest jellyfish. The gene which was injected into a fertilized albino rabbit oocyte allows the rabbit to synthesize the green fluorescent protein (GFP) that is characteristic of the Pacific Northwest jellyfish. When illuminated correctly, Alba glows a bright green (43,46).

Transgenic rabbits have important research purposes. Transgenic rabbits can be created to model retinal degeneration (44). Retinal degeneration is a common problem with aging and diseases such as diabetes, and frequently leads to complete blindness (42). A genetic retinal degeneration disease called retinitis pigmentosa (RP) is created in these rabbits by introducing the “Pro347Leu” mutation of the rhodopsin gene into fertilized rabbit eggs (43,44). As the rabbit grows, it develops the disease which becomes progressively worse (45).
The use of these transgenic rabbits ultimately leads to better understanding of the disease and more effective treatments (42). [[File:Transgenic rabbit.jpg|center|250 px|thumb|"Alba" A trangenic rabbit with a gene from a Pacific Northwest jellyfish that allows it to synthesize the green fluorescent protein (GFP) of the jellyfish.]]

[[File:Crabbit 1.jpg|right|170 px]]
[[File:Rabbit2.jpg|right|170 px]]
[[File:Rabbit3.jpg|right|170 px]]
[[File:Crabbit 4.jpg|right|170 px]]

'''Cloning'''

Cloning is a method of producing genetically identical organisms. The principle of cloning relies on “tricking” an egg cell to begin rapidly dividing into an embryo (39). In the normal fertilization process, two haploid sex cells unite to form a diploid zygote which begins rapidly dividing into an embryo (40). By replacing the haploid egg cell nucleus with a diploid somatic cell nucleus, the egg cell is tricked into thinking it is fertilized and hence begins rapidly dividing to form an embryo (39,40,41).

The process of cloning involves several steps summarized as the following using a rabbit example:

1) A somatic cell is obtained from a rabbit and the nucleus removed (39).

2) An egg cell is obtained from a donor rabbit and the nucleus of the egg cell removed using an enucleation needle. The cell is now called an enucleated egg cell (egg cell without a nucleus) (39,41).

3) The nucleus of the somatic cell is inserted into the enucleated egg cell (41).

4) The cell is now stimulated to divide by applying pulses of electric current (39).

5) The rapidly dividing cell develops in culture for a few days forming the early embryo (40,41).

6) The embryo is then implanted into the uterus of another rabbit similar to the egg cell donor. This rabbit is called the surrogate mother (40,41).

7) The embryo develops and the surrogate mother gives birth to a rabbit fetus with near identical genotype of the somatic cell donor (the small genomic difference is caused by the fetus obtaining mitochondrial DNA from the egg cell donor) (39,41).

The cloning of rabbits has been achieved by inserting the diploid nucleus of a rabbit fibroblast (the principal cells in connective tissue) into an enucleated oocyte (49). There is currently much focus on the creation of controversial but revolutionary interspecies hybrid embryos where the nucleus from a human somatic cells are implanted into an enucleated egg cell of another animal (50). The resulting embryo (known as a chimera) will be almost completely human genotype but will have genome from the other animal (48). In 2003, scientists at the Shanghai Second Medical University fused human cell with rabbit eggs creating the first human-rabbit hybrid using the nucleus transfer technique. The hybrid embryo developed in culture for a few days before it was destroyed and the stem cells harvested (47,48). The purpose of the research into creating hybrid embryos is to provide researchers with human stem cells for experimentation into cures for diseases such as cystic fibrosis, Alzheimer’s and Motor Neuron disease as human stem cell are difficult to obtain (50).

[[File:Rabbit clone.jpg|center|450 px|thumb|(A) Cloned rabbits (5 month old) from nuclear transfer technique. (B) The male rabbit whose fibroblasts were used as the nuclear donors. The cloned rabbits have almost identical genome to the male donor.]]

'''Stem Cells'''
[[File:HES.jpg|right|200 px|thumb|Human Embryonic Stem cell (hES).]]
[[File:Rabbit knee.jpg|right|200 px|thumb|Stem cell induced cartilage repair of knee in rabbit.]]

Stem cells are unspecialized cells which are able to continuously reproduce themselves and under appropriate conditions, differentiate into all the various specialized cells of the organism such as cardiac cells, neurons and blood cells (39,40). Adults have a small number of stem cells when compared to a developing embryo and the stem cell of an embryo more easily obtained (41). Human embryonic stem cells (hES) derived from the inner mass of the preimplantation blastocyst have the potential to differentiate into all cell types in the human body and thus are valued by researchers (50). However, due to ethical and political issues, the obtaining and experimentation on human embryonic stem cells is difficult and alternate means are needed as stem cell provides potentially new treatments for a range of diseases (54).

Rabbits can be used both in the obtaining of stem cell for experimentation and also as recipients of stem cells to cure diseases. The human-rabbit hybrid embryo provides a method of obtaining stem cells for experimentation and these stem cells possess many similar properties to human stem cells, including expression of surface markers, special growth requirements, capabilities of self renewal, formation of embryonic body and differentiation into cells of all three germ layers (53).

Stem cell experimentation on rabbits also focuses on transplanting stem cell into rabbits to treat specific diseases. A study at Zhejiang University where a research team transplanted human mesenchymal stem cell into New Zealand white rabbits with myocardial infarction recoded regeneration of vascular structure and improvement in cardiac function. The research team noted the potential of stem cells in differentiating into specialized cardiac cells when subjected to the specific conditions of the rabbit heart (52).

Another study at Hallym University tested the effectiveness of transplanting mesenchymal stem cells from New Zealand white rabbits into damaged cartilage in the knees of other New Zealand white rabbits. In the experiment, mesenchymal stem cells were obtained from the rabbit bone marrow and injected into the knees of other rabbits that had cartilage in their knees surgically damaged. The research team were able to conclude notable cartilage recovery in the rabbits with the mesenchymal stem cell injection and the potential of mesenchymal stem cells to differentiate into fibroblasts, adipoblasts, osteoblasts and chondroblasts (51,53).

The findings in stem cell experimentation with in rabbits yielded positive results and potentially opens a new field of research in the use of stem cell to treat a range of diseases in humans.

==References==

# Dr Mark Hill 2009, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G [6]
# E.Horne Craigie, University of Toronto Press 1948, Bensley's Practical Anatomy of the Rabbit 8th Edition
# Ankum WM, Houtzager HL, Bleker OP (1996). "Reinier De Graaf (1641-1673) and the fallopian tube". Human Reproduction Update 2 (4): 365–9. doi:10.1093/humupd/2.4.365. PMID 9080233.
# Jocelyn HD, Setchell BP (December 1972). "Regnier de Graaf on the human reproductive organs. An annotated translation of Tractatus de Virorum Organis Generationi Inservientibus (1668) and De Mulierub Organis Generationi Inservientibus Tractatus Novus (1962)". Journal of Reproduction and Fertility. Supplement 17: 1–222.
# Jay, V. (2000). "A portrait in history. The legacy of Reinier de Graaf". Archives of Pathology & Laboratory Medicine 124(8): 1115–6.
# Lois N Magner. "A history of the Life Sciences" 3rd edition
# J. D. Biggers. (1991). Walter Heape, FRS: a pioneer in reproductive biology.Centenary of his embryo transfer experiments Laboratory of Human Reproduction and Reproductive Biology, and Department of Cellular and Molecular Physiology, Harvard Medical School, Boston, MA 02115, USA
# National Center for Biotechnology Information. (June 16, 2009). ''Rabbit Genome Resources'', Retrieved August 20, 2009, from [http://www.ncbi.nlm.nih.gov/projects/genome/guide/rabbit/ NCBI Rabbit Genome Site]
# The Broad Institute. (2008). ''Rabbit Genome Sequencing Project''. Retrieved only August 29, 2009, from [http://www.broadinstitute.org/models/europeanrabbit/ Rabbit Genome Sequencing Project]
# Campbell, M. A. (2002). ''Sequencing Whole Genomes: Hierarchical Shotgun Sequencing v. Shotgun Sequencing'' Retrieved August 31, 2009, from [http://www.bio.davidson.edu/courses/GENOMICS/method/shotgun.html/ Shotgun Sequencing - 1]
# Trivedi, B. (2000). ''Sequencing the Genome''. Retrieved September 4, 2009, from [http://www.genomenewsnetwork.org/articles/06_00/sequence_primer.shtml Shotgun Sequencing - 2]
# Mage, R. (2008). Rabbit genome sequencing update: genes of immunological interest found in the 2x genome assemblies, ENCODE, and the 7x trace archive. ''Journal of FASEB'' 22(Retrieved September 5, 2009, from [http://www.fasebj.org/cgi/content/meeting_abstract/22/2_MeetingAbstracts/559/ Rabbit Genome & its Immunological Interest]
# Ensembl (2009). ''Rabbit (Oryctolagus cuniculus)''. Retrieved September 5, 2009, from [http://www.ensembl.org/Oryctolagus_cuniculus/Info/Index/ Ensembl Genome Project]
# Korstanje, R. et al. (1999) Complete homology maps of the rabbit (Oryctolagus cuniculus) and human by reciprocal chromosome painting. ''Cytogenetics and cell genetics'' ''86''(3-4), 317-322. Retrieved September 6, 2009, from [http://cat.inist.fr/?aModele=afficheN&cpsidt=1189693/ Complete homology maps of the rabbit Article] "PMID 10575232"
# Brunner, R., Knopp, A., Rudolph, W. (n.d). Rabbit chromosome analysis by image processing. ''Journal of Applied Rabbit Research''.
# DebMark Rabbit Education Resource (2006). ''Rabbit Genetics''. Retrieved September 6, 2009, from [http://www.debmark.com/rabbits/genetics.htm/ Rabbit Genetics]
# Painter, T. (2009) Studies in mammalian spermatogenesis VI. The chromosomes of the rabbit. ''Journal of Morphology''. ''43''(1): 1-43.
# Hofsaess, F., and Meacham, T. ( 1995) Chromosome abnormalities of early rabbit embryos. ''Journal of Experimental Zoology''. ''177'' (1): 9-11 [http://www3.interscience.wiley.com/journal/110490865/abstract/ Chromosome abnormalities]
# Martin-Deleon, P., Shaver, E., and Gammal, E. (1973) Chromosome abnormalities in rabbit blastocysts resulting from spermatozoa aged in the male tract. ''Fertility and Sterility''. ''24''(3):212-219.
# Patil, M. et al (2004) Chromosome analysis of domestic rabbit. ''The Journal of Bombay Veterinary College''. ''12'' (1 and 2)
#Biggers J.D (1991) Walter Heape FRS: a pioneer in reproductive biology. centenary of his embryo transfer experments.''Journals of reproduction and fertility''. ''93''(1)
# Stoodley, M (2006). Hydrocephalus. Prince of Wales Clinical School. Retrieved from [http://www.brainaustralia.org.au/AZ_of_Brain_Disorders/hydrocephalus]
# National Institute of Neurological Disorders and Stroke (2008, February). Hydrocephalus Fact Sheet. Retrieved from [http://www.ninds.nih.gov/disorders/hydrocephalus/detail_hydrocephalus.htm]
# Lewin, R (1999). Is Your Brain Really Necessary?. 24) Developmental Medicine & Child Neurology, 41. Retrieved from [http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=176431]
# Bigio, M.R, & Bruni J.E (1991). Silicone oil-induced hydrocephalus in the rabbit . Child's Nervous System, 7(2), Retrieved from [http://www.springerlink.com/content/b011477724837152/]
# Geelen, J.A (1974). A case of hydrocephalus and meningoencephalocele in a rabbit, caused by aqueductal malformation. Laboratory Animals, 8(2), Retrieved from [http://la.rsmjournals.com/cgi/content/abstract/8/2/167]
# LAMMINGX, G.E (1954). 27) Hydrocephalus in Young Rabbits Associated with Maternal Vitamin A Deficiency. British Journal of Nutrition, 8(2), Retrieved from [http://journals.cambridge.org/download.php?file=%2FBJN%2FBJN8_04%2FS0007114554000554a.pdf&code=10bb1dbc4a9e57a091f4e05f6aebbcf2]
# Carney, A (2008, February ). Spina bifida. Retrieved from [http://www.spinabifida.asn.au/]
# Better Health Channel (2008, October ). Spina bifida explained . Retrieved from [http://www.betterhealth.vic.gov.au/bhcv2/bhcarticles.nsf/pages/Spina_bifida_explained]
# Peeters, M.C, Viebahn, C, & Hekking, J.W (1998). Neurulation in the rabbit embryo . Anatomy and Embryology, 197(3), Retrieved from [http://www.springerlink.com/content/1efyteewgetjlwyg/]
# George, T.M, & Fuh E (2003). Review of Animal Models of Surgically Induced Spinal Neural Tube Defects: Implications for fetal surgery. Pediatric Neurosurgery , 39(2), Retrieved from [http://content.karger.com/produktedb/produkte.asp?typ=fulltext&file=PNE2003039002081]
# Pedreira, D.A, & Valente P.R (2002). A Different Technique to Create a 'Myelomeningocele-Like' Defect in the Fetal Rabbit. Fetal diagnosis and therapy, 17(6), Retrieved from [http://content.karger.com/ProdukteDB/produkte.asp?Doi=65388]
# Patten, B.M (1953). Embryological stages in the establishing of myeloschisis with spina bifida. The American journal of anatomy, 93(3), Retrieved from [http://deepblue.lib.umich.edu/handle/2027.42/49611]
# Pedreira, D.A, & Valente P.R (2003). Successful Fetal Surgery for the Repair of a 'Myelomeningocele-Like' Defect Created in the Fetal Rabbit. Fetal Diagnosis and Therapy, 18. Retrieved from [http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowPDF&ProduktNr=224239&Ausgabe=229041&ArtikelNr=69378]
# Lecklitner, M.L, & Douglas K.P (1986). Osteoscintigraphy and brachydactylia of the hand . European Journal of Nuclear Medicine and Molecular Imaging, 12(9), Retrieved from [http://www.springerlink.com/content/t82l77282x579102/]
# Greene, H.S, & Saxton J.A (1938). HEREDITARY BRACHYDACTYLIA AND ALLIED. ABNORMALITIES IN THE RABBIT. THE JOURNAL OF EXPERIMENTAL MEDICINE , 69. Retrieved from [http://jem.rupress.org/cgi/reprint/69/2/301.pdf]
# P. Ianakiev, M. van Baren, M. Daly, S. Toledo, M. Cavalcanti, J. Neto, E. Silveira, A. Freire-Maia, P. Heutink, M. Kilpatrick. Acheiropodia Is Caused by a Genomic Deletion in C7orf2, the Human Orthologue of the Lmbr1 Gene. The American Journal of Human Genetics, 68. Retrieved from [http://linkinghub.elsevier.com/retrieve/pii/S0002929707624707]
# Walbaum, R, Hazard, C, & Cordier, R (1976). Brachydactylia with symphalangism, probably autosomal recessive . Human Genetics, 33(2), Retrieved from [http://www.springerlink.com/content/m630p6880661486n]
# Campbell, N.A, & Reece, J.B (2002). Biology 6th Edition. USA: Benjamin Cummings.
# Solomon, E.P, Berg, L.R, & Martin, D.W (2002). Biology 6th Edition. USA: Thompson Learning.
# Glanville, A.R (2008). Scientifica. NSW, Australia: Millennium House.
# Lund, R.D (2008). Saving Vision with Skin Cells. Retrieved from [http://www.blindness.org]
# Jones, B.W, & Marc R.E (2008). Computational Molecular Phenotyping and Excitation Mapping in the P347L. Retinal Degeneration , (2986), Retrieved from [http://prometheus.med.utah.edu/]
# Kondo, M, Sakai, T, & Ueno, S (2009). Generation of a Transgenic Rabbit Model of Retinal Degeneration. Investigative Ophthalmology and Visual Science, 50. Retrieved from [http://www.iovs.org/cgi]
# Punzo, C, Chen, B, & Roesch, K (2009). PHOTORECEPTOR DEATH IN MOUSE MODELS OF RETINITIS PIGMENTOSA. Retrieved from [http://genepath.med.harvard.edu]
# Zimmer, M (2008). Alba. Retrieved from [http://www.conncoll.edu/ccacad/zimmer/GFP-ww/cooluses8.html]
# Scott, C (2006, May 1). Chimeras in the crosshairs. Nature Biotechnology , 24, Retrieved from [http://www.nature.com/nbt/journal/v24/n5/abs/nbt0506-487.html]
# Mott, M (2005, January 25). Animal-Human Hybrids Spark Controversy. National Geographic News, Retrieved from [http://theyfly.com/PDF/Nat.%20Geo.%20Animal-Human%20Hybrids.pdf]
# Li, S, & Chen X (2006). Rabbits generated from fibroblasts through nuclear transfer . Society for Reproduction and Fertility, 131. Retrieved from [http://www.reproduction-online.org/cgi/reprint/131/6/1085]
# Minger, S (2007). Interspecies SCNT derived human embryos. Regenerative Medicine, 2(2), Retrieved from [http://www.futuremedicine.com]
# Koga, H, Shimaya, M, & Muneta, T (2008). Local adherent technique for transplanting mesenchymal stem cells as a potential treatment of cartilage defect. Arthritis Research & Therapy, 10(4), Retrieved from [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2575632]
# Wang, J, Li, C, & Sun, Y (2005). Human bone marrow-derived mesenchymal stem cells transplanted into damaged rabbit heart to improve heart function. Journal of Zhejiang University Science, 6(4), Retrieved from [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1389731]
# Chen, Y, Liu, A, & Mao, W (2003). Embryonic stem cells generated by nuclear transfer of human somatic nuclei into rabbit oocytes. Cell Research , 13(4), Retrieved from [http://www.nature.com]
# Bethesda (2009, September 23). Stem Cell Information. Retrieved from [http://stemcells.nih.gov]
# Cibelli, J. B. (2002). Principles of cloning Amsterdam. Academic Press
# European rabbit (oryctolagus cuniculus) Retrieved 9/21/2009, 2009, from http://www.feral.org.au/content/species/rabbit.cfm
# Warner, S. (2003). Inositol transport in preimplantation rabbit embryos: Effects of embryo stage, sodium, osmolality and metabolic inhibitors Reproduction, 125(4), 479-493.
# Derelanko, M. J. (2008). The toxicologist's pocket handbook, second edition Informa HealthCare
# Beaudoin, S., Barbet, P., & Bargy, F. (2003). Developmental stages in the rabbit embryo: Guidelines to choose an appropriate experimental model Fetal Diagnosis and Therapy, 18(6), 422-427.

==Glossary==

Anesthetic - A drug that causes temporary loss of bodily sensations

Aplasia - The absence or defective development of a tissue or organ

Blastocyst - A stage of embryo development that occurs about five days after fertilisation when the embryo contains quite a few cells

Caudal - Situated towards the inferior or posterior end of the body

Cephalic - Relating to the head

Cerebral Aqueduct - A canal filled with cerebrospinal fluid within the midbrain

Cerebral Cortex - The layer of unmyelinated neurons (the grey matter) forming the cortex of the cerebrum of the brain

Cerebro Spinal Fluid (CSF) - A watery fluid which flows in the cavities within the brain and around the surface of the brain and spinal cord

Chromosome - Microscopic carriers of genetic material, composed of deoxyribonucleic acid (DNA) and proteins and appearing as rods under a microscope

Cisterna Magna - is one of three principal openings in the subarachnoid space between the arachnoid and pia mater layers of the meninges surrounding the brain

Diploid - A full set of genetic material, consisting of paired chromosomes one chromosome from each parental set

Dorsal - Position towards the back

Fontanel - Membranous gap between the bones of the cranium in an infant or fetus

Genome - All genetic information, the entire genetic complement and all of the hereditary material possessed by an organism. Made up of both chromosomal genome (inside the nucleus of the cell in the familiar form of chromosomes) and mitochondrial genome (outside the nucleus in the cytoplasm of the cell, usually in the form of one round chromosome (the mitochondrial chromosome))

Genotype - The genetic makeup of an organism

Glucocorticoids - A class of steroid hormones that bind to the glucocorticoid receptor (GR), which is present in almost every vertebrate

Haploid - A single set of chromosomes (half the full set of genetic material)

Laparotomy- Surgical incision into the abdominal wall; often done to examine abdominal organs

Ligases - Group of enzymes that catalyze the binding of two molecules

Oocyte - A female gametocyte that develops into an ovum after two meiotic divisions

Phenotype - The observable traits or characteristics of an organism, for example hair color, weight, or the presence or absence of a disease.

Pronuclear - Haploid nucleus before fusion of nuclei in fertilisation

Restriction Endonucleases - Enzymes that recognize and cleave specific DNA sequences, generating either blunt or single-stranded (sticky) ends

Retina - The thin layer of cells at the back of the eyeball where light is converted into neural signals sent to the brain

Rostral - Situated toward the oral and nasal region

Somite - Blocks of mesoderm on either side of the notochord and neural tube during development of the vertebrate embryo. Develop into muscles and vertebrae

Stenosis - Abnormal narrowing of a bodily canal or passageway

Weaning - Young become accustom to nourishment other than suckling

==Links to Research Laboratories and Researchers==

1) Transgenic lab: [http://www.dnavision.be/index.php]

Involved in development of transgenic organisms, DNA construction and phenotype analysis.

2) World Rabbit Science Association: (WRSA) [http://world-rabbit-science.com]

International Association where researchers exchange knowledge and encourage teaching, scientific research, practical experimentation, the collection and publication of statistics and documents relating to the rabbit. Even have their own journal called “World Rabbit Science”

Website provides contact with researchers, professors and veterinarians working with rabbits.

Example: Dr. Myriam Kaplan-Pasternak, Doctorate Veterinary Medicine, University of California, myriamsemail@gmail.com

3) American Veterinary Medical Association [http://www.avma.org]

The American Veterinary Medical Association (AVMA), established in 1863, is a not-for-profit association representing more than 78,000 veterinarians working in private and corporate practice, government, industry, academia, and uniformed services. Excellent website into animal research and has a range of veterinary journals.

{{Template:Projects09}}
[[Category:Rabbit]]
[[File:Example.jpg]]

File:18.5new.JPG

2009-10-14T11:35:45Z

Z3185685: This image shows an adapted representation of a rabbit embryo at 18.5 days. Image adapted from Beaudoin, S., Barbet, P., & Bargy, F. (2003). Developmental stages in the rabbit embryo: Guidelines to choose an appropriate experimental model Fetal Diagnosis

This image shows an adapted representation of a rabbit embryo at 18.5 days. Image adapted from Beaudoin, S., Barbet, P., & Bargy, F. (2003). Developmental stages in the rabbit embryo: Guidelines to choose an appropriate experimental model Fetal Diagnosis and Therapy, 18(6), 422-427

File:17.5new.JPG

2009-10-14T11:35:22Z

Z3185685: This image shows an adapted representation of a rabbit embryo at 17.5 days. Image adapted from Beaudoin, S., Barbet, P., & Bargy, F. (2003). Developmental stages in the rabbit embryo: Guidelines to choose an appropriate experimental model Fetal Diagnosis

This image shows an adapted representation of a rabbit embryo at 17.5 days. Image adapted from Beaudoin, S., Barbet, P., & Bargy, F. (2003). Developmental stages in the rabbit embryo: Guidelines to choose an appropriate experimental model Fetal Diagnosis and Therapy, 18(6), 422-427

File:16.5new.JPG

2009-10-14T11:35:02Z

Z3185685: This image shows an adapted representation of a rabbit embryo at 16.5 days. Image adapted from Beaudoin, S., Barbet, P., & Bargy, F. (2003). Developmental stages in the rabbit embryo: Guidelines to choose an appropriate experimental model Fetal Diagnosis

This image shows an adapted representation of a rabbit embryo at 16.5 days. Image adapted from Beaudoin, S., Barbet, P., & Bargy, F. (2003). Developmental stages in the rabbit embryo: Guidelines to choose an appropriate experimental model Fetal Diagnosis and Therapy, 18(6), 422-427

File:15.5new.JPG

2009-10-14T11:34:41Z

Z3185685: This image shows an adapted representation of a rabbit embryo at 15.5 days. Image adapted from Beaudoin, S., Barbet, P., & Bargy, F. (2003). Developmental stages in the rabbit embryo: Guidelines to choose an appropriate experimental model Fetal Diagnosis

This image shows an adapted representation of a rabbit embryo at 15.5 days. Image adapted from Beaudoin, S., Barbet, P., & Bargy, F. (2003). Developmental stages in the rabbit embryo: Guidelines to choose an appropriate experimental model Fetal Diagnosis and Therapy, 18(6), 422-427

File:14.5new.JPG

2009-10-14T11:34:18Z

Z3185685: This image shows an adapted representation of a rabbit embryo at 14.5 days. Image adapted from Beaudoin, S., Barbet, P., & Bargy, F. (2003). Developmental stages in the rabbit embryo: Guidelines to choose an appropriate experimental model Fetal Diagnosis

This image shows an adapted representation of a rabbit embryo at 14.5 days. Image adapted from Beaudoin, S., Barbet, P., & Bargy, F. (2003). Developmental stages in the rabbit embryo: Guidelines to choose an appropriate experimental model Fetal Diagnosis and Therapy, 18(6), 422-427

File:13.5new.JPG

2009-10-14T11:33:57Z

Z3185685: This image shows an adapted representation of a rabbit embryo at 13.5 days. Image adapted from Beaudoin, S., Barbet, P., & Bargy, F. (2003). Developmental stages in the rabbit embryo: Guidelines to choose an appropriate experimental model Fetal Diagnosis

This image shows an adapted representation of a rabbit embryo at 13.5 days. Image adapted from Beaudoin, S., Barbet, P., & Bargy, F. (2003). Developmental stages in the rabbit embryo: Guidelines to choose an appropriate experimental model Fetal Diagnosis and Therapy, 18(6), 422-427

File:12.5new.JPG

2009-10-14T11:33:08Z

Z3185685: This image shows an adapted representation of a rabbit embryo at 12.5 days. Image adapted from Beaudoin, S., Barbet, P., & Bargy, F. (2003). Developmental stages in the rabbit embryo: Guidelines to choose an appropriate experimental model Fetal Diagnosis

This image shows an adapted representation of a rabbit embryo at 12.5 days. Image adapted from Beaudoin, S., Barbet, P., & Bargy, F. (2003). Developmental stages in the rabbit embryo: Guidelines to choose an appropriate experimental model Fetal Diagnosis and Therapy, 18(6), 422-427

File:10.5new.JPG

2009-10-14T11:32:45Z

Z3185685: This image shows an adapted representation of a rabbit embryo at 10.5 days. Image adapted from Beaudoin, S., Barbet, P., & Bargy, F. (2003). Developmental stages in the rabbit embryo: Guidelines to choose an appropriate experimental model Fetal Diagnosis

This image shows an adapted representation of a rabbit embryo at 10.5 days. Image adapted from Beaudoin, S., Barbet, P., & Bargy, F. (2003). Developmental stages in the rabbit embryo: Guidelines to choose an appropriate experimental model Fetal Diagnosis and Therapy, 18(6), 422-427

File:9.5new.JPG

2009-10-14T11:31:49Z

Z3185685: This image shows an adapted representation of a rabbit embryo at 9.5days. Image adapted from Beaudoin, S., Barbet, P., & Bargy, F. (2003). Developmental stages in the rabbit embryo: Guidelines to choose an appropriate experimental model Fetal Diagnosis an

This image shows an adapted representation of a rabbit embryo at 9.5days. Image adapted from Beaudoin, S., Barbet, P., & Bargy, F. (2003). Developmental stages in the rabbit embryo: Guidelines to choose an appropriate experimental model Fetal Diagnosis and Therapy, 18(6), 422-427.

Talk:2009 Group Project 1

2009-10-14T09:08:15Z

Z3185685: /* Actual Changes Made */

== Lab 10 ==
--[[User:Z3283499|Antonio Lee]] 10:52, 2 October 2009 (EST) Hi everyone, I will be working with you during the Lab10 Tutorial and here is the news link and PDF of the manuscript for your group exercise. I encourage you to read the paper before the tutorial. Also, please indicate next to the questions below (using either your initials or student number) which one of the four questions you wish to address.
:'''Group 1 :''' [http://www.nature.com/nature/journal/v461/n7262/full/461354a.html '''Developmental biology: Asexual healing'''] in Nature News and Views - Nature 461, 354-355 (17 September 2009) [[Media:ANAT2341_Lab10_2009_Group 1 Reading.pdf|Manuscript (PDF): Mitochondrial gene replacement in primate offspring and embryonic stem cells]]

:Question 1. What is the background to the existing problem / disease condition? --[[User:Z3187802|Vishnnu Shanmugam]] 22:12, 2 October 2009 (EST)

Mitochondria are found in all eukaryotic cells and contain their own genome (mitochondrial DNA or mtDNA). Unlike the nuclear genome, which is derived from both the egg and sperm at fertilization, the mtDNA in the embryo is derived almost exclusively from the egg; it is of maternal origin.

Mutations in mitochondrial DNA (mtDNA) can lead to a range of chronic incurable diseases such as myopathies, neurodegenerative diseases, diabetes, cancer and infertility. Mutations in mitochondrial DNA could also contribute to other diseases such as Alzheimer’s,
Parkinson’s and Huntington’s diseases

A normal cell should be homoplasmic in its mitochondrial DNA, that is it should only contain one type of mitochondrial DNA. But if the cell has two or more types of mitochondrial DNA (a mixture of normal and mutated DNA) it is known as heteroplasmic and can lead to a range of diseases. These genetic mutations can also be passed to offspring causing disease.
1 in 3,500–6,000 are at risk or presently have a disorder from mutations in mitochondrial DNA. Disease progresses slowly and there are no cure. Limitations in assessing the extent heteroplasmy and accuracy in calculating the risks of developing mtDNA related disease means that a new approach is needed to tackle the problem.

:Question 2. What approach / method did the research team take to tackle / improve the problem?--[[User:Z3126328|Jin Lee]] 12:31, 7 October 2009 (EST)
:Working with rhesus macaque monkeys, the authors reconstructed mature oocytes containing the nuclear genome from one oocyte and the mitochondrial genome from another. To do this they removed the nuclear genetic material from one oocyte, leaving behind all of the mitochondrial DNA, then transferred it to another oocyte whose nucleus had been removed (a cytoplast), but which contained a full complement of mitochondrial DNA.

:Question 3. What was the breakthrough / major advancement OR failure / drawback? and why might this be of significance?
::Drawbacks - --[[User:Z3186093|Jenny Guy]] 22:43, 7 October 2009 (EST)
:::There were difficulties in visualising and isolating the intact chromosomes, as well as the mtDNA being susceptible to damage and translocation/movement. Visualization became easier after the development of techniques for DNA staining with fluorophores and looking under UV light during embryo cloning by the SCNT (somatic cell nuclear transfer). Successful implementation to avoid damage to the cytoplast during spindle removal involved using polarized microscopy. (p368) --[[User:Z3186093|Jenny Guy]] 14:12, 8 October 2009 (EST)
:Question 4. What are the next steps in moving forward? What are the next or new hurdles to overcome?

==Actual Changes Made==

'''Concise Version:''' (Everyone add their changes here)
# Removed cleft palate and cleft lip section (Abnormal development) --[[User:Z3187802|Vishnnu Shanmugam]]
# Altered references (current research and abnormal development) --[[User:Z3187802|Vishnnu Shanmugam]]
# Added picture guide for transgenic rabbit --[[User:Z3187802|Vishnnu Shanmugam]]
# Added picture guide for rabbit cloning --[[User:Z3187802|Vishnnu Shanmugam]]
# Removed newspaper image of rabbit (Current research) --[[User:Z3187802|Vishnnu Shanmugam]]
# Formatted pictures and text to reduce gaps in the assignment (current research and abnormal development) --[[User:Z3187802|Vishnnu Shanmugam]]
# Corrected spelling mistakes in images (current research and abnormal development) --[[User:Z3187802|Vishnnu Shanmugam]]
# Reviewed all images and have written a summary, original source, copyright information (current research and abnormal development) --[[User:Z3187802|Vishnnu Shanmugam]]
# Formatted the look of the genetics section, including 'abnormalities' --[[User:Z3186093|Jenny Guy]] 16:31, 14 October 2009 (EST)
# Fiddled with position of images in genetics section --[[User:Z3186093|Jenny Guy]] 16:31, 14 October 2009 (EST)
# Fixed spelling mistake in History - Jin Lee
# Sum have you changed anything? Haven't heard from you in a while! - Jenny
Yep jenny doing it now - had 4 major assessments due this week sorry! - Sum

'''Long Version:'''

--[[User:Z3187802|Vishnnu Shanmugam]] 23:46, 10 October 2009 (EST) Okies, all done. I'm going to review all my images and add summaries to them. Dr. Hill asked for a concise version to all the changes we make from the peer review process. I suggest everyone add their changes to the list I have started above and place your signature next to it.

--[[User:Z3186093|Jenny Guy]] 14:29, 10 October 2009 (EST)Hey vishnuu, i was thinking could you please alter
* the gaps between the spina bifida images (format this somehow with the images on the side and text on the other)
* the gap under "Brachydactylia & Acheiropodia"...maybe you have entered down too much????
cheers :)

--[[User:Z3187802|Vishnnu Shanmugam]] 21:27, 9 October 2009 (EST)Hey all. I have removed the newspaper image of rabbit (Due to copyright issues), and have replaced it with a series of images that guides the reader through the process of cloning a rabbit. I have NOT altered the text summarizing the creation of transgenic and clone rabbits as there are very important & detailed information which if removed puts complex processes in danger of oversimplification. I also corrected spelling mistakes in some images.

--[[User:Z3187802|Vishnnu Shanmugam]] 20:22, 7 October 2009 (EST) Hey gang. By popular demand (or the stress of reading) people want less text. I have removed the entire cleft palate & cleft lip section from abnormal development. For current research, I have also created a step by step picture guide for transgenic rabbit creation. It was initially meant to be a video, but this wiki page does not display (.gif) or (.mov) files. Sum, I remember that you did your references after me...so when I removed the cleft palate & cleft lip section, the references changed....so I have also adjusted your references accordingly. I don't think it is necessary to make all the changes outlined below as most comments are subjective (different people have different preferences) and seems like some comments were made because people had nothing else to propose.

--[[User:Z3126328|Jin Lee]] 10:01, 8 October 2009 (EST)Hi Guys, I have fixed spelling mistake and some people commented to make table form for advantages and disvantages section. But I liked the way I presented so I will leave in point form.

--[[User:Z3186093|Jenny Guy]] 14:32, 8 October 2009 (EST)
Hey! I looked at what i could change in the genetics section and decided to format a little. Our peers asked:
* genome information into a table - this is a little silly since there'd only be one column.
* Reformating in sections such as hitory and genetics. - have tried to do a little.
* Make pictures appear on the same side of page. maybe aligning the pics on either the left or right side instead of both left and right, and possibly putting them as thumbnails could also work. - i tried to put both of the chromosome images ont he same side (tried both left and right) but found that it looked terrible considering the size (which is needed to see it) as the text wouldnt fit around it very well.
* it will look much better if there is some work to be done for the structure of it especially the paragraph under the heading of 'abnormalities'. - am still in the process. not sure what else i can do since its in basic dot point form with not a large text to format. any ideas? or shall i leave it how it is now?
* maybe instead of writing the entire reference, you could just state The Broad Institute or just the people related to it - i feel that the entire team needs a mention since all people relate to it. noting just the broad institute is almost like noting a team of people here in unsw as just plainly "UNSW" which is just disrespectful.

==Things to work on noted by peers==

Hey, So the changes i will make will be in the introduction section. Also a lot of people have said to add pictures in the stages section to make it more interesting. I couldnt get permission to use the images so i bought tracing paper today! lol will try to draw them and see if they are ok enough to add. I think i am going to leave the timeline section as is because most people liked it. What do u guys think? --[[User:Z3185685|Sumaiya Rahman]] 15:31, 8 October 2009 (EST)

Sounds great Sum....Its gonna take some effort to trace it then scan it. GL --[[User:Z3187802|Vishnnu Shanmugam]] 21:37, 9 October 2009 (EST)

Hey guys,
I read through all the notes our peers have given us and summarised them into the following sections. Majority of them overlap (where ive put a new persons opinions in the same dot point over and over to stress the point on how many people noticed). Some things are easily changed, most of all i reckon its
# formatting
# pictures
# text to be more concise
So we just need to finalise all these minor things to improve our project. Please detail any changes you've made in the the heading above.
Cheers, --[[User:Z3186093|Jenny Guy]] 20:30, 7 October 2009 (EST)

INTRODUCTION
* a little too brief, more information needed
* For the first sentence (the characteristics that make the rabbit an excellent model for study), mention the section 'Why are we using rabbits?' under History section.
* For the second sentence (study that developed and improved micromanipulation techniques), mention the 'Transgenic Rabbit' section below under the genetics section. I've read the entire project page, and the introduction was the only place I found that was not precise enough (which is a great thing). These are minor things, but I think they will help with improving your project page.
*suggestion: Place the history section after the Introduction. This gives the viewer an overview of the use of the rabbit embryo. This way the viewer is first subjected to a few examples of the rabbit embryos use. It also allows him/her to understand where the rabbit embryo sits in with history. I guess this is a matter of personal preference.

HISTORY
* The advantages and Disadvantages would be better in a table. the history you might want to put the advantages and disadvantages into a table to make the page look a bit more tidy and easier to read when we go through it.
* The usage of rabbits for experimental models in science and medicine could be stated under the history section to allow background information for the readers to become aware of the topic and why the rabbit have been used to study specfic medical procedures and diseases.
* Spelling mistake under 'Discovery of Graafian Follicle', 2nd paragraph. I think it's previous instead of 'previcous'.
* Reformating in sections such as hitory and genetics. Make pictures appear on the same side of page.
* The history section can be improved if the infomation is expanded to give some more detailed background knowledge although i like the idea that the information is concise describing each scientists contribution towards the model.
* could be formatted to make the information stand out and a lot more appealing, I would recommend including pictures if possible that link to the text and making the advantages and disadvantages into a table rather than listing it.

TIMELINE
* more images to wholly understand. timeline/staging section was clear and concise, however it could be improved by adding more colour/pictures to maintain the readers' interest. The timeline and staging bits are very well written and clear but i think you should add a few images in there to match up with the text. Perhaps some pictures of embryos throughout development. Pictures for every stage would make it more visually attractive rather than just reading text. lack of pics in the timeline.
* It’s a little confusing that the development jumps back and forth according to the body part developing. Maybe it should be categorised according to time of development instead for greater clarity at first glance
* The timeline is just a little confusing, as its divided into development of different parts, which breaks the time flow.
* some of the information for the timeline section was too heavy for the page - would recommend only using some of the information on your actual page and having the rest as links to separate pages

STAGING
* pictures for stages would have been nice, unless there were none????
* a more even distribution of information, particularly more detail in the stages
* Provide pictures for individual stages. Get visual, and make the stages interesting to read. include pictures in the stages section.
* Staging section is also very well presented but the information presented in a table would even look better if there is use of some pictures to make it more interesting for its audience.
* staging section was very bland and would be more appealing with pictures. I dont think its necessary to cite your entire reference within the text

GENETICS
* genome information into a table
* Reformating in sections such as hitory and genetics.
* Make pictures appear on the same side of page. maybe aligning the pics on either the left or right side instead of both left and right, and possibly putting them as thumbnails could also work.
* it will look much better if there is some work to be done for the structure of it especially the paragraph under the heading of 'abnormalities'.
* maybe instead of writing the entire reference, you could just state The Broad Institute or just the people related to it

ABNORMAL DEVELOPMENT
* There is also a lot of content which might be alleviated by reducing the section on abnormal development. Too much information about the abnormalities. make more concise.
* the abnormalities went a bit over board, and didn't need that much attention I think (as compared witht the research which was good)
* reduce the writing content. for example. In the current research section, you have two scientific process of transgenic rabbits as well as cloning which is described in how these are done. why not draw a step by step diagram, and put these written steps in the link to the image.
* The information provided under Hydrocephalus and Brachydactylia was informative and interesting, but it contained too much text. I suggest you narrow it down and make use of Dots point, numbering, bold/italic words, and/or sub-sub-headings.
* Section for "Abnormal Development" gives the readers useful amount of information but i think its very lenghty, use of dot points can make it look even better and easy to understand.

CURRENT RESEARCH
* the group makes good usage of diagrams but towards the end diagrams die out, you might want to make the current research part of your assignment into diagrams and steps as there is just a bunch of information thrown there and alot of reading needed, if you put it into steps or diagrams it will make the marking process and reading process easier and allow us as reader to understand the information with ease.
* 'Transgenic Rabbit' should be shifted toward the genetic information on the rabbit. (Jenny - i dont agree with this as its research, not its offical genetics. Vishnnu - Neither do I)
* information in regard to stem cells should be brief and truncated. Example in regard to stem cell research should have brief and simple model explaining the process and why it used.
* There is too much information under stem cells. There is 2 examples of studies dealing with stem cells. A suggestion would be to just have one, and have a link saying 'Koga's research on Stem Cells'.
* Have the section 'links to Research labs and researchers' placed at the end of current research. That way, the information on the page will flow smoother.
* more of a focus on current research i.e. what each method is being used for and less on the process behind each method.
* great amount of information but in my perspective replacing the paragraphs with some dot points with heading and subheadings would further enrich understanding of readers.

OVERALL
* "As you start going down the page though the information starts to read a bit haphazardly, for example the developing body; jumping for section to section and the timeline section. it would be great if you could clean this up as it doesn't really flow." - formatting
* condense long slabs of text as the page is long
* format it so there are no huge gaps
* move the links to current research labs up closer to the current research section, just to keep it all together

==Constructive Criticism of Coordinator==
--[[User:S8600021|Mark Hill]] 08:07, 8 October 2009 (EST) The following comments are general in nature in no specific order, as it would be inappropriate to suggest specific changes and then assess the final project. Comments will be added during this week and you still have one week before final submission.

* There is no concise list of changes made to your project on the basis of peer assessments.
* Timeline of Embryo Development early stages, are in the introductory text said to be in hours, but it would be good to see it in the list as well.
* [[:File:Sizes.JPG]] Relative sizes, but no absolute size or scale given.
* A general comment about images. When you click an image and it opens, the information below the image should have an explanation of what the image shows, a reference (if from a paper) and a link to the original source (if available) as well as copyright information.
* Did you actually read the terms of use for this image that you cut n pated into the image description? [[:File:Rabbit_hybrid.jpg]] "For this purpose alone you may retrieve and display the Content on a computer screen. You may also print out, but not photocopy, one copy of individual files on paper and store files in electronic form on disc, but not on any server or any other storage device connected to a network where the Content could be accessed by other users." It clearly states that you cannot use this image online.
* Chromosomes section, images have no legends and structure not clearly organised.
* There needs to be better checking of your spelling and grammar, for example [[:File:Rabbitmalformation3.jpg]] "Plant Patkology of Tke Rockefeller Institute for Medical Researck", these mistakes while not major, suggests a lack of reviewing of your work by the group.
* Just a comment on project "feel", when several people work together on a project and insert their parts, the final project sometimes has an uneven style. Now that you have time to tidy up, try and get a common appearance throughout your project.

==Constructive Criticism of Peers==

--[[User:Z3218657|Sally Clarke]] 09:32, 1 October 2009 (EST)
Nice work Guys!
- Fantastic images used throughout - maybe a few more in the timeline so we can understand what is going on
- As you start going down the page though the information starts to read a bit haphazardly, for example the developing body; jumping for section to section and the timeline section. it would be great if you could clean this up as it doesn't really flow.
- The section on the abnormal development is great.
- The page is quite long - Maybe you could condense some of the text as it is kind of slab like
- i really enjoyed the breeding section
- The advantages and Disadvantages would be better in a table.

--[[User:Z3223194|Bronwyn Lewis-Jones]] 08:08, 1 October 2009 (EST) Hi Group 1! This is obviously a well organised and well researched assignment. I found it very informative. There are (of course) some things I feel could improve the overall submission. I loved that the timeline/staging section was clear and concise, however I think it could be improved by adding more colour/pictures to maintain the readers' interest. There is also a lot of content which might be alleviated by reducing the section on abnormal development. Hope this helps :)

--[[User:Z3218146|Julianna Lam]] 01:11, 1 October 2009 (EST) good job guys.
-Theres alot of relevant information.
-The timeline and staging bits are very well written and clear but i think you should add a few images in there to match up with the text.
-The image for the genetics bit is awesome.
-The page is nicely set out.
-Too much information about the abnormalities.

--[[User:Z3258567|Sando Rashed]] 20:04, 30 September 2009 (EST)hey guys, your page looks good, starts off well as there is not a bunch of information just thrown in, the information used is well thought, with the history you might want to put the advantages and disadvantages into a table to make the page look a bit more tidy and easier to read when we go through it (you can also do this with the info under genome), the group makes good usage of diagrams but towards the end diagrams die out, you might want to make the current research part of your assignment into diagrams and steps as there is just a bunch of information thrown there and alot of reading needed, if you put it into steps or diagrams it will make the marking process and reading process easier and allow us as reader to understand the information with ease, other than that the page looks quite good, well done on all your contributions

--[[User:Z3218792|Gabriela Pinget]] 21:51, 29 September 2009 (EST)

Nice page. I particularly liked the idea of lists of what is to come before each flood of information as was done with the ‘history of model use’ section.

- Nice easing into the topic with ‘advantages’ and ‘disadvantages’ lists.

- I liked the of rabbit embryo development to that of humans- puts it into perspective

- Good glossary- informative but not over- the- top

- Nice genetics section! Easy to read and a great use of illustrations to break up the information

- I also like that you took a page out of Mark’s book in the addition of the abnormalities section

Improvements:

- Perhaps some pictures of embryos throughout development.

- It’s a little confusing that the development jumps back and forth according to the body part developing. Maybe it should be categorised according to time of development instead for greater clarity at first glance

--[[User:Z3295026|Joe Nassif]] 17:01, 29 September 2009 (EST)

Your assessment has come along great in regard to the criteria format. There are a few alterations that could improve your project, the following alterations may enhance your wiki page:

'''-''' The usage of rabbits for experimental models in both science and medicine could be state under the history section to allow background information for the readers to become aware of the topic and why the rabbit have been used to study specfic medical procedures and diseases.

'''-''' Secondly the information on 'Transgenic Rabbit' should be shifted toward the genetic information on the rabbit. So far the project is looking and coming along great except for minor edits.

'''-''' Background information should be placed subsequent to the introduction allowing the reader to understand why this specific animal is used for specfic purposes.

'''-''' Figures/Graphs and the illustration of the anatomy and genetic development of the embryo were useful and clear allowing the viwers to understand and learn through the demonstration of pictures which were extremely informative.

'''-''' Genetics: the Genetics and Abnormalities information was great and very informative. It was great how the group compared the embryo with the human chromosome allowing the audience to understand the difference between both.

'''-''' Abnormalities: Information and details which were in the genetic section provided informative and interesting information, and it could be truncated a bit, additionally just discussing the chromosome development of the rabbit.

'''-''' Current Embryology Research: information in regard to stem cells should be brief and truncated. Example in regard to stem cell research should have brief and simple model explaining the process and why it used.

'''-''' Consequently, I thought the project was good it flowed and was very informative. The information was detailed, and the illustrations were useful and allowed the readers to gain a brief overview on the topic and it usage in history and in current research. Overall group 1 seem to achieve the critriea outcomes and summarised the topic really well, the comparsion to human embryo development througout the text was great and is a good referencing point in comparsion to the species choosen.
Great job --[[User:Z3295026|Joe Nassif]] 17:01, 29 September 2009 (EST)

--[[User:Z3255007|Sadaf Masood]] 12:09, 30 September 2009 (EST)Hello Group 1! Congrats on your awesome group project! I must say im very impressed with all the information you have posted and i have listed down the good bits and the bits that need to be improved. Since i am posting this a lil late, i have seen that u have already improved your project and few aspects...Good Job guys!

1. Very brief introduction...maybe just a little bit more info will be perfect

2. Abnormalities section is very informative and well researched, but very long, how about making it a little more precise?

3. The Advantages and Disadvantages of the using Rabbit is just simply perfect

4. The timeline is just a little confusing, as its divided into development of different parts, which breaks the time flow.

5. Pictures for every stage would make it more visually attractive rather than just reading text

6. Great Glossary!

There were few things earlier that need to be improved but you guys fixed it as soon as comments were posted so basically you guys rock :)An excellent effort guys. Best Wishes

# --[[User:Z3217015|Mitchell Mathieson]] 09:45, 25 September 2009 (EST)Very nice. The information was maybe a bit spread out, with heaps of gaps everywhere (formatting???), but the information was there, and relevant, and easy to read. I like how there was tonnes of information on current research, as I think that was the main aim, but the abnormalities went a bit over board, and didn't need that much attention I think. pictures for stages would have been nice, unless there were none???? The references are top notch, and the glossary is pretty amazing, and in the right place. Overall very good, I think formatting was the major downfall though, as it makes the page that much longer, and hence a little bit more difficult to read.

--[[User:Z3224449|Elide Newton]] 14:12, 26 September 2009 (EST)
HEllO GROUP 1: Well done on such a great assignemnt, looks like you have all worked very hard. Well my one point of constructive criticism would be to reduce the writing content. for example. In the current research section, you have two scientific process of transgenic rabbits as well as cloning which is described in how these are done. why not draw a step by step diagram, and put these written steps in the link to the image. that way it is more visual, the info is still there under the image link, and the page wont look as daunting to read. :) hope this helps!

--[[User:Z3254857|Begum Sonmez]] 00:46, 26 September 2009 (EST)
Hello Group 1. Firstly, I would like to let you all know that you have all done a great job. I'm impressed. I have a few suggestions that I think mite help to improve the page even more:

*Introduction:

1)For the first sentence (the characteristics that make the rabbit an excellent model for study), mention the section 'Why are we using rabbits?' under History section.

2)For the second sentence (study that developed and improved micromanipulation techniques), mention the 'Transgenic Rabbit' section below under the genetics section. I've read the entire project page, and the introduction was the only place I found that was not precise enough (which is a great thing). These are minor things, but I think they will help with improving your project page.

3)Breeding information was informative.

4) A suggestion: Place the history section after the Introduction. This gives the viewer an overview of the use of the rabbit embryo. This way the viewer is first subjected to a few examples of the rabbit embryos use. It also allows him/her to understand where the rabbit embryo sits in with history. I guess this is a matter of personal preference.

*Timeline:

1)Graphs, and the illustration of the zona pellucida and mucin coat were very clear and informative.

*Staging: I had no problems with it. The lack of information I think was a plus. It touched on the content in the Timeline section.

*History:

1) I loved the idea of the 'Disadvantages' of the rabbit embryo, it seemed unbiased. The brief timeline provided a clear and short summary.

2) Spelling mistake under 'Discovery of Graafian Follicle', 2nd paragraph. I think it's previous instead of 'previcous'. Also, the 2nd paragraph under this heading does not flow that well. Try rephrasing the 2nd sentence.

*Genetics:

The Genetics and Abnormalities section flow into eachother very well. I appreciated the comparison of the rabbit chromosome to the human chromosome.

*Abnormalities:

1) The information provided under Hydrocephalus and Brachydactylia was informative and interesting, but it contained too much text. I suggest you narrow it down and make use of Dots point, numbering, bold/italic words, and/or sub-sub-headings.

*Current Embryology Research:
1) There is too much information under stem cells. There is 2 examples of studies dealing with stem cells. A suggestion would be to just have one, and have a link saying 'Koga's research on Stem Cells'.

2) Have the section 'links to Research labs and researchers' placed at the end of current research. That way, the information on the page will flow smoother.

Overall, I thought there was a consistent structure in each section. The information was informative, and the pictures were relevant and helped me better understand the topics of discussion.

--[[User:Z3252340|Emily Wong]] 10:58, 27 September 2009 (EST) Firstly, great work. It is a well researched, structured and organised page. The content is very in depth and includes information on all of the specified areas. It is well referenced, with an extensive reference list indicating the amount of research put into the page. Some areas are more detailed than others. For example, the staging section is quite short and concise where as the Abnormal development section is extremely long considering it is not a needed topic. There is moderate use of pictures and diagrams, but more use could benefit the page as it may be able to negate some of the large slabs of text. The comparisons made between the human and the rabbit embryos are a good part of the project page. Each member of the group has contributed to the page and provided a lot of information on the section of content they were working on. What would improve this project is a more even distribution of information, particularly more detail in the stages, a few more diagrams or pictures to negate some of the text presented, more of a focus on current research i.e. what each method is being used for and less on the process behind each method.

--[[User:Z3126345|Gang Liu]] 14:26, 27 September 2009 (EST)In my opionion, this is a well constructed page. It includes major subheadings such as history, timeline, stages, genetics and current research. It is very concise and straightforward, which makes it easy to read. For example, a short introduction paragraph,"...the rabbit is an appropriate animal model as the results from many experiments are significant to that of other mammals, including humans.", explains to reader why rabbit is such a suitable model.

It also provides a logic flow. For example, in history of rabbit model use section, it has provided advangtages and disadvantages of model use. This is appropriate, as it demonstrates the significance of rabbit model use in scitific discovery. In addition, it has provided detailed background information for each discovery. This makes it interesting to read.

It is also important to compare development of embryo between rabbit and human. For example, "... the similarities of this developmental pattern in humans and rabbits, suggests that the same growth increment is required to achieve the same stage. The main difference observed between human rabbit gestational duration is due to the fetal growth phase...", this has suggested human and rabbit share many similarities. Not only this page has demonstrated detailed written information of timeline development, it also provided graphics to reinforce the concept. For example, the hand drawing of developing embryo. As well as the comparison between human embryo and rabbit embryo timeline development.

It is also interesting to learn that rabbits have 22 pairs of chromosome, whereas humans have 23 pairs of chromosome.

Sections such as abnormal development and current research have demonstrated extended research and understanding. For example, hydrocephalus, spina Bifida, stem cell research and cloning techniques. All of these have showed the in depth research in textbooks, journals and internet based literatures.

However, this page can be improved by considering the following points.

*Provide pictures for individual stages. Get visual, and make the stages interesting to read.

*Reformating in sections such as hitory and genetics. Make pictures appear on the same side of page.

*Typo: "A rabbits potential for reproduction..."

*Sections such as abnormal development and current research are too lengthy. Might consider shrink the content.

*Lack of glossary.

Overall, big thumbs up!

--[[User:Z3252231|Angama Yaquobi]] 01:12, 28 September 2009 (EST)
First of all i would like to congratulate all the team members for a great team work.
Well done guys!! The group project looks amazing, the information presented is very concise
and straight to the point which makes it very easy for the readers to grab
the important information that they need to enhance their knowledge.
I like the section of history, the information is very clear,
and i like the idea of providing some background knowledge to the readers
about the disadvantages of the use of rabbit.
The history section can be improved if the infomation is expanded
to give some more detailed background knowledge althought
i like the idea that the information is concise describing each
scientists contribution towards the model.
The section for timeline is impressive, in my perspective its a great idea to cover alot of content in a very smart way
which is by the use of subheadings to make it easy to understand for audience.
Staging section is also very well presented but the information presented
in a table would even look better if there is use of some pictures
to make it more interesting for its audience. Genetics section
is beautifully presented, all the information is there with some
amazing pictures but will look much better if there is some work to
be done for the structure of it especially the paragraph under the
heading of 'abnormalities'. Section for "Abnormal Development" gives
the readers useful amount of information but i think its very lenghty,
use of dot points can make it look even better and easy to understand.
The same for Current embryology research, great amount of information but
in my perspective replacing the paragraphs with some dot points with
heading and subheadings would further enrich understanding of readers.
Also glossary would complement the webpage. But overall,
great amount of information which shows alot of research
which has been done by all the team members. Well done guys!!

--[[User:Z3217686|Thomas Dangerfield]] 13:29, 28 September 2009 (EST) Hey guys! Good work on your assignment! Plenty of info which is good, and very well referenced. The glossary is a good idea too! I do agree with a few others about the lots of clear spaces in the formatting, and the lack of pics in the timeline though. Also under the genetics section, maybe aligning the pics on either the left or right side instead of both left and right, and possibly putting them as thumbnails could also work. In the abnormalities section, there might have been a little too much info that probably wasn't needed, but i do like the effort put in. Over all, possibly more time spent on formatting and determining which sections are more important and which sections may need to be limited. Other than those points, the whole assignment seemed very well done!

--[[User:Z3215682|Carly Mooney]] 11:32, 29 September 2009 (EST)
You assignment is visually appealing and the genetic information e.g. the number of chromosomes of a rabbit was very interesting.There are some additional sections you have added which really complement your assignment e.g the abnormalities and I really liked the advantages and disadvantages of using the rabbit model. The few suggestions I would make is to:
* include pictures in the stages section
*place the pictures throughout the text (e.g. to left or right). You did this up until abnormalities and I felt it broke the flow of the written text.
* and maybe move the links to current research labs up closer to the current research section, just to keep it all together.
Overall very impressive though.

--[[User:Z3220040|Joanne Raffel]] 15:25, 29 September 2009 (EST) Nice wikipage, the page looked interesting however I agree with some others that the formatting of the page was inconsistent. I thought the referencing was great but found it a bit confusing with the reference numbers after the paragraphs. I thought the subheadings werent distinct enough, especially in relation to the text, which made it difficult to read. The history section could be formatted to make the information stand out and a lot more appealing, I would recommend including pictures if possible that link to the text and making the advantages and disadvantages into a table rather than listing it. I especially liked the comparison between the rabbit and the human embryo, however some of the information for the timeline section was too heavy for the page, I would recommend only using some of the information on your actual page and having the rest as links to separate pages. The staging section was very bland and would be more appealing with pictures. I dont think its necessary to cite your entire reference within the text, especially in the genetics section, maybe instead of writing the entire reference, you could just state The Broad Institute or just the people related to it. The abnormalities section was a good inclusion however it was very extensive, along with the current research section. Overall a very good wikipage.

----
*Hey, Well done guys!!! I think our group worked pretty well! I think we communicated each other well and did very best for their section. I fixed my spelling mistake and problem with sentence! As Begum mentioned, I think placing the history part after the introduction is better idea. --[[User:Z3126328|Jin Lee]] 13:36, 26 September 2009 (EST)

*Hey guys,
the project has come together brilliantly! it looks quite good. Hopefully mark will like it! ill add some terms to the glossary and try do some formatting (the first image is a little too big i think!) --[[User:Z3186093|Jenny Guy]] 10:28, 24 September 2009 (EST)

Hey. Yep all good. I had to get rid of the pics, so stages table is now blank. Im pretty much done. I'll see what i can add to the glossary. thanks :)--[[User:Z3185685|Sumaiya Rahman]] 23:34, 23 September 2009 (EST)

Hey all, I'm going to start a glossary and add it under the reference section. Scan your text and add to the glossary in alphabetical order. Also under the marking criteria, it says to provide links to researchers and research laboratories.....i'll start that under the glossary. Everyone else OK with their stuff?--[[User:Z3187802|Vishnnu Shanmugam]] 23:08, 23 September 2009 (EST)

Hey Sum, The images look fine but I don't think you can use the images like that since the journal KARGER is being particular about its copyright laws. I tried tracing around the images but it does not seem to resemble anything like an embryo. I did however find this link...go to it and scroll down to the images of the developing embryo. You might be able to edit it to resemble rabbit embryo. --[[User:Z3187802|Vishnnu Shanmugam]] 15:10, 23 September 2009 (EST). To get to the link, Google image search "rabbit gestation"....click on the "rabbit,gestation age" image from nature.com
Also google image search "The Haeckel embryo sequence"...could be useful after some editing

oh my god!! I summarised all of my research and wrote down on the page. Then I blew up everything!!!
it says 'edit conflict' what da?? I lost all of my work...it was my stupid mistake...--[[User:Z3126328|Jin Lee]] 01:06, 23 September 2009 (EST)

Oh also.. let me know if the images look stupid --[[User:Z3185685|Sumaiya Rahman]] 00:34, 23 September 2009 (EST)

Hey thanks vishnuu. I put some images up in the stages table. I did edit the pictures, but im not sure if im allowed to use it like this? have a look and let me know. Also im not sure what is going on with the reference section seems kinda all over the place, so i havnt added mine in yet. Maybe we should fix that up somehow? :) oh LOL about the breeding rabbits bit! haha
--[[User:Z3185685|Sumaiya Rahman]] 00:31, 23 September 2009 (EST)

Hey Sum, Sorry for the late reply. For $330, I'd rather breed rabbits and take the photos myself. I had a look at the original images, what we can do is trace around the developing rabbit embryo using the pencil tool on an image editing software(eg. microsoft paint - already preloaded into most windows). Then upload the image to the assignment. Does your PC have adobe fireworks?...extremely good for tracing images. If not, have a go at it with microsoft paint....I shall also have a go at it, then I shall let you know on this discussion page at about 3PM t'morrow. If any good then I'll send it to your student email. If not, we discuss potential alternatives. good luck Sum! --[[User:Z3187802|Vishnnu Shanmugam]] 23:51, 22 September 2009 (EST)

Yep thats the article i used for the developmental stages and put in a table. I should have my timeline posted by end of today. I also couldn't get permission to use the pictures as they wanted about $330 for me to use it!! no thanks. I'll see if i can work it in somehow. Vishnuu did u have any ideas on editing the images?? --[[User:Z3185685|Sumaiya Rahman]] 12:29, 22 September 2009 (EST)

Have a look at this article, it's helpful for comparison bt rabbit and human in developmental stages!--[[User:Z3126328|Jin Lee]] 13:35, 21 September 2009 (EST)
*Sampled rabbit embryos were staged using the Carnegie criteria, in order first to determine if they were consistent with the rabbit developmental pattern, and second to compare this pattern with the human one. Our results show a suitable '''comparison of rabbits and humans in early developmental stages''', except for the neural growth.
[http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowAbstract&ArtikelNr=73136&Ausgabe=229537&ProduktNr=224239
]

Absolutely correct Juliana, my research articles and their links are labelled 1-6 so far, the rest is yours..... I'll fix it for you. A timeline image seems tricky and i'm unsure, send Dr. Hill an email on m.hill@unsw.edu.au and see what he says. We still have till thursday to finish everything, so don't be too worried....try to finish all your other stuff and leave the drawing of the timeline last.--[[User:Z3187802|Vishnnu Shanmugam]] 17:49, 20 September 2009 (EST)

*no.1-7 in reference section is mine. and I think links under Vishnnu's research on the discussion board is mine. let me know please. (I can't remember all of my researches)
I want to make a timeline image but I can't do it;;; I asked Mark few weeks ago but havn't replied yet....can somebody help me???--[[User:Z3126328|Jin Lee]] 17:26, 20 September 2009 (EST)

'''** Hey Jenny, dont worry!! the project is not due until next week! (24th) we will have it done by then!! I am still waiting for permission to use the pictures in my stages section, thats why it hasnt been done yet. Hopefully i can get permission, otherwise i'll have to draw them (or something) myself.''' --[[User:Z3185685|Sumaiya Rahman]] 14:03, 17 September 2009 (EST)

It says project due date 24th september.......if the due date had been brought forward why was it not posted on the project main page? --[[User:Z3187802|Vishnnu Shanmugam]] 13:48, 17 September 2009 (EST)

EVERYONE...WHY IS THE REST OF OUR PROJECT NOT DONE??
* vishnuu...its due TODAY!! how can you post things up next Monday? Please make sure youve referenced EVERY image and all text (i know youve said you need to do this...but its easiest done when writing the section as now you have to go back and find everything, insert numbers etc. Remember to put the reference in the reference section. For the current research section i thought this might help you (as during my lecture in another class they spoke about how rabbits are used in heart development. Is there anything that you've found to include this?). Also I found this website during my research so it may help you? [http://www.evergen.com/rabbit_experience.html/ Rabbit Experiments]
* sum - where is the timeline???? It doesn't exist? Where is it? Also, we need some sort of visual for the staging. Have you found an images? Could you draw the stages of embryo development? It just looks incredibly boring.
* julianna...you need to put up more other than just two historians...there is NO referencing whatsoever in your entire section. where have you found this information? have you put it in your own words or copied it? You need to add some more refences to the reference section at the bottom..there just aren't many to back up your research.

seriously guys. ive added photos and tried to spice up the project but i am NOT going to finish your sections for you. ITS DUE IN 3 HRS! i cant believe you guys haven't bothered to even try finish this. Im very disappointed and i think its slack to let the team down. --[[User:Z3186093|Jenny Guy]] 10:34, 17 September 2009 (EST)

----

Hey all, just need to finish editing the current research part before i post it up, also need to edit some of my images under abnormal development and also references. Should be all done by Monday. --[[User:Z3187802|Vishnnu Shanmugam]] 07:02, 17 September 2009 (EST)

--[[User:S8600021|Mark Hill]] 01:40, 8 September 2009 (EST) OK guys, this is still just a page of text......

--[[User:Z3126328|Jin Lee]] 14:50, 3 September 2009 (EST) I want to make a timeline?

--[[User:S8600021|Mark Hill]] 08:42, 21 August 2009 (EST) z3187802 has contacted me and has been away sick. He should still complete his components of the group project.

Our group is Sum, Vishnnu, Juliana and Jenny. Today in the lab we have decided to research the RABBIT! [http://embryology.med.unsw.edu.au/OtherEmb/Rabbit.htm/ Rabbit embryology from Mark Hill]

(Juliana's email belebele85@msn.com)

----
This is apparently what we need to include in our case study:
#Timeline of Embryo Development - how long (SUM)
#Staging - are there species specific staging, what occurs when (SUM)
#History of Model Use - when was it first used, (JULIANNA)
#Genetics - chromosome number, sequencing (JENNY)
#Abnormal Development (VISHNNU)
#Current Embryology Research - research papers and findings (VISHNNU)

Hey guys, maybe we should add a section comparing rabbit to human development
--[[User:Z3185685|Sumaiya Rahman]] 16:45, 6 August 2009 (EST)

That sounds like a good idea Sum....seeing that human development is the primary theme of the course, not including it would be criminal!. -vishnnu

Report:
* Links to resources and discussions are to be posted on the group talk page, the project page is for the actual assignment
* Final assignment will be marked by another group and everyone will be given a marking criteria
* No information should be obtained from Wikipedia and all information (tables & graphs included) must be referenced
* Please feel free to suggest any further topics which can be included

== Research: ==
So i think the main rabbit used in research is the oryctolagus cuniculus. Lets focus mostly on that (or at least i, Jenny, will since im going genetics). This link is great for the specific genetics: [http://www.ncbi.nlm.nih.gov/nuccore/AJ001588/ Oryctolagus cuniculus complete mitochondrial genome]

Here's some stuff about benefits of modeling from a textbook. I haven't yet written as my own so its still the authors material. Just thought it might benefit us all (and raise our morale as we thought the rabbit might suck..but it doesn't!) We're not "submitting" this as our own work so technically we're not yet copyrighting their material.
Ive cited the book here and the website i got it from:
[http://books.google.com.au/books?id=RY0rXE2HgqsC&pg=PA344&lpg=PA344&dq=rabbit+embryology+genetics&source=bl&ots=rbr3CuBRxY&sig=p8055w9oYQmsQeuN78mgXBGmRK4&hl=en&ei=NI2KStaQJIvSsQOEpMjEDQ&sa=X&oi=book_result&ct=result&resnum=3#v=onepage&q=&f=false/ Cibelli, J., Lanza, R., Campbell, K. and West, M. 2002. Principles of Cloning. Academic Press]

“Rabbits were one of the first species in which blastomere nuclear transfer succeeded; as a model species, rabbits placed a central role in developing the micromanipulation technologies in embryos.” Other advantages for using rabbits are:

# “The costs to animal procurement, animal care, and oocyte production in rabbits are relatively low compared to large animals.” e.g. a cow embryo is 30x more expensive that a rabbit embryo
# “The developmental biology of rabbit embryos and fetuses resembles more closely that of large farm animals than that of rodent model species, including the transition from maternal to embryonic control of embryo development.”
# “The pregnancy of rabbits is relatively short (1 month), allowing rapid evaluation of fetal and postnatal development. In comparison, the gestation length for cattle is 9x longer.”
# “The sizeable milk production of rabbits allows their use as test animals for therapeutic protein expression in milk, or as a living bioreactor.”
# “Rabbits are induced ovulators. Domesticated rabbits are nonseasonal breeders and produce multiple offspring in one litter. These reproductive patterns make the use of rabbits for reproductive research highly efficient.”

----
Here are some links i (sum) found which may help. Need to go through all the info and sort it out, But there are a couple of good diagrams.

'''Links for group assignment'''

http://www.reproduction-online.org/cgi/reprint/48/1/43

http://books.google.com/books?id=RY0rXE2HgqsC&pg=PA344&dq=rabbit+embryo+stages&as_brr=3#v=onepage&q=rabbit%20embryo%20stages&f=false - good for what studies in rabbit embryo have been used for. And has a good table for embryological stages!!

http://books.google.com/books?id=ljAKtC-iIrIC&pg=PA264&dq=rabbit+embryo+stages&as_brr=3#v=onepage&q=rabbit%20embryo%20stages&f=false

http://books.google.com/books?id=73bbKzqRvLsC&pg=PA156&dq=rabbit+embryo+stages&lr=&as_brr=3#v=onepage&q=rabbit%20embryo%20stages&f=false - picture of implantation

http://books.google.com/books?id=aZ7DQYFyxswC&pg=PA122&dq=%22rabbit+development+stages%22&lr=&as_brr=3#v=onepage&q=&f=false
-------
Hi I(Juliana) uploaded file, you guys can have a look.
Go to 'Upload File' tab and click ' early growth of rabbit trophoblast' file.

-------------
also I found an interesting article!
'''An Electron Microscope Study of the Embryology of the Intercalated Disc in the Heart of the Rabbit'''
Alan R. Muir
The Journal of Biophysical and Biochemical Cytology, Vol. 3, No. 2 (Mar. 25, 1957), pp. 193-202
Published by: The Rockefeller University Press

http://info.library.unsw.edu.au/cgi-bin/local/access/ej-access.cgi?url=http://links.jstor.org/sici?origin=sfx%3Asfx&sici=0095-9901(1957)3%3A2%3C193%3AAEMSOT%3E2.0.CO%3B2-S
--

[[User:Z3126328|Jin Lee]] 10:48, 25 August 2009 (EST)

----------------
I found helpful book in the library
'''Bensley's Practical Anatomy of the Rabbit 8thE by E.Horne Craigie, Toronto, University of Toronto Press 1948'''
--[[User:Z3126328|Jin Lee]] 13:27, 27 August 2009 (EST)

==Vishnnu's Research==

'''Background reading (Vishnnu)'''

Hey everyone. I'm starting my background reading section where I shall describe my research resources. They contain a summary and a link to the resource itself. I shall keep this "notes" section updated with each new entry I add.

'''Notes:'''

*Articles 1 & 2 - Juliana this could be useful to you.

*Article 2 - Sum this could be useful to you.

*Articles 3 & 4 - Abnormal development articles (added: 02/09/2009)

*Articles 5 & 6 - Abnormal development articles (added: 13/09/2009)

'''Article 1'''

'''The rabbit as a model for reproductive and developmental toxicity studies''' --[[User:Z3187802|Vishnnu Shanmugam]] 21:05, 30 August 2009 (EST)

''Robert H. Foote and Edward W. Carney'' ''Reproductive Toxicology 14 (2000) 477–493'' ''Department of Animal Science, Cornell University, 204 Morrison Hall, Ithaca, New York 14853-4801, USA Developmental and Reproductive Toxicology, ''The Dow Chemical Company Midland, Michigan 48674, USA''

'''Summary'''

This is a review article of a study looking at the use of rabbits in toxicological studies. The article describes the advantages in using the rabbit experimental model as opposed to the rodent model (mice & rats) and outlines the differences that make toxicological studies on rabbit embryos more accurate than rodents to resemble similar toxicological effects in human embryos. The article describes various techniques that can be used (eg. blood collection from marginal ear vein, artificial insemination, embryo collection) and solutions to some common problems that researchers face when using animal models. Very interesting article with a great quote from Robert Koch to open the eyes of researchers to other animal models:

“Gentlemen, never forget that mice are not human beings”

Want to find out more? Follow the link!

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6TC0-41SBGDH-1&_user=37161&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_acct=C000004218&_version=1&_urlVersion=0&_userid=37161&md5=4db60dc9352996fc4865b9d781b0128d

'''Article 2'''

'''Developmental stages in the rabbit embryo: guidelines to choose an appropriate experimental model''' --[[User:Z3187802|Vishnnu Shanmugam]] 21:05, 30 August 2009 (EST)

''S. Beaudoin; P. Barbet; F. Bargy''
''Fetal Diagnosis and Therapy; Nov/Dec 2003; 18, 6; Academic Research Library''
''pg. 422''

'''Summary'''

The article describes the various stages in the developing rabbit embryo and the rationale for using rabbits to study normal and abnormal embryology. The article details normal developments in the rabbit embryo and compares it to the developing human embryo. By making this comparison the article argues for the validity of rabbit embryology to better understand human embryology and also suggests that due to the similarities in the developing rabbit and human embryos, experiments on rabbit embryo’s yield more reliable results for human embryology. The article has some rare images on normally developing rabbits and breaks the developmental stages down (in days) describing the observable characteristics that form (eg. Limb development & body formation).
I have decided to use the image provided in the journal.

Definitely worth reading people, follow the link!

http://content.karger.com/produktedb/produkte.asp?typ=fulltext&file=FDT2003018006422

'''Article 3'''

'''Acheiropodia is caused by a genomic deletion in C7orf2, the human orthologue of the Lmbr1 gene''' --[[User:Z3187802|Vishnnu Shanmugam]] 04:32, 2 September 2009 (EST)

''P. Ianakiev, M. J. van Baren, M. J. Daly, S. P. A. Toledo, M. G. Cavalcanti, J. Correa Neto, E. Lemos Silveira, A. Freire-Maia, P. Heutink, M. W. Kilpatrick, P. Tsipouras''
''Am. J. Hum. Genet. 68:38–45, 2001''
''Department of Pediatrics, University of Connecticut Health Center, Farmington, CT;''
''Department of Clinical Genetics, Erasmus University, Rotterdam;''
''Whitehead Institute for Biomedical Research, Cambridge, MA;''
''LIM/25-D, University of Sao Paulo School of Medicine,''
''And Private Practice, Sao Paulo;''
''Private Practice, Porto Alegre, Brazil;''
''Department of Genetics, UNESP-Universidade Estadual Paulista, Botucatu SP, Brazil''

'''Summary'''

The article describes the developmental abnormality Acheiropodia can be passed down genetically from parent to offspring. Acheiropodia (also known as Horn Kolb Syndrome) is a condition where the distal extremities of the embryo fail to form. Although it is not fatal, the individual endures a very difficult life without hands and feet. The article notes that the disorder only affects the development of the limbs and has no other reported manifestations. The article defines this to be an autosomal recessive disorder which means that two copies of an abnormal gene must be present in the affected individual in order for the disease to develop. Thus, each parent passes an abnormal gene to the offspring. It is interesting to note the process of the malformation from genotype to phenotype: small deletions on the chromosomes produce abnormal genes, the abnormal genes are then passed down to the offspring, the offspring that inherits two of the abnormal genes is unable to code for the correct proteins and as a result, there is failure in normal development of limb extremities in the embryo phenotype. The article also has a shocking image of an individual with Acheiropodia which highlights the extent to which it can impact a person’s life and the urgent need to find a cure.

Read more about the exact nature of the abnormal gene using the link.

http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=1109034

'''Article 4'''

'''Epidemiology of congenital clefts of the lip and palate''' --[[User:Z3187802|Vishnnu Shanmugam]] 04:32, 2 September 2009 (EST)

''JOHN C. GREENE'' ''D.M.D. ,M.P.H.'' ''Public Health Rep. 1963 July; 78(7): 589–602''

'''Summary'''

This review article combines research to study the factors causing the developmental abnormalities cleft palate and cleft lip in populations. “Cleft palate (palatoschisis)” and “cleft lip (cheiloschisis)” are the terms used to describe the non- fusion of the upper lip, hard or soft palate and typically occur during the gestation phase of embryonic development. The article tables the occurrence of cleft palate and cleft lip in populations of people in various cities across the world. It also compares the occurrence of cleft palate and cleft lip in males and females. The article finds that the incidence of cleft palate and cleft lip is:

*Is random in males and females (ie. Occurs approximately evenly in both sexes)

*Is random in people living in different cities

*Is higher in children of mothers over the age of 35

*Is higher in white populations and lower in the negro populations which suggests possible role of environmental factors

*No concrete proof that cleft palate and cleft lip is hereditary

*Is higher in rats exposed to radiation and those fed riboflavin

*Is higher in rabbits and other lab animals exposed to higher stress through cortisone injections

Although the article is now quite ancient, it is interesting to note the incidence of cleft palate and cleft lip among people. It also shows the historical foundation of research into the causes of cleft palate and cleft lip through animal experimentation.

Read more about cleft palate epidemiology using the link.

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1915191

'''Article 5'''

'''Chromosome abnormalities in human embryos''' --[[User:Z3187802|Vishnnu Shanmugam]] 00:10, 13 September 2009 (EST)

''Santiago Munne & Jaques Cohen The Center for Reproductive Medicine and science of Saint Barnabas Medical Center, New Jersey, USA Human Reproductive Update 1998, Vol. 4, No. 6 pp. 842-855 European Society of Human Reproduction and Embryology''

'''Summary'''

As the title suggests, this article focuses on chromosomal abnormalities in the developing human embryo. To understand this article, it is necessary to first establish some basic definitions that are used throughout the article. Aneuploidy can be defined as the occurrence of one or more extra or missing chromosomes leading to an unbalanced chromosome number. Although most babies with an unbalanced amount of chromosomal material miscarry during the first trimester of pregnancy, those that are born have crippling conditions such as:

* Birth defects

* Turner's syndrome (disorder where a female child is born with only 1 X chromosome)

* Down's syndrome (disorder where child is born with 3 copies of chromosome 21)

* Edward's syndrome (disorder where child is born with 3 copies of chromosome 18)

* Patau's syndrome (disorder where child is born with 3 copies of chromosome 13)

* Klinefelter's syndrome (disorder where male child is born with 2 copies of the X chromosome and 1 Y chromosome)

Polyploidy is a type of aneuploidy where the baby has three, four, or more sets of chromosomes instead of the two present in diploids. Chromosomal mosaicism is when different cells within an individual, who has developed from a single fertilized egg, have a different chromosomal makeup. Most commonly there will be some cells with a typical number of chromosomes (46 chromosomes) and other cells with an altered number or structure of chromosomes.

The article explores the possible causes of chromosomal abnormalities resulting from pregnancy though techniques such as IVF (In-Vitro Fertilization) and ICSI (Intracytoplasmic Sperm Injection). It also analyses the role of FSH (follicle stimulation hormone), temperature, water and light in chromosomal abnormalities.

The article finds:

* High FSH concentration increases likelihood of chromosomal abnormalities

* ICSI & IVF techniques have increased likelihood of chromosomal abnormalities

* Chromosomes exhibit temperature sensitivity and changes in temperature can cause chromosomal abnormalities

Although the article makes a number of findings, it is yet to be backed up with convincing evidence; the article has some really cool images of the developing embryo soon after fertilization. Overall, an interesting read.

Interested? Follow the link!

http://humupd.oxfordjournals.org/cgi/reprint/4/6/842.pdf

'''Article 6'''

'''Evaluation of the Safety and Pharmacokinetics of the Multi-Targeted Receptor Tyrosine Kinase Inhibitor Sunitinib During Embryo–Fetal Development in Rats and Rabbits''' --[[User:Z3187802|Vishnnu Shanmugam]] 00:10, 13 September 2009 (EST)

''S. Patyna, J. Haznedar, D. Morris, K. Freshwater, G. Peng, J. Sukbuntherng, G. Chmielewski, and D. Matsumoto''
''Pfizer Global Research and Development, San Diego, California''
''Roche LLC, Palo Alto, California''
''Pfizer Global Research and Development, Kalamazoo, Michigan''
''Xenoport Inc., Santa Clara, California''
''Pfizer Global Research and Development,'' ''Groton, Connecticut '' ''Birth Defects Research (Part B) 86:204–213 (2009)''

'''Summary'''

The article looks at how toxicity affects embryo-fetal development. The article describes the abnormal changes that occur when Sunitinib (an oral inhibitor of multiple receptor tyrosine kinases) is administered to pregnant rabbits and rats. This experiment was performed in an attempt to mirror the effects of antiangiogenic agents used in cancer treatment. Sunitinib is an antiangiogenic agent and the use of antiangiogenic agents is not recommended for treating cancer in pregnant patients because of the potential harm to embryo-fetal development. Angiogenesis (the formation of blood vessels) plays a critical role in embryo–fetal development and antiangiogenic agents slow down and/or stop the formation of blood vessels in order to control cancer and stop its spread. In pregnant patients however, this has the potential to adversely affect the developing embryo and these adverse effects is what is investigated in this article.

The article finds the antiangiogenic agent Sunitinib at toxic levels can result in:

* Embryo death

* Fetal skeletal malformations including vertebrae malformation and cleft lip/palate

* Teratogenic effects in rabbits

* Decreased maternal and fetal body weight

This article is a recent study and provides important findings regarding the use of antiangiogenic agents, especially during pregnancy. Although the maternal effects are minimal, the adverse effects to the embryo are significant and permanent. The article makes good use of tables and graphs to juxtapose pieces of information and to show trends. It is very interesting to note the extent to which chemicals can impact the vulnerable developing embryo.

Read more at link. (Use institutional login from UNSW computers)

http://www3.interscience.wiley.com/journal/122262246/abstract?CRETRY=1&SRETRY=0

------
thank you so much Vishnuu~~^^ from Juliana
-----
I also changed the format if you guys dont mind--[[User:Z3126328|Jin Lee]] 18:33, 31 August 2009 (EST)
----

Hey '''Vishnuu''', that link you found with the stages is awesome! thanks so much. Do you know if i am allowed to use the embryo pics in that article on our wiki page?? i'm not sure about the copyright rules. It says at the bottom of the article "Reproduced with permission of the copyright owner. Further reproduction prohibited without permission."
Does this mean we can only provide a link to it on our page? if so that's a shame, because those pics were fantastic!! '''SUM'''

Oh i also added an introduction - sum

Hey Sum,
Unfortunately, since its copyright protected we can't use the image directly......but there is a way of getting around it....You can modify the image using picture editing tools, then simply reference where the original picture came from and state that it has been modified by you. Alternatively, you can trace around the picture and provide only an outline (this will be very difficult to do with detailed pictures, a good picture editing software is recommended). Either way according to whats written under '''editing basics''' we need to include a picture that has been drawn up ourselves in the project. Also, not sure if you are aware, but the project is NOT due on Thursday (3rd September), Dr. Hill has very generously given everyone an extension till after mid-session break. --[[User:Z3187802|Vishnnu Shanmugam]] 02:35, 2 September 2009 (EST)

==Julianna's Research==
[http://netvet.wustl.edu/species/rabbits/rabtmodl.txt]
HISTORY OF THE RABBIT (IN RESEARCH)

A. Discovered in Spain about 100 B.C.
B. Domesticated in the 1500's
C. Standardization of breeds in 1800's
1. Research Uses
a. 1852: Rabbits have DL-hyoscyamine
(a) Can survive belladonna
(b) Endogenous atropine esterase
b. 1884: Pasteur develops rabies vaccine
c. 1891: Heape performs embryo transfer
(a) Influence on phenotype of the
uterine environment
d. 1908: Ignatowsky produces atherosclerosis
(a) Fed diets of milk, meat, and
eggs
(b) Produced intimal lesions
(c) Believed lesions due to protein
e. 1928: Demonstrated intranuclear development
of herpes virus
f. Graafian follicle was first observed
g. Coat colors and Mendelian inheritance
h. Immunology studies
i. Testing of human use products
j. Basic science studies
k. Diagnostic requirements
l. Eye Research
m. Pyrogen testing
n. Fetal drug induced teratology
o. Parasite research

LITERATURE REVIEW OF RABBIT USE

A. 1956 to 1800 ... Over 8000 citations
B. 1966 to 1987 ... 130,000 citations linking the rabbit to
all areas of research
C. 1988 to present ... 821 citations under the search
criteria: Rabbit: Model: Human Disease
D. Numbers of Rabbits Used (APHIS; ILAR records 1989)

1967 504,500
1978 439,986
1982 547,312
1983 466,810
1984 529,101
1985 544,621
1986 521,773
1987 534,385

ADVANTAGES OF USING RABBITS
A. Provides repeatability of animal model studies
B. Large enough for single samples
C. Many stocks/strains as animal models
D. Easily managed
E. Quality of immunologic products
F. Ease of reproductive control

DISADVANTAGES OF USING RABBITS
A. Most colonies are a storehouse of diseases
B. Extremely variable to responses to general anesthetics

[http://www.ncbi.nlm.nih.gov/pubmed/18430597]
The rabbit as a model to study asthma and other lung diseases.Keir S, Page C.
Sackler Institute of Pulmonary Pharmacology, Division of Pharmaceutical Sciences, 5th Floor Hodgkin Building, King's College London, Guy's Campus, London SE1 9RT, UK.

No single animal model is able to reproduce all the features of human asthma. However, the similarities between neonatally immunised rabbits and human asthma highlight the value of this model in the investigation of asthma pathophysiology and in the development of therapeutic agents. Airway inflammation and airway responses to various stimuli including histamine, adenosine 5'monophosphte and antigen in allergic rabbits have shown similarities with the responses observed in asthmatics. Furthermore, functional studies in rabbit airways show they are poorly responsive to capsaicin as are human airways. Chronic pre-treatment with capsaicin desensitises the TRPV(1) receptor enabling studies into the effect of this drug in both rabbits and man. The allergic rabbit model has been used extensively in assessing the various classes of anti-asthma drugs and is sensitive to similar drugs as patients with asthma, including beta-adrenoceptor agonists, corticosteroids, phosphodiesterase inhibitors and theophylline. This article highlights the usefulness of the rabbit as a species to study lung biology.

[http://www.ncbi.nlm.nih.gov/pubmed/8447943]
Effects of strain and embryo transfer model (embryos from one versus two donor does/recipient) on results of cryopreservation in rabbit.Vicente JS, García-Ximénez F.
Departamento de Ciencia Animal, Universidad Politécnica de Valencia, Spain.

Differential effects of 2 transfer models for normal thawed embryos of 1 donor doe were studied on the offspring rate and their embryo survival at birth from 3 selected rabbit strains (SY and SB: synthetic strains, NZ: New Zealand White). Morulae were obtained 64-66 h post-coitum from 93 adult does treated with 25 IU of hCG (SY:36, NZ:27, SB:30). Morphologically normal morulae were frozen in the presence of 1.5M DMSO and stored in liquid nitrogen. Normal thawed embryos were transferred into the oviducts of synchronized recipient does of the same strain 48 h after being injected with 25 IU of hCG (SY:28, NZ:21, SB:24). Each recipient received embryos from 1 (single transfer) or 2 different donor does (double transfer). Significant differences were observed in the post-thawing percentage of normal embryos between strains (SY:95 +/- 1% and SB:85 +/- 3%, P < 0.05; NZ: ,91 +/- 2%). After transfer, no significant differences were observed in pregnancy rate and offspring rate between the transfer models, whereas significant differences were only found in survival rate when all transfers were analyzed (double: 24 +/- 4% vs single: 14 +/- 3%, P < 0.05). An effect of strain was detected in the pregnancy rate (NZ: 33% vs SB: 71%, P < 0.05; SY: 61%) and in the survival rate per donor doe on pregnant recipient doe (SY: 42 +/- 5 vs SB: 19 +/- 5, P < 0.05; NZ: 34 +/- 7%). These results suggest a differential embryo sensitivity with respect to their genetic origin in both the freezing-thawing and transfer procedures.

--[[User:Z3126328|Jin Lee]] 13:06, 3 September 2009 (EST)

[http://www.ncbi.nlm.nih.gov/pubmed/14064965?log$=activity]GROSS EFFECTS ON RABBIT EMBRYOS AND MEMBRANES OF X-IRRADIATION IN THE BLASTOCYST STAGE.

[http://www.ncbi.nlm.nih.gov/pubmed/11139224?ordinalpos=408&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum]Onset of zygotic transcription and maternal transcript legacy in the rabbit embryo.Brunet-Simon A, Henrion G, Renard JP, Duranthon V.
Laboratoire de Biologie du Développement, INRA, Jouy en Josas Cedex, France.

Onset of zygotic transcription is progressive from the one-cell stage onward in the rabbit embryo. Maternal transcripts remain fairly stable until the 8-16 cell stage when major transcriptional activation of the zygotic genome takes place. To understand the mechanisms of the maternal-to-zygotic transition in the genetic information governing development, we asked whether a progressive synthesis of zygotic transcripts takes over the maternal molecules, or whether the synthesis of zygotic transcripts is very abrupt and independent of the persistence of the maternal counterparts. To answer this question, we set up mRNA differential display experiments comparing the mRNA content of rabbit embryos at different stages during the preimplantation period. We isolated eight zygotic transcripts whose synthesis is abruptly turned on at the 8-16 cell stage. These transcripts are involved in general cellular metabolism and their maternal counterparts are still present up to the four-cell and even the 8-16 cell stage. This identification of early zygotic transcripts suggests that global long range modifications of chromatin structure result in a rapid increase in transcription rates during the major transcriptional activation of the zygotic genome.

[http://www.ncbi.nlm.nih.gov/pubmed/11245264?ordinalpos=409&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum]
Reconstruction of the heteroparental diploid condition in rabbit zygotes by nuclear transfer.Escribá MJ, García-Ximénez F.
Departamento de Ciencia Animal Universidad Politécnica de Valencia, Spain. mescriba@dca.upv.es

Studies on genomic imprinting showed that parental genomes have complementary roles during embryogenesis, are both essential and need to be synchronized in their embryonic stage for successful development to term. To our knowledge, these studies have not been performed in species other than mice. We studied the in vitro and in vivo development of reconstructed zygotes by combining female haploid nuclear donors and androgenetic hemizygous recipients. Haploid donor embryos at the 8- or 32-cell stage were obtained from electroactivated young rabbit ova (eight pulses maximum, consisting of 0 6 kVcm(-1) for 60 microsec each, 38 min apart) which were further cultured for 24 h or 32 h. Couplets formed by both the haploid male hemizygous recipients and haploid female donor cells were electrofused (2.2 kVcm(-1) for 60 microsec duration each, 30 min apart) and their nuclear configuration determined 122 of those fused (43%: 122/286) were diploid. Reconstructed diploid zygotes developed in vitro up to the compacted morula, blastocyst and hatched stages (1/8-nuclei x 50%, 18% and 9% vs. 1/32-nuclei: 47%, 25% and 19%; P > 0.05), respectively. In embryo transfer assays, both 1/32-reconstructed zygotes and control, non-manipulated zygotes were transferred to synchronized does Four live reconstructed fetuses (4/49: 8 1% survival rate) and five in regression stage (9/49: 18% implantation rate) were observed on Day 21 post-ovulation, whereas from control zygotes, 11 fetuses were alive (11/53 21% fetal survival rate) and 2 degenerated (13/53 x 24 5% implantation rate). Similar results were obtained from a final experiment, in which development was allowed to progress to term. Six live rabbit pups derived front experimentally reconstructed zygotes (11%; 6/54) and three fetuses in regression stage were obtained; values slightly lower than those derived from non-manipulated and transferred control zygotes (18% 9/50, live born rate).

[http://www.ncbi.nlm.nih.gov/pubmed/11589623?ordinalpos=412&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum]
Effects of leukaemia inhibitory factor on endometrial receptivity and its hormonal regulation in rabbits.Liu CQ, Yuan Y, Wang ZX.
Shanghai Institute of Planned Parenthood Research, Shanghai, P. R. China.

The effects of hormones on production of leukaemia inhibitory factor (LIF) and the uterine receptivity in rabbits were studied. In ovariectomised rabbits, LIF protein was not detected in control but upregulated by progesterone alone. Oestrogen had a slightly negative effect when the rabbits were treated with both oestrogen and progesterone. Mifepristone (Mi) inhibited the progesterone-stimulated production of LIF in rabbit uterus. The transfer of embryos to LIF-treated recipients significantly increased pregnancy rate (70%) and implantation rate (27%) as compared with control (pregnancy rate=40% and implantation rate=17%). The transfer of embryos to LIF and mifepristone-treated recipients significantly decreased pregnancy rate (30%) and implantation rate (9%). The results indicated that LIF protein had a beneficial effect on uterine receptivity and mifepristone prevented this effect. Copyright 2001 Academic Press.

[http://www.ncbi.nlm.nih.gov/pubmed/8447943]
Effects of strain and embryo transfer model (embryos from one versus two donor does/recipient) on results of cryopreservation in rabbit.Vicente JS, García-Ximénez F.
Departamento de Ciencia Animal, Universidad Politécnica de Valencia, Spain.

Differential effects of 2 transfer models for normal thawed embryos of 1 donor doe were studied on the offspring rate and their embryo survival at birth from 3 selected rabbit strains (SY and SB: synthetic strains, NZ: New Zealand White). Morulae were obtained 64-66 h post-coitum from 93 adult does treated with 25 IU of hCG (SY:36, NZ:27, SB:30). Morphologically normal morulae were frozen in the presence of 1.5M DMSO and stored in liquid nitrogen. Normal thawed embryos were transferred into the oviducts of synchronized recipient does of the same strain 48 h after being injected with 25 IU of hCG (SY:28, NZ:21, SB:24). Each recipient received embryos from 1 (single transfer) or 2 different donor does (double transfer). Significant differences were observed in the post-thawing percentage of normal embryos between strains (SY:95 +/- 1% and SB:85 +/- 3%, P < 0.05; NZ: ,91 +/- 2%). After transfer, no significant differences were observed in pregnancy rate and offspring rate between the transfer models, whereas significant differences were only found in survival rate when all transfers were analyzed (double: 24 +/- 4% vs single: 14 +/- 3%, P < 0.05). An effect of strain was detected in the pregnancy rate (NZ: 33% vs SB: 71%, P < 0.05; SY: 61%) and in the survival rate per donor doe on pregnant recipient doe (SY: 42 +/- 5 vs SB: 19 +/- 5, P < 0.05; NZ: 34 +/- 7%). These results suggest a differential embryo sensitivity with respect to their genetic origin in both the freezing-thawing and transfer procedures.

[http://www.ncbi.nlm.nih.gov/pubmed/14564113]
'''Developmental stages in the rabbit embryo: guidelines to choose an appropriate experimental model.'''Beaudoin S, Barbet P, Bargy F.
Department of Pediatric Surgery, Groupe Hospitalier Cochin-Saint-Vincent de Paul, Paris, France. sylvie.beaudoine@svp.ap-hop-paris.fr

Researchers involved in the field of congenital malformations are often forced to work on an animal model. Both accurate description of its normal development and comparative staging with human development will be mandatory. To complete the lacking medical literature, we herein provide such data for the rabbit model. Sampled rabbit embryos were staged using the Carnegie criteria, in order first to determine if they were consistent with the rabbit developmental pattern, and second to compare this pattern with the human one. Our results show a suitable comparison of rabbits and humans in early developmental stages, except for the neural growth. Copyright 2003 S. Karger AG, Basel

Talk:2009 Group Project 1

2009-10-14T09:06:33Z

Z3185685: /* Actual Changes Made */

== Lab 10 ==
--[[User:Z3283499|Antonio Lee]] 10:52, 2 October 2009 (EST) Hi everyone, I will be working with you during the Lab10 Tutorial and here is the news link and PDF of the manuscript for your group exercise. I encourage you to read the paper before the tutorial. Also, please indicate next to the questions below (using either your initials or student number) which one of the four questions you wish to address.
:'''Group 1 :''' [http://www.nature.com/nature/journal/v461/n7262/full/461354a.html '''Developmental biology: Asexual healing'''] in Nature News and Views - Nature 461, 354-355 (17 September 2009) [[Media:ANAT2341_Lab10_2009_Group 1 Reading.pdf|Manuscript (PDF): Mitochondrial gene replacement in primate offspring and embryonic stem cells]]

:Question 1. What is the background to the existing problem / disease condition? --[[User:Z3187802|Vishnnu Shanmugam]] 22:12, 2 October 2009 (EST)

Mitochondria are found in all eukaryotic cells and contain their own genome (mitochondrial DNA or mtDNA). Unlike the nuclear genome, which is derived from both the egg and sperm at fertilization, the mtDNA in the embryo is derived almost exclusively from the egg; it is of maternal origin.

Mutations in mitochondrial DNA (mtDNA) can lead to a range of chronic incurable diseases such as myopathies, neurodegenerative diseases, diabetes, cancer and infertility. Mutations in mitochondrial DNA could also contribute to other diseases such as Alzheimer’s,
Parkinson’s and Huntington’s diseases

A normal cell should be homoplasmic in its mitochondrial DNA, that is it should only contain one type of mitochondrial DNA. But if the cell has two or more types of mitochondrial DNA (a mixture of normal and mutated DNA) it is known as heteroplasmic and can lead to a range of diseases. These genetic mutations can also be passed to offspring causing disease.
1 in 3,500–6,000 are at risk or presently have a disorder from mutations in mitochondrial DNA. Disease progresses slowly and there are no cure. Limitations in assessing the extent heteroplasmy and accuracy in calculating the risks of developing mtDNA related disease means that a new approach is needed to tackle the problem.

:Question 2. What approach / method did the research team take to tackle / improve the problem?--[[User:Z3126328|Jin Lee]] 12:31, 7 October 2009 (EST)
:Working with rhesus macaque monkeys, the authors reconstructed mature oocytes containing the nuclear genome from one oocyte and the mitochondrial genome from another. To do this they removed the nuclear genetic material from one oocyte, leaving behind all of the mitochondrial DNA, then transferred it to another oocyte whose nucleus had been removed (a cytoplast), but which contained a full complement of mitochondrial DNA.

:Question 3. What was the breakthrough / major advancement OR failure / drawback? and why might this be of significance?
::Drawbacks - --[[User:Z3186093|Jenny Guy]] 22:43, 7 October 2009 (EST)
:::There were difficulties in visualising and isolating the intact chromosomes, as well as the mtDNA being susceptible to damage and translocation/movement. Visualization became easier after the development of techniques for DNA staining with fluorophores and looking under UV light during embryo cloning by the SCNT (somatic cell nuclear transfer). Successful implementation to avoid damage to the cytoplast during spindle removal involved using polarized microscopy. (p368) --[[User:Z3186093|Jenny Guy]] 14:12, 8 October 2009 (EST)
:Question 4. What are the next steps in moving forward? What are the next or new hurdles to overcome?

==Actual Changes Made==

'''Concise Version:''' (Everyone add their changes here)
# Removed cleft palate and cleft lip section (Abnormal development) --[[User:Z3187802|Vishnnu Shanmugam]]
# Altered references (current research and abnormal development) --[[User:Z3187802|Vishnnu Shanmugam]]
# Added picture guide for transgenic rabbit --[[User:Z3187802|Vishnnu Shanmugam]]
# Added picture guide for rabbit cloning --[[User:Z3187802|Vishnnu Shanmugam]]
# Removed newspaper image of rabbit (Current research) --[[User:Z3187802|Vishnnu Shanmugam]]
# Formatted pictures and text to reduce gaps in the assignment (current research and abnormal development) --[[User:Z3187802|Vishnnu Shanmugam]]
# Corrected spelling mistakes in images (current research and abnormal development) --[[User:Z3187802|Vishnnu Shanmugam]]
# Reviewed all images and have written a summary, original source, copyright information (current research and abnormal development) --[[User:Z3187802|Vishnnu Shanmugam]]
# Formatted the look of the genetics section, including 'abnormalities' --[[User:Z3186093|Jenny Guy]] 16:31, 14 October 2009 (EST)
# Fiddled with position of images in genetics section --[[User:Z3186093|Jenny Guy]] 16:31, 14 October 2009 (EST)
# Fixed spelling mistake in History - Jin Lee
# Sum have you changed anything? Haven't heard from you in a while! - Jenny
Yep jenny doing it now - Sum

'''Long Version:'''

--[[User:Z3187802|Vishnnu Shanmugam]] 23:46, 10 October 2009 (EST) Okies, all done. I'm going to review all my images and add summaries to them. Dr. Hill asked for a concise version to all the changes we make from the peer review process. I suggest everyone add their changes to the list I have started above and place your signature next to it.

--[[User:Z3186093|Jenny Guy]] 14:29, 10 October 2009 (EST)Hey vishnuu, i was thinking could you please alter
* the gaps between the spina bifida images (format this somehow with the images on the side and text on the other)
* the gap under "Brachydactylia & Acheiropodia"...maybe you have entered down too much????
cheers :)

--[[User:Z3187802|Vishnnu Shanmugam]] 21:27, 9 October 2009 (EST)Hey all. I have removed the newspaper image of rabbit (Due to copyright issues), and have replaced it with a series of images that guides the reader through the process of cloning a rabbit. I have NOT altered the text summarizing the creation of transgenic and clone rabbits as there are very important & detailed information which if removed puts complex processes in danger of oversimplification. I also corrected spelling mistakes in some images.

--[[User:Z3187802|Vishnnu Shanmugam]] 20:22, 7 October 2009 (EST) Hey gang. By popular demand (or the stress of reading) people want less text. I have removed the entire cleft palate & cleft lip section from abnormal development. For current research, I have also created a step by step picture guide for transgenic rabbit creation. It was initially meant to be a video, but this wiki page does not display (.gif) or (.mov) files. Sum, I remember that you did your references after me...so when I removed the cleft palate & cleft lip section, the references changed....so I have also adjusted your references accordingly. I don't think it is necessary to make all the changes outlined below as most comments are subjective (different people have different preferences) and seems like some comments were made because people had nothing else to propose.

--[[User:Z3126328|Jin Lee]] 10:01, 8 October 2009 (EST)Hi Guys, I have fixed spelling mistake and some people commented to make table form for advantages and disvantages section. But I liked the way I presented so I will leave in point form.

--[[User:Z3186093|Jenny Guy]] 14:32, 8 October 2009 (EST)
Hey! I looked at what i could change in the genetics section and decided to format a little. Our peers asked:
* genome information into a table - this is a little silly since there'd only be one column.
* Reformating in sections such as hitory and genetics. - have tried to do a little.
* Make pictures appear on the same side of page. maybe aligning the pics on either the left or right side instead of both left and right, and possibly putting them as thumbnails could also work. - i tried to put both of the chromosome images ont he same side (tried both left and right) but found that it looked terrible considering the size (which is needed to see it) as the text wouldnt fit around it very well.
* it will look much better if there is some work to be done for the structure of it especially the paragraph under the heading of 'abnormalities'. - am still in the process. not sure what else i can do since its in basic dot point form with not a large text to format. any ideas? or shall i leave it how it is now?
* maybe instead of writing the entire reference, you could just state The Broad Institute or just the people related to it - i feel that the entire team needs a mention since all people relate to it. noting just the broad institute is almost like noting a team of people here in unsw as just plainly "UNSW" which is just disrespectful.

==Things to work on noted by peers==

Hey, So the changes i will make will be in the introduction section. Also a lot of people have said to add pictures in the stages section to make it more interesting. I couldnt get permission to use the images so i bought tracing paper today! lol will try to draw them and see if they are ok enough to add. I think i am going to leave the timeline section as is because most people liked it. What do u guys think? --[[User:Z3185685|Sumaiya Rahman]] 15:31, 8 October 2009 (EST)

Sounds great Sum....Its gonna take some effort to trace it then scan it. GL --[[User:Z3187802|Vishnnu Shanmugam]] 21:37, 9 October 2009 (EST)

Hey guys,
I read through all the notes our peers have given us and summarised them into the following sections. Majority of them overlap (where ive put a new persons opinions in the same dot point over and over to stress the point on how many people noticed). Some things are easily changed, most of all i reckon its
# formatting
# pictures
# text to be more concise
So we just need to finalise all these minor things to improve our project. Please detail any changes you've made in the the heading above.
Cheers, --[[User:Z3186093|Jenny Guy]] 20:30, 7 October 2009 (EST)

INTRODUCTION
* a little too brief, more information needed
* For the first sentence (the characteristics that make the rabbit an excellent model for study), mention the section 'Why are we using rabbits?' under History section.
* For the second sentence (study that developed and improved micromanipulation techniques), mention the 'Transgenic Rabbit' section below under the genetics section. I've read the entire project page, and the introduction was the only place I found that was not precise enough (which is a great thing). These are minor things, but I think they will help with improving your project page.
*suggestion: Place the history section after the Introduction. This gives the viewer an overview of the use of the rabbit embryo. This way the viewer is first subjected to a few examples of the rabbit embryos use. It also allows him/her to understand where the rabbit embryo sits in with history. I guess this is a matter of personal preference.

HISTORY
* The advantages and Disadvantages would be better in a table. the history you might want to put the advantages and disadvantages into a table to make the page look a bit more tidy and easier to read when we go through it.
* The usage of rabbits for experimental models in science and medicine could be stated under the history section to allow background information for the readers to become aware of the topic and why the rabbit have been used to study specfic medical procedures and diseases.
* Spelling mistake under 'Discovery of Graafian Follicle', 2nd paragraph. I think it's previous instead of 'previcous'.
* Reformating in sections such as hitory and genetics. Make pictures appear on the same side of page.
* The history section can be improved if the infomation is expanded to give some more detailed background knowledge although i like the idea that the information is concise describing each scientists contribution towards the model.
* could be formatted to make the information stand out and a lot more appealing, I would recommend including pictures if possible that link to the text and making the advantages and disadvantages into a table rather than listing it.

TIMELINE
* more images to wholly understand. timeline/staging section was clear and concise, however it could be improved by adding more colour/pictures to maintain the readers' interest. The timeline and staging bits are very well written and clear but i think you should add a few images in there to match up with the text. Perhaps some pictures of embryos throughout development. Pictures for every stage would make it more visually attractive rather than just reading text. lack of pics in the timeline.
* It’s a little confusing that the development jumps back and forth according to the body part developing. Maybe it should be categorised according to time of development instead for greater clarity at first glance
* The timeline is just a little confusing, as its divided into development of different parts, which breaks the time flow.
* some of the information for the timeline section was too heavy for the page - would recommend only using some of the information on your actual page and having the rest as links to separate pages

STAGING
* pictures for stages would have been nice, unless there were none????
* a more even distribution of information, particularly more detail in the stages
* Provide pictures for individual stages. Get visual, and make the stages interesting to read. include pictures in the stages section.
* Staging section is also very well presented but the information presented in a table would even look better if there is use of some pictures to make it more interesting for its audience.
* staging section was very bland and would be more appealing with pictures. I dont think its necessary to cite your entire reference within the text

GENETICS
* genome information into a table
* Reformating in sections such as hitory and genetics.
* Make pictures appear on the same side of page. maybe aligning the pics on either the left or right side instead of both left and right, and possibly putting them as thumbnails could also work.
* it will look much better if there is some work to be done for the structure of it especially the paragraph under the heading of 'abnormalities'.
* maybe instead of writing the entire reference, you could just state The Broad Institute or just the people related to it

ABNORMAL DEVELOPMENT
* There is also a lot of content which might be alleviated by reducing the section on abnormal development. Too much information about the abnormalities. make more concise.
* the abnormalities went a bit over board, and didn't need that much attention I think (as compared witht the research which was good)
* reduce the writing content. for example. In the current research section, you have two scientific process of transgenic rabbits as well as cloning which is described in how these are done. why not draw a step by step diagram, and put these written steps in the link to the image.
* The information provided under Hydrocephalus and Brachydactylia was informative and interesting, but it contained too much text. I suggest you narrow it down and make use of Dots point, numbering, bold/italic words, and/or sub-sub-headings.
* Section for "Abnormal Development" gives the readers useful amount of information but i think its very lenghty, use of dot points can make it look even better and easy to understand.

CURRENT RESEARCH
* the group makes good usage of diagrams but towards the end diagrams die out, you might want to make the current research part of your assignment into diagrams and steps as there is just a bunch of information thrown there and alot of reading needed, if you put it into steps or diagrams it will make the marking process and reading process easier and allow us as reader to understand the information with ease.
* 'Transgenic Rabbit' should be shifted toward the genetic information on the rabbit. (Jenny - i dont agree with this as its research, not its offical genetics. Vishnnu - Neither do I)
* information in regard to stem cells should be brief and truncated. Example in regard to stem cell research should have brief and simple model explaining the process and why it used.
* There is too much information under stem cells. There is 2 examples of studies dealing with stem cells. A suggestion would be to just have one, and have a link saying 'Koga's research on Stem Cells'.
* Have the section 'links to Research labs and researchers' placed at the end of current research. That way, the information on the page will flow smoother.
* more of a focus on current research i.e. what each method is being used for and less on the process behind each method.
* great amount of information but in my perspective replacing the paragraphs with some dot points with heading and subheadings would further enrich understanding of readers.

OVERALL
* "As you start going down the page though the information starts to read a bit haphazardly, for example the developing body; jumping for section to section and the timeline section. it would be great if you could clean this up as it doesn't really flow." - formatting
* condense long slabs of text as the page is long
* format it so there are no huge gaps
* move the links to current research labs up closer to the current research section, just to keep it all together

==Constructive Criticism of Coordinator==
--[[User:S8600021|Mark Hill]] 08:07, 8 October 2009 (EST) The following comments are general in nature in no specific order, as it would be inappropriate to suggest specific changes and then assess the final project. Comments will be added during this week and you still have one week before final submission.

* There is no concise list of changes made to your project on the basis of peer assessments.
* Timeline of Embryo Development early stages, are in the introductory text said to be in hours, but it would be good to see it in the list as well.
* [[:File:Sizes.JPG]] Relative sizes, but no absolute size or scale given.
* A general comment about images. When you click an image and it opens, the information below the image should have an explanation of what the image shows, a reference (if from a paper) and a link to the original source (if available) as well as copyright information.
* Did you actually read the terms of use for this image that you cut n pated into the image description? [[:File:Rabbit_hybrid.jpg]] "For this purpose alone you may retrieve and display the Content on a computer screen. You may also print out, but not photocopy, one copy of individual files on paper and store files in electronic form on disc, but not on any server or any other storage device connected to a network where the Content could be accessed by other users." It clearly states that you cannot use this image online.
* Chromosomes section, images have no legends and structure not clearly organised.
* There needs to be better checking of your spelling and grammar, for example [[:File:Rabbitmalformation3.jpg]] "Plant Patkology of Tke Rockefeller Institute for Medical Researck", these mistakes while not major, suggests a lack of reviewing of your work by the group.
* Just a comment on project "feel", when several people work together on a project and insert their parts, the final project sometimes has an uneven style. Now that you have time to tidy up, try and get a common appearance throughout your project.

==Constructive Criticism of Peers==

--[[User:Z3218657|Sally Clarke]] 09:32, 1 October 2009 (EST)
Nice work Guys!
- Fantastic images used throughout - maybe a few more in the timeline so we can understand what is going on
- As you start going down the page though the information starts to read a bit haphazardly, for example the developing body; jumping for section to section and the timeline section. it would be great if you could clean this up as it doesn't really flow.
- The section on the abnormal development is great.
- The page is quite long - Maybe you could condense some of the text as it is kind of slab like
- i really enjoyed the breeding section
- The advantages and Disadvantages would be better in a table.

--[[User:Z3223194|Bronwyn Lewis-Jones]] 08:08, 1 October 2009 (EST) Hi Group 1! This is obviously a well organised and well researched assignment. I found it very informative. There are (of course) some things I feel could improve the overall submission. I loved that the timeline/staging section was clear and concise, however I think it could be improved by adding more colour/pictures to maintain the readers' interest. There is also a lot of content which might be alleviated by reducing the section on abnormal development. Hope this helps :)

--[[User:Z3218146|Julianna Lam]] 01:11, 1 October 2009 (EST) good job guys.
-Theres alot of relevant information.
-The timeline and staging bits are very well written and clear but i think you should add a few images in there to match up with the text.
-The image for the genetics bit is awesome.
-The page is nicely set out.
-Too much information about the abnormalities.

--[[User:Z3258567|Sando Rashed]] 20:04, 30 September 2009 (EST)hey guys, your page looks good, starts off well as there is not a bunch of information just thrown in, the information used is well thought, with the history you might want to put the advantages and disadvantages into a table to make the page look a bit more tidy and easier to read when we go through it (you can also do this with the info under genome), the group makes good usage of diagrams but towards the end diagrams die out, you might want to make the current research part of your assignment into diagrams and steps as there is just a bunch of information thrown there and alot of reading needed, if you put it into steps or diagrams it will make the marking process and reading process easier and allow us as reader to understand the information with ease, other than that the page looks quite good, well done on all your contributions

--[[User:Z3218792|Gabriela Pinget]] 21:51, 29 September 2009 (EST)

Nice page. I particularly liked the idea of lists of what is to come before each flood of information as was done with the ‘history of model use’ section.

- Nice easing into the topic with ‘advantages’ and ‘disadvantages’ lists.

- I liked the of rabbit embryo development to that of humans- puts it into perspective

- Good glossary- informative but not over- the- top

- Nice genetics section! Easy to read and a great use of illustrations to break up the information

- I also like that you took a page out of Mark’s book in the addition of the abnormalities section

Improvements:

- Perhaps some pictures of embryos throughout development.

- It’s a little confusing that the development jumps back and forth according to the body part developing. Maybe it should be categorised according to time of development instead for greater clarity at first glance

--[[User:Z3295026|Joe Nassif]] 17:01, 29 September 2009 (EST)

Your assessment has come along great in regard to the criteria format. There are a few alterations that could improve your project, the following alterations may enhance your wiki page:

'''-''' The usage of rabbits for experimental models in both science and medicine could be state under the history section to allow background information for the readers to become aware of the topic and why the rabbit have been used to study specfic medical procedures and diseases.

'''-''' Secondly the information on 'Transgenic Rabbit' should be shifted toward the genetic information on the rabbit. So far the project is looking and coming along great except for minor edits.

'''-''' Background information should be placed subsequent to the introduction allowing the reader to understand why this specific animal is used for specfic purposes.

'''-''' Figures/Graphs and the illustration of the anatomy and genetic development of the embryo were useful and clear allowing the viwers to understand and learn through the demonstration of pictures which were extremely informative.

'''-''' Genetics: the Genetics and Abnormalities information was great and very informative. It was great how the group compared the embryo with the human chromosome allowing the audience to understand the difference between both.

'''-''' Abnormalities: Information and details which were in the genetic section provided informative and interesting information, and it could be truncated a bit, additionally just discussing the chromosome development of the rabbit.

'''-''' Current Embryology Research: information in regard to stem cells should be brief and truncated. Example in regard to stem cell research should have brief and simple model explaining the process and why it used.

'''-''' Consequently, I thought the project was good it flowed and was very informative. The information was detailed, and the illustrations were useful and allowed the readers to gain a brief overview on the topic and it usage in history and in current research. Overall group 1 seem to achieve the critriea outcomes and summarised the topic really well, the comparsion to human embryo development througout the text was great and is a good referencing point in comparsion to the species choosen.
Great job --[[User:Z3295026|Joe Nassif]] 17:01, 29 September 2009 (EST)

--[[User:Z3255007|Sadaf Masood]] 12:09, 30 September 2009 (EST)Hello Group 1! Congrats on your awesome group project! I must say im very impressed with all the information you have posted and i have listed down the good bits and the bits that need to be improved. Since i am posting this a lil late, i have seen that u have already improved your project and few aspects...Good Job guys!

1. Very brief introduction...maybe just a little bit more info will be perfect

2. Abnormalities section is very informative and well researched, but very long, how about making it a little more precise?

3. The Advantages and Disadvantages of the using Rabbit is just simply perfect

4. The timeline is just a little confusing, as its divided into development of different parts, which breaks the time flow.

5. Pictures for every stage would make it more visually attractive rather than just reading text

6. Great Glossary!

There were few things earlier that need to be improved but you guys fixed it as soon as comments were posted so basically you guys rock :)An excellent effort guys. Best Wishes

# --[[User:Z3217015|Mitchell Mathieson]] 09:45, 25 September 2009 (EST)Very nice. The information was maybe a bit spread out, with heaps of gaps everywhere (formatting???), but the information was there, and relevant, and easy to read. I like how there was tonnes of information on current research, as I think that was the main aim, but the abnormalities went a bit over board, and didn't need that much attention I think. pictures for stages would have been nice, unless there were none???? The references are top notch, and the glossary is pretty amazing, and in the right place. Overall very good, I think formatting was the major downfall though, as it makes the page that much longer, and hence a little bit more difficult to read.

--[[User:Z3224449|Elide Newton]] 14:12, 26 September 2009 (EST)
HEllO GROUP 1: Well done on such a great assignemnt, looks like you have all worked very hard. Well my one point of constructive criticism would be to reduce the writing content. for example. In the current research section, you have two scientific process of transgenic rabbits as well as cloning which is described in how these are done. why not draw a step by step diagram, and put these written steps in the link to the image. that way it is more visual, the info is still there under the image link, and the page wont look as daunting to read. :) hope this helps!

--[[User:Z3254857|Begum Sonmez]] 00:46, 26 September 2009 (EST)
Hello Group 1. Firstly, I would like to let you all know that you have all done a great job. I'm impressed. I have a few suggestions that I think mite help to improve the page even more:

*Introduction:

1)For the first sentence (the characteristics that make the rabbit an excellent model for study), mention the section 'Why are we using rabbits?' under History section.

2)For the second sentence (study that developed and improved micromanipulation techniques), mention the 'Transgenic Rabbit' section below under the genetics section. I've read the entire project page, and the introduction was the only place I found that was not precise enough (which is a great thing). These are minor things, but I think they will help with improving your project page.

3)Breeding information was informative.

4) A suggestion: Place the history section after the Introduction. This gives the viewer an overview of the use of the rabbit embryo. This way the viewer is first subjected to a few examples of the rabbit embryos use. It also allows him/her to understand where the rabbit embryo sits in with history. I guess this is a matter of personal preference.

*Timeline:

1)Graphs, and the illustration of the zona pellucida and mucin coat were very clear and informative.

*Staging: I had no problems with it. The lack of information I think was a plus. It touched on the content in the Timeline section.

*History:

1) I loved the idea of the 'Disadvantages' of the rabbit embryo, it seemed unbiased. The brief timeline provided a clear and short summary.

2) Spelling mistake under 'Discovery of Graafian Follicle', 2nd paragraph. I think it's previous instead of 'previcous'. Also, the 2nd paragraph under this heading does not flow that well. Try rephrasing the 2nd sentence.

*Genetics:

The Genetics and Abnormalities section flow into eachother very well. I appreciated the comparison of the rabbit chromosome to the human chromosome.

*Abnormalities:

1) The information provided under Hydrocephalus and Brachydactylia was informative and interesting, but it contained too much text. I suggest you narrow it down and make use of Dots point, numbering, bold/italic words, and/or sub-sub-headings.

*Current Embryology Research:
1) There is too much information under stem cells. There is 2 examples of studies dealing with stem cells. A suggestion would be to just have one, and have a link saying 'Koga's research on Stem Cells'.

2) Have the section 'links to Research labs and researchers' placed at the end of current research. That way, the information on the page will flow smoother.

Overall, I thought there was a consistent structure in each section. The information was informative, and the pictures were relevant and helped me better understand the topics of discussion.

--[[User:Z3252340|Emily Wong]] 10:58, 27 September 2009 (EST) Firstly, great work. It is a well researched, structured and organised page. The content is very in depth and includes information on all of the specified areas. It is well referenced, with an extensive reference list indicating the amount of research put into the page. Some areas are more detailed than others. For example, the staging section is quite short and concise where as the Abnormal development section is extremely long considering it is not a needed topic. There is moderate use of pictures and diagrams, but more use could benefit the page as it may be able to negate some of the large slabs of text. The comparisons made between the human and the rabbit embryos are a good part of the project page. Each member of the group has contributed to the page and provided a lot of information on the section of content they were working on. What would improve this project is a more even distribution of information, particularly more detail in the stages, a few more diagrams or pictures to negate some of the text presented, more of a focus on current research i.e. what each method is being used for and less on the process behind each method.

--[[User:Z3126345|Gang Liu]] 14:26, 27 September 2009 (EST)In my opionion, this is a well constructed page. It includes major subheadings such as history, timeline, stages, genetics and current research. It is very concise and straightforward, which makes it easy to read. For example, a short introduction paragraph,"...the rabbit is an appropriate animal model as the results from many experiments are significant to that of other mammals, including humans.", explains to reader why rabbit is such a suitable model.

It also provides a logic flow. For example, in history of rabbit model use section, it has provided advangtages and disadvantages of model use. This is appropriate, as it demonstrates the significance of rabbit model use in scitific discovery. In addition, it has provided detailed background information for each discovery. This makes it interesting to read.

It is also important to compare development of embryo between rabbit and human. For example, "... the similarities of this developmental pattern in humans and rabbits, suggests that the same growth increment is required to achieve the same stage. The main difference observed between human rabbit gestational duration is due to the fetal growth phase...", this has suggested human and rabbit share many similarities. Not only this page has demonstrated detailed written information of timeline development, it also provided graphics to reinforce the concept. For example, the hand drawing of developing embryo. As well as the comparison between human embryo and rabbit embryo timeline development.

It is also interesting to learn that rabbits have 22 pairs of chromosome, whereas humans have 23 pairs of chromosome.

Sections such as abnormal development and current research have demonstrated extended research and understanding. For example, hydrocephalus, spina Bifida, stem cell research and cloning techniques. All of these have showed the in depth research in textbooks, journals and internet based literatures.

However, this page can be improved by considering the following points.

*Provide pictures for individual stages. Get visual, and make the stages interesting to read.

*Reformating in sections such as hitory and genetics. Make pictures appear on the same side of page.

*Typo: "A rabbits potential for reproduction..."

*Sections such as abnormal development and current research are too lengthy. Might consider shrink the content.

*Lack of glossary.

Overall, big thumbs up!

--[[User:Z3252231|Angama Yaquobi]] 01:12, 28 September 2009 (EST)
First of all i would like to congratulate all the team members for a great team work.
Well done guys!! The group project looks amazing, the information presented is very concise
and straight to the point which makes it very easy for the readers to grab
the important information that they need to enhance their knowledge.
I like the section of history, the information is very clear,
and i like the idea of providing some background knowledge to the readers
about the disadvantages of the use of rabbit.
The history section can be improved if the infomation is expanded
to give some more detailed background knowledge althought
i like the idea that the information is concise describing each
scientists contribution towards the model.
The section for timeline is impressive, in my perspective its a great idea to cover alot of content in a very smart way
which is by the use of subheadings to make it easy to understand for audience.
Staging section is also very well presented but the information presented
in a table would even look better if there is use of some pictures
to make it more interesting for its audience. Genetics section
is beautifully presented, all the information is there with some
amazing pictures but will look much better if there is some work to
be done for the structure of it especially the paragraph under the
heading of 'abnormalities'. Section for "Abnormal Development" gives
the readers useful amount of information but i think its very lenghty,
use of dot points can make it look even better and easy to understand.
The same for Current embryology research, great amount of information but
in my perspective replacing the paragraphs with some dot points with
heading and subheadings would further enrich understanding of readers.
Also glossary would complement the webpage. But overall,
great amount of information which shows alot of research
which has been done by all the team members. Well done guys!!

--[[User:Z3217686|Thomas Dangerfield]] 13:29, 28 September 2009 (EST) Hey guys! Good work on your assignment! Plenty of info which is good, and very well referenced. The glossary is a good idea too! I do agree with a few others about the lots of clear spaces in the formatting, and the lack of pics in the timeline though. Also under the genetics section, maybe aligning the pics on either the left or right side instead of both left and right, and possibly putting them as thumbnails could also work. In the abnormalities section, there might have been a little too much info that probably wasn't needed, but i do like the effort put in. Over all, possibly more time spent on formatting and determining which sections are more important and which sections may need to be limited. Other than those points, the whole assignment seemed very well done!

--[[User:Z3215682|Carly Mooney]] 11:32, 29 September 2009 (EST)
You assignment is visually appealing and the genetic information e.g. the number of chromosomes of a rabbit was very interesting.There are some additional sections you have added which really complement your assignment e.g the abnormalities and I really liked the advantages and disadvantages of using the rabbit model. The few suggestions I would make is to:
* include pictures in the stages section
*place the pictures throughout the text (e.g. to left or right). You did this up until abnormalities and I felt it broke the flow of the written text.
* and maybe move the links to current research labs up closer to the current research section, just to keep it all together.
Overall very impressive though.

--[[User:Z3220040|Joanne Raffel]] 15:25, 29 September 2009 (EST) Nice wikipage, the page looked interesting however I agree with some others that the formatting of the page was inconsistent. I thought the referencing was great but found it a bit confusing with the reference numbers after the paragraphs. I thought the subheadings werent distinct enough, especially in relation to the text, which made it difficult to read. The history section could be formatted to make the information stand out and a lot more appealing, I would recommend including pictures if possible that link to the text and making the advantages and disadvantages into a table rather than listing it. I especially liked the comparison between the rabbit and the human embryo, however some of the information for the timeline section was too heavy for the page, I would recommend only using some of the information on your actual page and having the rest as links to separate pages. The staging section was very bland and would be more appealing with pictures. I dont think its necessary to cite your entire reference within the text, especially in the genetics section, maybe instead of writing the entire reference, you could just state The Broad Institute or just the people related to it. The abnormalities section was a good inclusion however it was very extensive, along with the current research section. Overall a very good wikipage.

----
*Hey, Well done guys!!! I think our group worked pretty well! I think we communicated each other well and did very best for their section. I fixed my spelling mistake and problem with sentence! As Begum mentioned, I think placing the history part after the introduction is better idea. --[[User:Z3126328|Jin Lee]] 13:36, 26 September 2009 (EST)

*Hey guys,
the project has come together brilliantly! it looks quite good. Hopefully mark will like it! ill add some terms to the glossary and try do some formatting (the first image is a little too big i think!) --[[User:Z3186093|Jenny Guy]] 10:28, 24 September 2009 (EST)

Hey. Yep all good. I had to get rid of the pics, so stages table is now blank. Im pretty much done. I'll see what i can add to the glossary. thanks :)--[[User:Z3185685|Sumaiya Rahman]] 23:34, 23 September 2009 (EST)

Hey all, I'm going to start a glossary and add it under the reference section. Scan your text and add to the glossary in alphabetical order. Also under the marking criteria, it says to provide links to researchers and research laboratories.....i'll start that under the glossary. Everyone else OK with their stuff?--[[User:Z3187802|Vishnnu Shanmugam]] 23:08, 23 September 2009 (EST)

Hey Sum, The images look fine but I don't think you can use the images like that since the journal KARGER is being particular about its copyright laws. I tried tracing around the images but it does not seem to resemble anything like an embryo. I did however find this link...go to it and scroll down to the images of the developing embryo. You might be able to edit it to resemble rabbit embryo. --[[User:Z3187802|Vishnnu Shanmugam]] 15:10, 23 September 2009 (EST). To get to the link, Google image search "rabbit gestation"....click on the "rabbit,gestation age" image from nature.com
Also google image search "The Haeckel embryo sequence"...could be useful after some editing

oh my god!! I summarised all of my research and wrote down on the page. Then I blew up everything!!!
it says 'edit conflict' what da?? I lost all of my work...it was my stupid mistake...--[[User:Z3126328|Jin Lee]] 01:06, 23 September 2009 (EST)

Oh also.. let me know if the images look stupid --[[User:Z3185685|Sumaiya Rahman]] 00:34, 23 September 2009 (EST)

Hey thanks vishnuu. I put some images up in the stages table. I did edit the pictures, but im not sure if im allowed to use it like this? have a look and let me know. Also im not sure what is going on with the reference section seems kinda all over the place, so i havnt added mine in yet. Maybe we should fix that up somehow? :) oh LOL about the breeding rabbits bit! haha
--[[User:Z3185685|Sumaiya Rahman]] 00:31, 23 September 2009 (EST)

Hey Sum, Sorry for the late reply. For $330, I'd rather breed rabbits and take the photos myself. I had a look at the original images, what we can do is trace around the developing rabbit embryo using the pencil tool on an image editing software(eg. microsoft paint - already preloaded into most windows). Then upload the image to the assignment. Does your PC have adobe fireworks?...extremely good for tracing images. If not, have a go at it with microsoft paint....I shall also have a go at it, then I shall let you know on this discussion page at about 3PM t'morrow. If any good then I'll send it to your student email. If not, we discuss potential alternatives. good luck Sum! --[[User:Z3187802|Vishnnu Shanmugam]] 23:51, 22 September 2009 (EST)

Yep thats the article i used for the developmental stages and put in a table. I should have my timeline posted by end of today. I also couldn't get permission to use the pictures as they wanted about $330 for me to use it!! no thanks. I'll see if i can work it in somehow. Vishnuu did u have any ideas on editing the images?? --[[User:Z3185685|Sumaiya Rahman]] 12:29, 22 September 2009 (EST)

Have a look at this article, it's helpful for comparison bt rabbit and human in developmental stages!--[[User:Z3126328|Jin Lee]] 13:35, 21 September 2009 (EST)
*Sampled rabbit embryos were staged using the Carnegie criteria, in order first to determine if they were consistent with the rabbit developmental pattern, and second to compare this pattern with the human one. Our results show a suitable '''comparison of rabbits and humans in early developmental stages''', except for the neural growth.
[http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowAbstract&ArtikelNr=73136&Ausgabe=229537&ProduktNr=224239
]

Absolutely correct Juliana, my research articles and their links are labelled 1-6 so far, the rest is yours..... I'll fix it for you. A timeline image seems tricky and i'm unsure, send Dr. Hill an email on m.hill@unsw.edu.au and see what he says. We still have till thursday to finish everything, so don't be too worried....try to finish all your other stuff and leave the drawing of the timeline last.--[[User:Z3187802|Vishnnu Shanmugam]] 17:49, 20 September 2009 (EST)

*no.1-7 in reference section is mine. and I think links under Vishnnu's research on the discussion board is mine. let me know please. (I can't remember all of my researches)
I want to make a timeline image but I can't do it;;; I asked Mark few weeks ago but havn't replied yet....can somebody help me???--[[User:Z3126328|Jin Lee]] 17:26, 20 September 2009 (EST)

'''** Hey Jenny, dont worry!! the project is not due until next week! (24th) we will have it done by then!! I am still waiting for permission to use the pictures in my stages section, thats why it hasnt been done yet. Hopefully i can get permission, otherwise i'll have to draw them (or something) myself.''' --[[User:Z3185685|Sumaiya Rahman]] 14:03, 17 September 2009 (EST)

It says project due date 24th september.......if the due date had been brought forward why was it not posted on the project main page? --[[User:Z3187802|Vishnnu Shanmugam]] 13:48, 17 September 2009 (EST)

EVERYONE...WHY IS THE REST OF OUR PROJECT NOT DONE??
* vishnuu...its due TODAY!! how can you post things up next Monday? Please make sure youve referenced EVERY image and all text (i know youve said you need to do this...but its easiest done when writing the section as now you have to go back and find everything, insert numbers etc. Remember to put the reference in the reference section. For the current research section i thought this might help you (as during my lecture in another class they spoke about how rabbits are used in heart development. Is there anything that you've found to include this?). Also I found this website during my research so it may help you? [http://www.evergen.com/rabbit_experience.html/ Rabbit Experiments]
* sum - where is the timeline???? It doesn't exist? Where is it? Also, we need some sort of visual for the staging. Have you found an images? Could you draw the stages of embryo development? It just looks incredibly boring.
* julianna...you need to put up more other than just two historians...there is NO referencing whatsoever in your entire section. where have you found this information? have you put it in your own words or copied it? You need to add some more refences to the reference section at the bottom..there just aren't many to back up your research.

seriously guys. ive added photos and tried to spice up the project but i am NOT going to finish your sections for you. ITS DUE IN 3 HRS! i cant believe you guys haven't bothered to even try finish this. Im very disappointed and i think its slack to let the team down. --[[User:Z3186093|Jenny Guy]] 10:34, 17 September 2009 (EST)

----

Hey all, just need to finish editing the current research part before i post it up, also need to edit some of my images under abnormal development and also references. Should be all done by Monday. --[[User:Z3187802|Vishnnu Shanmugam]] 07:02, 17 September 2009 (EST)

--[[User:S8600021|Mark Hill]] 01:40, 8 September 2009 (EST) OK guys, this is still just a page of text......

--[[User:Z3126328|Jin Lee]] 14:50, 3 September 2009 (EST) I want to make a timeline?

--[[User:S8600021|Mark Hill]] 08:42, 21 August 2009 (EST) z3187802 has contacted me and has been away sick. He should still complete his components of the group project.

Our group is Sum, Vishnnu, Juliana and Jenny. Today in the lab we have decided to research the RABBIT! [http://embryology.med.unsw.edu.au/OtherEmb/Rabbit.htm/ Rabbit embryology from Mark Hill]

(Juliana's email belebele85@msn.com)

----
This is apparently what we need to include in our case study:
#Timeline of Embryo Development - how long (SUM)
#Staging - are there species specific staging, what occurs when (SUM)
#History of Model Use - when was it first used, (JULIANNA)
#Genetics - chromosome number, sequencing (JENNY)
#Abnormal Development (VISHNNU)
#Current Embryology Research - research papers and findings (VISHNNU)

Hey guys, maybe we should add a section comparing rabbit to human development
--[[User:Z3185685|Sumaiya Rahman]] 16:45, 6 August 2009 (EST)

That sounds like a good idea Sum....seeing that human development is the primary theme of the course, not including it would be criminal!. -vishnnu

Report:
* Links to resources and discussions are to be posted on the group talk page, the project page is for the actual assignment
* Final assignment will be marked by another group and everyone will be given a marking criteria
* No information should be obtained from Wikipedia and all information (tables & graphs included) must be referenced
* Please feel free to suggest any further topics which can be included

== Research: ==
So i think the main rabbit used in research is the oryctolagus cuniculus. Lets focus mostly on that (or at least i, Jenny, will since im going genetics). This link is great for the specific genetics: [http://www.ncbi.nlm.nih.gov/nuccore/AJ001588/ Oryctolagus cuniculus complete mitochondrial genome]

Here's some stuff about benefits of modeling from a textbook. I haven't yet written as my own so its still the authors material. Just thought it might benefit us all (and raise our morale as we thought the rabbit might suck..but it doesn't!) We're not "submitting" this as our own work so technically we're not yet copyrighting their material.
Ive cited the book here and the website i got it from:
[http://books.google.com.au/books?id=RY0rXE2HgqsC&pg=PA344&lpg=PA344&dq=rabbit+embryology+genetics&source=bl&ots=rbr3CuBRxY&sig=p8055w9oYQmsQeuN78mgXBGmRK4&hl=en&ei=NI2KStaQJIvSsQOEpMjEDQ&sa=X&oi=book_result&ct=result&resnum=3#v=onepage&q=&f=false/ Cibelli, J., Lanza, R., Campbell, K. and West, M. 2002. Principles of Cloning. Academic Press]

“Rabbits were one of the first species in which blastomere nuclear transfer succeeded; as a model species, rabbits placed a central role in developing the micromanipulation technologies in embryos.” Other advantages for using rabbits are:

# “The costs to animal procurement, animal care, and oocyte production in rabbits are relatively low compared to large animals.” e.g. a cow embryo is 30x more expensive that a rabbit embryo
# “The developmental biology of rabbit embryos and fetuses resembles more closely that of large farm animals than that of rodent model species, including the transition from maternal to embryonic control of embryo development.”
# “The pregnancy of rabbits is relatively short (1 month), allowing rapid evaluation of fetal and postnatal development. In comparison, the gestation length for cattle is 9x longer.”
# “The sizeable milk production of rabbits allows their use as test animals for therapeutic protein expression in milk, or as a living bioreactor.”
# “Rabbits are induced ovulators. Domesticated rabbits are nonseasonal breeders and produce multiple offspring in one litter. These reproductive patterns make the use of rabbits for reproductive research highly efficient.”

----
Here are some links i (sum) found which may help. Need to go through all the info and sort it out, But there are a couple of good diagrams.

'''Links for group assignment'''

http://www.reproduction-online.org/cgi/reprint/48/1/43

http://books.google.com/books?id=RY0rXE2HgqsC&pg=PA344&dq=rabbit+embryo+stages&as_brr=3#v=onepage&q=rabbit%20embryo%20stages&f=false - good for what studies in rabbit embryo have been used for. And has a good table for embryological stages!!

http://books.google.com/books?id=ljAKtC-iIrIC&pg=PA264&dq=rabbit+embryo+stages&as_brr=3#v=onepage&q=rabbit%20embryo%20stages&f=false

http://books.google.com/books?id=73bbKzqRvLsC&pg=PA156&dq=rabbit+embryo+stages&lr=&as_brr=3#v=onepage&q=rabbit%20embryo%20stages&f=false - picture of implantation

http://books.google.com/books?id=aZ7DQYFyxswC&pg=PA122&dq=%22rabbit+development+stages%22&lr=&as_brr=3#v=onepage&q=&f=false
-------
Hi I(Juliana) uploaded file, you guys can have a look.
Go to 'Upload File' tab and click ' early growth of rabbit trophoblast' file.

-------------
also I found an interesting article!
'''An Electron Microscope Study of the Embryology of the Intercalated Disc in the Heart of the Rabbit'''
Alan R. Muir
The Journal of Biophysical and Biochemical Cytology, Vol. 3, No. 2 (Mar. 25, 1957), pp. 193-202
Published by: The Rockefeller University Press

http://info.library.unsw.edu.au/cgi-bin/local/access/ej-access.cgi?url=http://links.jstor.org/sici?origin=sfx%3Asfx&sici=0095-9901(1957)3%3A2%3C193%3AAEMSOT%3E2.0.CO%3B2-S
--

[[User:Z3126328|Jin Lee]] 10:48, 25 August 2009 (EST)

----------------
I found helpful book in the library
'''Bensley's Practical Anatomy of the Rabbit 8thE by E.Horne Craigie, Toronto, University of Toronto Press 1948'''
--[[User:Z3126328|Jin Lee]] 13:27, 27 August 2009 (EST)

==Vishnnu's Research==

'''Background reading (Vishnnu)'''

Hey everyone. I'm starting my background reading section where I shall describe my research resources. They contain a summary and a link to the resource itself. I shall keep this "notes" section updated with each new entry I add.

'''Notes:'''

*Articles 1 & 2 - Juliana this could be useful to you.

*Article 2 - Sum this could be useful to you.

*Articles 3 & 4 - Abnormal development articles (added: 02/09/2009)

*Articles 5 & 6 - Abnormal development articles (added: 13/09/2009)

'''Article 1'''

'''The rabbit as a model for reproductive and developmental toxicity studies''' --[[User:Z3187802|Vishnnu Shanmugam]] 21:05, 30 August 2009 (EST)

''Robert H. Foote and Edward W. Carney'' ''Reproductive Toxicology 14 (2000) 477–493'' ''Department of Animal Science, Cornell University, 204 Morrison Hall, Ithaca, New York 14853-4801, USA Developmental and Reproductive Toxicology, ''The Dow Chemical Company Midland, Michigan 48674, USA''

'''Summary'''

This is a review article of a study looking at the use of rabbits in toxicological studies. The article describes the advantages in using the rabbit experimental model as opposed to the rodent model (mice & rats) and outlines the differences that make toxicological studies on rabbit embryos more accurate than rodents to resemble similar toxicological effects in human embryos. The article describes various techniques that can be used (eg. blood collection from marginal ear vein, artificial insemination, embryo collection) and solutions to some common problems that researchers face when using animal models. Very interesting article with a great quote from Robert Koch to open the eyes of researchers to other animal models:

“Gentlemen, never forget that mice are not human beings”

Want to find out more? Follow the link!

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6TC0-41SBGDH-1&_user=37161&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_acct=C000004218&_version=1&_urlVersion=0&_userid=37161&md5=4db60dc9352996fc4865b9d781b0128d

'''Article 2'''

'''Developmental stages in the rabbit embryo: guidelines to choose an appropriate experimental model''' --[[User:Z3187802|Vishnnu Shanmugam]] 21:05, 30 August 2009 (EST)

''S. Beaudoin; P. Barbet; F. Bargy''
''Fetal Diagnosis and Therapy; Nov/Dec 2003; 18, 6; Academic Research Library''
''pg. 422''

'''Summary'''

The article describes the various stages in the developing rabbit embryo and the rationale for using rabbits to study normal and abnormal embryology. The article details normal developments in the rabbit embryo and compares it to the developing human embryo. By making this comparison the article argues for the validity of rabbit embryology to better understand human embryology and also suggests that due to the similarities in the developing rabbit and human embryos, experiments on rabbit embryo’s yield more reliable results for human embryology. The article has some rare images on normally developing rabbits and breaks the developmental stages down (in days) describing the observable characteristics that form (eg. Limb development & body formation).
I have decided to use the image provided in the journal.

Definitely worth reading people, follow the link!

http://content.karger.com/produktedb/produkte.asp?typ=fulltext&file=FDT2003018006422

'''Article 3'''

'''Acheiropodia is caused by a genomic deletion in C7orf2, the human orthologue of the Lmbr1 gene''' --[[User:Z3187802|Vishnnu Shanmugam]] 04:32, 2 September 2009 (EST)

''P. Ianakiev, M. J. van Baren, M. J. Daly, S. P. A. Toledo, M. G. Cavalcanti, J. Correa Neto, E. Lemos Silveira, A. Freire-Maia, P. Heutink, M. W. Kilpatrick, P. Tsipouras''
''Am. J. Hum. Genet. 68:38–45, 2001''
''Department of Pediatrics, University of Connecticut Health Center, Farmington, CT;''
''Department of Clinical Genetics, Erasmus University, Rotterdam;''
''Whitehead Institute for Biomedical Research, Cambridge, MA;''
''LIM/25-D, University of Sao Paulo School of Medicine,''
''And Private Practice, Sao Paulo;''
''Private Practice, Porto Alegre, Brazil;''
''Department of Genetics, UNESP-Universidade Estadual Paulista, Botucatu SP, Brazil''

'''Summary'''

The article describes the developmental abnormality Acheiropodia can be passed down genetically from parent to offspring. Acheiropodia (also known as Horn Kolb Syndrome) is a condition where the distal extremities of the embryo fail to form. Although it is not fatal, the individual endures a very difficult life without hands and feet. The article notes that the disorder only affects the development of the limbs and has no other reported manifestations. The article defines this to be an autosomal recessive disorder which means that two copies of an abnormal gene must be present in the affected individual in order for the disease to develop. Thus, each parent passes an abnormal gene to the offspring. It is interesting to note the process of the malformation from genotype to phenotype: small deletions on the chromosomes produce abnormal genes, the abnormal genes are then passed down to the offspring, the offspring that inherits two of the abnormal genes is unable to code for the correct proteins and as a result, there is failure in normal development of limb extremities in the embryo phenotype. The article also has a shocking image of an individual with Acheiropodia which highlights the extent to which it can impact a person’s life and the urgent need to find a cure.

Read more about the exact nature of the abnormal gene using the link.

http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=1109034

'''Article 4'''

'''Epidemiology of congenital clefts of the lip and palate''' --[[User:Z3187802|Vishnnu Shanmugam]] 04:32, 2 September 2009 (EST)

''JOHN C. GREENE'' ''D.M.D. ,M.P.H.'' ''Public Health Rep. 1963 July; 78(7): 589–602''

'''Summary'''

This review article combines research to study the factors causing the developmental abnormalities cleft palate and cleft lip in populations. “Cleft palate (palatoschisis)” and “cleft lip (cheiloschisis)” are the terms used to describe the non- fusion of the upper lip, hard or soft palate and typically occur during the gestation phase of embryonic development. The article tables the occurrence of cleft palate and cleft lip in populations of people in various cities across the world. It also compares the occurrence of cleft palate and cleft lip in males and females. The article finds that the incidence of cleft palate and cleft lip is:

*Is random in males and females (ie. Occurs approximately evenly in both sexes)

*Is random in people living in different cities

*Is higher in children of mothers over the age of 35

*Is higher in white populations and lower in the negro populations which suggests possible role of environmental factors

*No concrete proof that cleft palate and cleft lip is hereditary

*Is higher in rats exposed to radiation and those fed riboflavin

*Is higher in rabbits and other lab animals exposed to higher stress through cortisone injections

Although the article is now quite ancient, it is interesting to note the incidence of cleft palate and cleft lip among people. It also shows the historical foundation of research into the causes of cleft palate and cleft lip through animal experimentation.

Read more about cleft palate epidemiology using the link.

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1915191

'''Article 5'''

'''Chromosome abnormalities in human embryos''' --[[User:Z3187802|Vishnnu Shanmugam]] 00:10, 13 September 2009 (EST)

''Santiago Munne & Jaques Cohen The Center for Reproductive Medicine and science of Saint Barnabas Medical Center, New Jersey, USA Human Reproductive Update 1998, Vol. 4, No. 6 pp. 842-855 European Society of Human Reproduction and Embryology''

'''Summary'''

As the title suggests, this article focuses on chromosomal abnormalities in the developing human embryo. To understand this article, it is necessary to first establish some basic definitions that are used throughout the article. Aneuploidy can be defined as the occurrence of one or more extra or missing chromosomes leading to an unbalanced chromosome number. Although most babies with an unbalanced amount of chromosomal material miscarry during the first trimester of pregnancy, those that are born have crippling conditions such as:

* Birth defects

* Turner's syndrome (disorder where a female child is born with only 1 X chromosome)

* Down's syndrome (disorder where child is born with 3 copies of chromosome 21)

* Edward's syndrome (disorder where child is born with 3 copies of chromosome 18)

* Patau's syndrome (disorder where child is born with 3 copies of chromosome 13)

* Klinefelter's syndrome (disorder where male child is born with 2 copies of the X chromosome and 1 Y chromosome)

Polyploidy is a type of aneuploidy where the baby has three, four, or more sets of chromosomes instead of the two present in diploids. Chromosomal mosaicism is when different cells within an individual, who has developed from a single fertilized egg, have a different chromosomal makeup. Most commonly there will be some cells with a typical number of chromosomes (46 chromosomes) and other cells with an altered number or structure of chromosomes.

The article explores the possible causes of chromosomal abnormalities resulting from pregnancy though techniques such as IVF (In-Vitro Fertilization) and ICSI (Intracytoplasmic Sperm Injection). It also analyses the role of FSH (follicle stimulation hormone), temperature, water and light in chromosomal abnormalities.

The article finds:

* High FSH concentration increases likelihood of chromosomal abnormalities

* ICSI & IVF techniques have increased likelihood of chromosomal abnormalities

* Chromosomes exhibit temperature sensitivity and changes in temperature can cause chromosomal abnormalities

Although the article makes a number of findings, it is yet to be backed up with convincing evidence; the article has some really cool images of the developing embryo soon after fertilization. Overall, an interesting read.

Interested? Follow the link!

http://humupd.oxfordjournals.org/cgi/reprint/4/6/842.pdf

'''Article 6'''

'''Evaluation of the Safety and Pharmacokinetics of the Multi-Targeted Receptor Tyrosine Kinase Inhibitor Sunitinib During Embryo–Fetal Development in Rats and Rabbits''' --[[User:Z3187802|Vishnnu Shanmugam]] 00:10, 13 September 2009 (EST)

''S. Patyna, J. Haznedar, D. Morris, K. Freshwater, G. Peng, J. Sukbuntherng, G. Chmielewski, and D. Matsumoto''
''Pfizer Global Research and Development, San Diego, California''
''Roche LLC, Palo Alto, California''
''Pfizer Global Research and Development, Kalamazoo, Michigan''
''Xenoport Inc., Santa Clara, California''
''Pfizer Global Research and Development,'' ''Groton, Connecticut '' ''Birth Defects Research (Part B) 86:204–213 (2009)''

'''Summary'''

The article looks at how toxicity affects embryo-fetal development. The article describes the abnormal changes that occur when Sunitinib (an oral inhibitor of multiple receptor tyrosine kinases) is administered to pregnant rabbits and rats. This experiment was performed in an attempt to mirror the effects of antiangiogenic agents used in cancer treatment. Sunitinib is an antiangiogenic agent and the use of antiangiogenic agents is not recommended for treating cancer in pregnant patients because of the potential harm to embryo-fetal development. Angiogenesis (the formation of blood vessels) plays a critical role in embryo–fetal development and antiangiogenic agents slow down and/or stop the formation of blood vessels in order to control cancer and stop its spread. In pregnant patients however, this has the potential to adversely affect the developing embryo and these adverse effects is what is investigated in this article.

The article finds the antiangiogenic agent Sunitinib at toxic levels can result in:

* Embryo death

* Fetal skeletal malformations including vertebrae malformation and cleft lip/palate

* Teratogenic effects in rabbits

* Decreased maternal and fetal body weight

This article is a recent study and provides important findings regarding the use of antiangiogenic agents, especially during pregnancy. Although the maternal effects are minimal, the adverse effects to the embryo are significant and permanent. The article makes good use of tables and graphs to juxtapose pieces of information and to show trends. It is very interesting to note the extent to which chemicals can impact the vulnerable developing embryo.

Read more at link. (Use institutional login from UNSW computers)

http://www3.interscience.wiley.com/journal/122262246/abstract?CRETRY=1&SRETRY=0

------
thank you so much Vishnuu~~^^ from Juliana
-----
I also changed the format if you guys dont mind--[[User:Z3126328|Jin Lee]] 18:33, 31 August 2009 (EST)
----

Hey '''Vishnuu''', that link you found with the stages is awesome! thanks so much. Do you know if i am allowed to use the embryo pics in that article on our wiki page?? i'm not sure about the copyright rules. It says at the bottom of the article "Reproduced with permission of the copyright owner. Further reproduction prohibited without permission."
Does this mean we can only provide a link to it on our page? if so that's a shame, because those pics were fantastic!! '''SUM'''

Oh i also added an introduction - sum

Hey Sum,
Unfortunately, since its copyright protected we can't use the image directly......but there is a way of getting around it....You can modify the image using picture editing tools, then simply reference where the original picture came from and state that it has been modified by you. Alternatively, you can trace around the picture and provide only an outline (this will be very difficult to do with detailed pictures, a good picture editing software is recommended). Either way according to whats written under '''editing basics''' we need to include a picture that has been drawn up ourselves in the project. Also, not sure if you are aware, but the project is NOT due on Thursday (3rd September), Dr. Hill has very generously given everyone an extension till after mid-session break. --[[User:Z3187802|Vishnnu Shanmugam]] 02:35, 2 September 2009 (EST)

==Julianna's Research==
[http://netvet.wustl.edu/species/rabbits/rabtmodl.txt]
HISTORY OF THE RABBIT (IN RESEARCH)

A. Discovered in Spain about 100 B.C.
B. Domesticated in the 1500's
C. Standardization of breeds in 1800's
1. Research Uses
a. 1852: Rabbits have DL-hyoscyamine
(a) Can survive belladonna
(b) Endogenous atropine esterase
b. 1884: Pasteur develops rabies vaccine
c. 1891: Heape performs embryo transfer
(a) Influence on phenotype of the
uterine environment
d. 1908: Ignatowsky produces atherosclerosis
(a) Fed diets of milk, meat, and
eggs
(b) Produced intimal lesions
(c) Believed lesions due to protein
e. 1928: Demonstrated intranuclear development
of herpes virus
f. Graafian follicle was first observed
g. Coat colors and Mendelian inheritance
h. Immunology studies
i. Testing of human use products
j. Basic science studies
k. Diagnostic requirements
l. Eye Research
m. Pyrogen testing
n. Fetal drug induced teratology
o. Parasite research

LITERATURE REVIEW OF RABBIT USE

A. 1956 to 1800 ... Over 8000 citations
B. 1966 to 1987 ... 130,000 citations linking the rabbit to
all areas of research
C. 1988 to present ... 821 citations under the search
criteria: Rabbit: Model: Human Disease
D. Numbers of Rabbits Used (APHIS; ILAR records 1989)

1967 504,500
1978 439,986
1982 547,312
1983 466,810
1984 529,101
1985 544,621
1986 521,773
1987 534,385

ADVANTAGES OF USING RABBITS
A. Provides repeatability of animal model studies
B. Large enough for single samples
C. Many stocks/strains as animal models
D. Easily managed
E. Quality of immunologic products
F. Ease of reproductive control

DISADVANTAGES OF USING RABBITS
A. Most colonies are a storehouse of diseases
B. Extremely variable to responses to general anesthetics

[http://www.ncbi.nlm.nih.gov/pubmed/18430597]
The rabbit as a model to study asthma and other lung diseases.Keir S, Page C.
Sackler Institute of Pulmonary Pharmacology, Division of Pharmaceutical Sciences, 5th Floor Hodgkin Building, King's College London, Guy's Campus, London SE1 9RT, UK.

No single animal model is able to reproduce all the features of human asthma. However, the similarities between neonatally immunised rabbits and human asthma highlight the value of this model in the investigation of asthma pathophysiology and in the development of therapeutic agents. Airway inflammation and airway responses to various stimuli including histamine, adenosine 5'monophosphte and antigen in allergic rabbits have shown similarities with the responses observed in asthmatics. Furthermore, functional studies in rabbit airways show they are poorly responsive to capsaicin as are human airways. Chronic pre-treatment with capsaicin desensitises the TRPV(1) receptor enabling studies into the effect of this drug in both rabbits and man. The allergic rabbit model has been used extensively in assessing the various classes of anti-asthma drugs and is sensitive to similar drugs as patients with asthma, including beta-adrenoceptor agonists, corticosteroids, phosphodiesterase inhibitors and theophylline. This article highlights the usefulness of the rabbit as a species to study lung biology.

[http://www.ncbi.nlm.nih.gov/pubmed/8447943]
Effects of strain and embryo transfer model (embryos from one versus two donor does/recipient) on results of cryopreservation in rabbit.Vicente JS, García-Ximénez F.
Departamento de Ciencia Animal, Universidad Politécnica de Valencia, Spain.

Differential effects of 2 transfer models for normal thawed embryos of 1 donor doe were studied on the offspring rate and their embryo survival at birth from 3 selected rabbit strains (SY and SB: synthetic strains, NZ: New Zealand White). Morulae were obtained 64-66 h post-coitum from 93 adult does treated with 25 IU of hCG (SY:36, NZ:27, SB:30). Morphologically normal morulae were frozen in the presence of 1.5M DMSO and stored in liquid nitrogen. Normal thawed embryos were transferred into the oviducts of synchronized recipient does of the same strain 48 h after being injected with 25 IU of hCG (SY:28, NZ:21, SB:24). Each recipient received embryos from 1 (single transfer) or 2 different donor does (double transfer). Significant differences were observed in the post-thawing percentage of normal embryos between strains (SY:95 +/- 1% and SB:85 +/- 3%, P < 0.05; NZ: ,91 +/- 2%). After transfer, no significant differences were observed in pregnancy rate and offspring rate between the transfer models, whereas significant differences were only found in survival rate when all transfers were analyzed (double: 24 +/- 4% vs single: 14 +/- 3%, P < 0.05). An effect of strain was detected in the pregnancy rate (NZ: 33% vs SB: 71%, P < 0.05; SY: 61%) and in the survival rate per donor doe on pregnant recipient doe (SY: 42 +/- 5 vs SB: 19 +/- 5, P < 0.05; NZ: 34 +/- 7%). These results suggest a differential embryo sensitivity with respect to their genetic origin in both the freezing-thawing and transfer procedures.

--[[User:Z3126328|Jin Lee]] 13:06, 3 September 2009 (EST)

[http://www.ncbi.nlm.nih.gov/pubmed/14064965?log$=activity]GROSS EFFECTS ON RABBIT EMBRYOS AND MEMBRANES OF X-IRRADIATION IN THE BLASTOCYST STAGE.

[http://www.ncbi.nlm.nih.gov/pubmed/11139224?ordinalpos=408&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum]Onset of zygotic transcription and maternal transcript legacy in the rabbit embryo.Brunet-Simon A, Henrion G, Renard JP, Duranthon V.
Laboratoire de Biologie du Développement, INRA, Jouy en Josas Cedex, France.

Onset of zygotic transcription is progressive from the one-cell stage onward in the rabbit embryo. Maternal transcripts remain fairly stable until the 8-16 cell stage when major transcriptional activation of the zygotic genome takes place. To understand the mechanisms of the maternal-to-zygotic transition in the genetic information governing development, we asked whether a progressive synthesis of zygotic transcripts takes over the maternal molecules, or whether the synthesis of zygotic transcripts is very abrupt and independent of the persistence of the maternal counterparts. To answer this question, we set up mRNA differential display experiments comparing the mRNA content of rabbit embryos at different stages during the preimplantation period. We isolated eight zygotic transcripts whose synthesis is abruptly turned on at the 8-16 cell stage. These transcripts are involved in general cellular metabolism and their maternal counterparts are still present up to the four-cell and even the 8-16 cell stage. This identification of early zygotic transcripts suggests that global long range modifications of chromatin structure result in a rapid increase in transcription rates during the major transcriptional activation of the zygotic genome.

[http://www.ncbi.nlm.nih.gov/pubmed/11245264?ordinalpos=409&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum]
Reconstruction of the heteroparental diploid condition in rabbit zygotes by nuclear transfer.Escribá MJ, García-Ximénez F.
Departamento de Ciencia Animal Universidad Politécnica de Valencia, Spain. mescriba@dca.upv.es

Studies on genomic imprinting showed that parental genomes have complementary roles during embryogenesis, are both essential and need to be synchronized in their embryonic stage for successful development to term. To our knowledge, these studies have not been performed in species other than mice. We studied the in vitro and in vivo development of reconstructed zygotes by combining female haploid nuclear donors and androgenetic hemizygous recipients. Haploid donor embryos at the 8- or 32-cell stage were obtained from electroactivated young rabbit ova (eight pulses maximum, consisting of 0 6 kVcm(-1) for 60 microsec each, 38 min apart) which were further cultured for 24 h or 32 h. Couplets formed by both the haploid male hemizygous recipients and haploid female donor cells were electrofused (2.2 kVcm(-1) for 60 microsec duration each, 30 min apart) and their nuclear configuration determined 122 of those fused (43%: 122/286) were diploid. Reconstructed diploid zygotes developed in vitro up to the compacted morula, blastocyst and hatched stages (1/8-nuclei x 50%, 18% and 9% vs. 1/32-nuclei: 47%, 25% and 19%; P > 0.05), respectively. In embryo transfer assays, both 1/32-reconstructed zygotes and control, non-manipulated zygotes were transferred to synchronized does Four live reconstructed fetuses (4/49: 8 1% survival rate) and five in regression stage (9/49: 18% implantation rate) were observed on Day 21 post-ovulation, whereas from control zygotes, 11 fetuses were alive (11/53 21% fetal survival rate) and 2 degenerated (13/53 x 24 5% implantation rate). Similar results were obtained from a final experiment, in which development was allowed to progress to term. Six live rabbit pups derived front experimentally reconstructed zygotes (11%; 6/54) and three fetuses in regression stage were obtained; values slightly lower than those derived from non-manipulated and transferred control zygotes (18% 9/50, live born rate).

[http://www.ncbi.nlm.nih.gov/pubmed/11589623?ordinalpos=412&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum]
Effects of leukaemia inhibitory factor on endometrial receptivity and its hormonal regulation in rabbits.Liu CQ, Yuan Y, Wang ZX.
Shanghai Institute of Planned Parenthood Research, Shanghai, P. R. China.

The effects of hormones on production of leukaemia inhibitory factor (LIF) and the uterine receptivity in rabbits were studied. In ovariectomised rabbits, LIF protein was not detected in control but upregulated by progesterone alone. Oestrogen had a slightly negative effect when the rabbits were treated with both oestrogen and progesterone. Mifepristone (Mi) inhibited the progesterone-stimulated production of LIF in rabbit uterus. The transfer of embryos to LIF-treated recipients significantly increased pregnancy rate (70%) and implantation rate (27%) as compared with control (pregnancy rate=40% and implantation rate=17%). The transfer of embryos to LIF and mifepristone-treated recipients significantly decreased pregnancy rate (30%) and implantation rate (9%). The results indicated that LIF protein had a beneficial effect on uterine receptivity and mifepristone prevented this effect. Copyright 2001 Academic Press.

[http://www.ncbi.nlm.nih.gov/pubmed/8447943]
Effects of strain and embryo transfer model (embryos from one versus two donor does/recipient) on results of cryopreservation in rabbit.Vicente JS, García-Ximénez F.
Departamento de Ciencia Animal, Universidad Politécnica de Valencia, Spain.

Differential effects of 2 transfer models for normal thawed embryos of 1 donor doe were studied on the offspring rate and their embryo survival at birth from 3 selected rabbit strains (SY and SB: synthetic strains, NZ: New Zealand White). Morulae were obtained 64-66 h post-coitum from 93 adult does treated with 25 IU of hCG (SY:36, NZ:27, SB:30). Morphologically normal morulae were frozen in the presence of 1.5M DMSO and stored in liquid nitrogen. Normal thawed embryos were transferred into the oviducts of synchronized recipient does of the same strain 48 h after being injected with 25 IU of hCG (SY:28, NZ:21, SB:24). Each recipient received embryos from 1 (single transfer) or 2 different donor does (double transfer). Significant differences were observed in the post-thawing percentage of normal embryos between strains (SY:95 +/- 1% and SB:85 +/- 3%, P < 0.05; NZ: ,91 +/- 2%). After transfer, no significant differences were observed in pregnancy rate and offspring rate between the transfer models, whereas significant differences were only found in survival rate when all transfers were analyzed (double: 24 +/- 4% vs single: 14 +/- 3%, P < 0.05). An effect of strain was detected in the pregnancy rate (NZ: 33% vs SB: 71%, P < 0.05; SY: 61%) and in the survival rate per donor doe on pregnant recipient doe (SY: 42 +/- 5 vs SB: 19 +/- 5, P < 0.05; NZ: 34 +/- 7%). These results suggest a differential embryo sensitivity with respect to their genetic origin in both the freezing-thawing and transfer procedures.

[http://www.ncbi.nlm.nih.gov/pubmed/14564113]
'''Developmental stages in the rabbit embryo: guidelines to choose an appropriate experimental model.'''Beaudoin S, Barbet P, Bargy F.
Department of Pediatric Surgery, Groupe Hospitalier Cochin-Saint-Vincent de Paul, Paris, France. sylvie.beaudoine@svp.ap-hop-paris.fr

Researchers involved in the field of congenital malformations are often forced to work on an animal model. Both accurate description of its normal development and comparative staging with human development will be mandatory. To complete the lacking medical literature, we herein provide such data for the rabbit model. Sampled rabbit embryos were staged using the Carnegie criteria, in order first to determine if they were consistent with the rabbit developmental pattern, and second to compare this pattern with the human one. Our results show a suitable comparison of rabbits and humans in early developmental stages, except for the neural growth. Copyright 2003 S. Karger AG, Basel

Z3185685

2009-10-08T04:35:57Z

Z3185685:

== '''Lab 1 Questions''' ==

1)What is the protein that sperm binds to on the surface?
ZP3

2)Name the 3 stages of follicle development in the ovary.

- Primordial follicle
- Preantral follicle
- Antral follicle (Graafian)

----

--[[User:Z3185685|Sumaiya Rahman]] 13:08, 6 August 2009 (EST)
== '''Lab 2 Questions''' ==

1. What factor do the synctiotrophoblast cells secrete to support the ongoing pregnancy?

Human Chorionic Gonadotropin (hCG)

2. What does the corpus luteum secrete to prevent continuation of the menstrual cycle?

Progesterone

3. What are the 2 main tissues to be derived from the germ cell layer continuous with the lining of the amniotic sac?

Nervous tissue and epithelium of the skin

----
'''Links for group assignment'''

http://www.reproduction-online.org/cgi/reprint/48/1/43

http://books.google.com/books?id=RY0rXE2HgqsC&pg=PA344&dq=rabbit+embryo+stages&as_brr=3#v=onepage&q=rabbit%20embryo%20stages&f=false - good for what studies in rabbit embryo has been used for. And has a good table for embryological stages!!

http://books.google.com/books?id=ljAKtC-iIrIC&pg=PA264&dq=rabbit+embryo+stages&as_brr=3#v=onepage&q=rabbit%20embryo%20stages&f=false

http://books.google.com/books?id=73bbKzqRvLsC&pg=PA156&dq=rabbit+embryo+stages&lr=&as_brr=3#v=onepage&q=rabbit%20embryo%20stages&f=false - picture of implantation

http://books.google.com/books?id=aZ7DQYFyxswC&pg=PA122&dq=%22rabbit+development+stages%22&lr=&as_brr=3#v=onepage&q=&f=false

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--[[User:Z3185685|Sumaiya Rahman]] 13:14, 13 August 2009 (EST)
== '''Lab 3 Questions''' ==

1. What period of human development (in weeks) do the 23 Carnegie stages cover? 8 weeks

2. What part of the somite will contribute to the vertebral column? The ventromedial component - sclerotome

3. At what Carnegie stage does the human neural tube normally completely close? Stage 13

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--[[User:Z3185685|Sumaiya Rahman]] 13:57, 20 August 2009 (EST)
== '''Lab 4 Questions''' ==

1. Into what structure do most blood vessels empty before they enter the embryonic heart? The liver

2. What do the dorsal aortas become in the adult? The descending aorta

3. What are the layers of cells found in a tertiary villi?

----

--[[User:Z3185685|Sumaiya Rahman]] 14:13, 27 August 2009 (EST)
== '''Lab 5 Questions''' ==

1. What was the question I said in the respiratory lecture would be part of this week's assessment?

Is it more common for a congenital diaphragmatic hernia to happen on one side or both?

2. What is the answer to the above question?

It is more common for a diaphragmatic hernia to occur on one side. Majority (80%) occur on the left side.

----

--[[User:Z3185685|Sumaiya Rahman]] 13:59, 3 September 2009 (EST)

== '''Lab 6 Questions''' ==

1. Which is the more common clefting, cleft lip or cleft palate? Cleft lip is more common

2. What structures does pharyngeal pouch 1 form? tympanic membrane, tympanic cavity, mastoid antrum, auditory tube

3. Neural crest forms which cells within the skin? melanocytes

http://www.reproduction-online.org/cgi/reprint/125/4/479
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2694706

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--[[User:Z3185685|Sumaiya Rahman]] 13:46, 17 September 2009 (EST)

== '''Lab 7 Questions''' ==

1. Briefly; what is a myotube and how is it formed?
- Elongated mulitinucleated cells that have peripherally located myofibrils.
- They are formed by a fusion of myoblasts during skeletal development and eventually develop into mature muscle fibres.

2. What changes would I expect to see in the muscle fibre types in my legs if I:

a) Suffered a spinal cord injury
-Muscle atrophy
-conversion of slow twitch muscle fibres to fast twitch muscle fibres.

b) Took up marathon running
-Conversion of fast twitch muscle fibres to slow twitch muscle fibres
----

--[[User:Z3185685|Sumaiya Rahman]] 13:32, 24 September 2009 (EST)

--[[User:Z3185685|Sumaiya Rahman]] 13:21, 1 October 2009 (EST)

== '''Lab 10 Questions''' ==

--[[User:Z3185685|Sumaiya Rahman]] 15:35, 8 October 2009 (EST)

Talk:2009 Group Project 1

2009-10-08T04:31:07Z

Z3185685: /* Things to work on noted by peers */

== Lab 10 ==
--[[User:Z3283499|Antonio Lee]] 10:52, 2 October 2009 (EST) Hi everyone, I will be working with you during the Lab10 Tutorial and here is the news link and PDF of the manuscript for your group exercise. I encourage you to read the paper before the tutorial. Also, please indicate next to the questions below (using either your initials or student number) which one of the four questions you wish to address.
:'''Group 1 :''' [http://www.nature.com/nature/journal/v461/n7262/full/461354a.html '''Developmental biology: Asexual healing'''] in Nature News and Views - Nature 461, 354-355 (17 September 2009) [[Media:ANAT2341_Lab10_2009_Group 1 Reading.pdf|Manuscript (PDF): Mitochondrial gene replacement in primate offspring and embryonic stem cells]]

:Question 1. What is the background to the existing problem / disease condition? --[[User:Z3187802|Vishnnu Shanmugam]] 22:12, 2 October 2009 (EST)
:Question 2. What approach / method did the research team take to tackle / improve the problem?--[[User:Z3126328|Jin Lee]] 12:31, 7 October 2009 (EST)
:Working with rhesus macaque monkeys, the authors reconstructed mature oocytes containing the nuclear genome from one oocyte and the mitochondrial genome from another. To do this they removed the nuclear genetic material from one oocyte, leaving behind all of the mitochondrial DNA, then transferred it to another oocyte whose nucleus had been removed (a cytoplast), but which contained a full complement of mitochondrial DNA.
:Question 3. What was the breakthrough / major advancement OR failure / drawback? and why might this be of significance?
::Drawbacks - --[[User:Z3186093|Jenny Guy]] 22:43, 7 October 2009 (EST)
:::There were difficulties in visualising and isolating the intact chromosomes, as well as the mtDNA being susceptible to damage and translocation/movement. Visualization became easier after the development of techniques for DNA staining with fluorophores and looking under UV light during embryo cloning by the SCNT (somatic cell nuclear transfer). Successful implementation to avoid damage to the cytoplast during spindle removal involved using polarized microscopy. (p368) --[[User:Z3186093|Jenny Guy]] 14:12, 8 October 2009 (EST)
:Question 4. What are the next steps in moving forward? What are the next or new hurdles to overcome?

==Actual Changes Made==
--[[User:Z3187802|Vishnnu Shanmugam]] 20:22, 7 October 2009 (EST) Hey gang. By popular demand (or the stress of reading) people want less text. I have removed the entire cleft palate & cleft lip section from abnormal development. For current research, I have also created a step by step picture guide for transgenic rabbit creation. It was initially meant to be a video, but this wiki page does not display (.gif) or (.mov) files. Sum, I remember that you did your references after me...so when I removed the cleft palate & cleft lip section, the references changed....so I have also adjusted your references accordingly. I don't think it is necessary to make all the changes outlined below as most comments are subjective (different people have different preferences) and seems like some comments were made because people had nothing else to propose.

--[[User:Z3126328|Jin Lee]] 10:01, 8 October 2009 (EST)Hi Guys, I have fixed spelling mistake and some people commented to make table form for advantages and disvantages section. But I liked the way I presented so I will leave in point form.

--[[User:Z3186093|Jenny Guy]] 14:32, 8 October 2009 (EST)
Hey! I looked at what i could change in the genetics section and decided to format a little. Our peers asked:
* genome information into a table - this is a little silly since there'd only be one column.
* Reformating in sections such as hitory and genetics. - have tried to do a little.
* Make pictures appear on the same side of page. maybe aligning the pics on either the left or right side instead of both left and right, and possibly putting them as thumbnails could also work. - i tried to put both of the chromosome images ont he same side (tried both left and right) but found that it looked terrible considering the size (which is needed to see it) as the text wouldnt fit around it very well.
* it will look much better if there is some work to be done for the structure of it especially the paragraph under the heading of 'abnormalities'. - am still in the process. not sure what else i can do since its in basic dot point form with not a large text to format. any ideas? or shall i leave it how it is now?
* maybe instead of writing the entire reference, you could just state The Broad Institute or just the people related to it - i feel that the entire team needs a mention since all people relate to it. noting just the broad institute is almost like noting a team of people here in unsw as just plainly "UNSW" which is just disrespectful.

==Things to work on noted by peers==

Hey, So the changes i will make will be in the introduction section. Also a lot of people have said to add pictures in the stages section to make it more interesting. I couldnt get permission to use the images so i bought tracing paper today! lol will try to draw them and see if they are ok enough to add. I think i am going to leave the timeline section as is because most people liked it. What do u guys think? --[[User:Z3185685|Sumaiya Rahman]] 15:31, 8 October 2009 (EST)

Hey guys,
I read through all the notes our peers have given us and summarised them into the following sections. Majority of them overlap (where ive put a new persons opinions in the same dot point over and over to stress the point on how many people noticed). Some things are easily changed, most of all i reckon its
# formatting
# pictures
# text to be more concise
So we just need to finalise all these minor things to improve our project. Please detail any changes you've made in the the heading above.
Cheers, --[[User:Z3186093|Jenny Guy]] 20:30, 7 October 2009 (EST)

INTRODUCTION
* a little too brief, more information needed
* For the first sentence (the characteristics that make the rabbit an excellent model for study), mention the section 'Why are we using rabbits?' under History section.
* For the second sentence (study that developed and improved micromanipulation techniques), mention the 'Transgenic Rabbit' section below under the genetics section. I've read the entire project page, and the introduction was the only place I found that was not precise enough (which is a great thing). These are minor things, but I think they will help with improving your project page.
*suggestion: Place the history section after the Introduction. This gives the viewer an overview of the use of the rabbit embryo. This way the viewer is first subjected to a few examples of the rabbit embryos use. It also allows him/her to understand where the rabbit embryo sits in with history. I guess this is a matter of personal preference.

HISTORY
* The advantages and Disadvantages would be better in a table. the history you might want to put the advantages and disadvantages into a table to make the page look a bit more tidy and easier to read when we go through it.
* The usage of rabbits for experimental models in science and medicine could be stated under the history section to allow background information for the readers to become aware of the topic and why the rabbit have been used to study specfic medical procedures and diseases.
* Spelling mistake under 'Discovery of Graafian Follicle', 2nd paragraph. I think it's previous instead of 'previcous'.
* Reformating in sections such as hitory and genetics. Make pictures appear on the same side of page.
* The history section can be improved if the infomation is expanded to give some more detailed background knowledge although i like the idea that the information is concise describing each scientists contribution towards the model.
* could be formatted to make the information stand out and a lot more appealing, I would recommend including pictures if possible that link to the text and making the advantages and disadvantages into a table rather than listing it.

TIMELINE
* more images to wholly understand. timeline/staging section was clear and concise, however it could be improved by adding more colour/pictures to maintain the readers' interest. The timeline and staging bits are very well written and clear but i think you should add a few images in there to match up with the text. Perhaps some pictures of embryos throughout development. Pictures for every stage would make it more visually attractive rather than just reading text. lack of pics in the timeline.
* It’s a little confusing that the development jumps back and forth according to the body part developing. Maybe it should be categorised according to time of development instead for greater clarity at first glance
* The timeline is just a little confusing, as its divided into development of different parts, which breaks the time flow.
* some of the information for the timeline section was too heavy for the page - would recommend only using some of the information on your actual page and having the rest as links to separate pages

STAGING
* pictures for stages would have been nice, unless there were none????
* a more even distribution of information, particularly more detail in the stages
* Provide pictures for individual stages. Get visual, and make the stages interesting to read. include pictures in the stages section.
* Staging section is also very well presented but the information presented in a table would even look better if there is use of some pictures to make it more interesting for its audience.
* staging section was very bland and would be more appealing with pictures. I dont think its necessary to cite your entire reference within the text

GENETICS
* genome information into a table
* Reformating in sections such as hitory and genetics.
* Make pictures appear on the same side of page. maybe aligning the pics on either the left or right side instead of both left and right, and possibly putting them as thumbnails could also work.
* it will look much better if there is some work to be done for the structure of it especially the paragraph under the heading of 'abnormalities'.
* maybe instead of writing the entire reference, you could just state The Broad Institute or just the people related to it

ABNORMAL DEVELOPMENT
* There is also a lot of content which might be alleviated by reducing the section on abnormal development. Too much information about the abnormalities. make more concise.
* the abnormalities went a bit over board, and didn't need that much attention I think (as compared witht the research which was good)
* reduce the writing content. for example. In the current research section, you have two scientific process of transgenic rabbits as well as cloning which is described in how these are done. why not draw a step by step diagram, and put these written steps in the link to the image.
* The information provided under Hydrocephalus and Brachydactylia was informative and interesting, but it contained too much text. I suggest you narrow it down and make use of Dots point, numbering, bold/italic words, and/or sub-sub-headings.
* Section for "Abnormal Development" gives the readers useful amount of information but i think its very lenghty, use of dot points can make it look even better and easy to understand.

CURRENT RESEARCH
* the group makes good usage of diagrams but towards the end diagrams die out, you might want to make the current research part of your assignment into diagrams and steps as there is just a bunch of information thrown there and alot of reading needed, if you put it into steps or diagrams it will make the marking process and reading process easier and allow us as reader to understand the information with ease.
* 'Transgenic Rabbit' should be shifted toward the genetic information on the rabbit. (Jenny - i dont agree with this as its research, not its offical genetics. Vishnnu - Neither do I)
* information in regard to stem cells should be brief and truncated. Example in regard to stem cell research should have brief and simple model explaining the process and why it used.
* There is too much information under stem cells. There is 2 examples of studies dealing with stem cells. A suggestion would be to just have one, and have a link saying 'Koga's research on Stem Cells'.
* Have the section 'links to Research labs and researchers' placed at the end of current research. That way, the information on the page will flow smoother.
* more of a focus on current research i.e. what each method is being used for and less on the process behind each method.
* great amount of information but in my perspective replacing the paragraphs with some dot points with heading and subheadings would further enrich understanding of readers.

OVERALL
* "As you start going down the page though the information starts to read a bit haphazardly, for example the developing body; jumping for section to section and the timeline section. it would be great if you could clean this up as it doesn't really flow." - formatting
* condense long slabs of text as the page is long
* format it so there are no huge gaps
* move the links to current research labs up closer to the current research section, just to keep it all together

==Constructive Criticism of Coordinator==
--[[User:S8600021|Mark Hill]] 08:07, 8 October 2009 (EST) The following comments are general in nature in no specific order, as it would be inappropriate to suggest specific changes and then assess the final project. Comments will be added during this week and you still have one week before final submission.

* There is no concise list of changes made to your project on the basis of peer assessments.
* Timeline of Embryo Development early stages, are in the introductory text said to be in hours, but it would be good to see it in the list as well.
* [[:File:Sizes.JPG]] Relative sizes, but no absolute size or scale given.
* A general comment about images. When you click an image and it opens, the information below the image should have an explanation of what the image shows, a reference (if from a paper) and a link to the original source (if available) as well as copyright information.
* Did you actually read the terms of use for this image that you cut n pated into the image description? [[:File:Rabbit_hybrid.jpg]] "For this purpose alone you may retrieve and display the Content on a computer screen. You may also print out, but not photocopy, one copy of individual files on paper and store files in electronic form on disc, but not on any server or any other storage device connected to a network where the Content could be accessed by other users." It clearly states that you cannot use this image online.
* Chromosomes section, images have no legends and structure not clearly organised.
* There needs to be better checking of your spelling and grammar, for example [[:File:Rabbitmalformation3.jpg]] "Plant Patkology of Tke Rockefeller Institute for Medical Researck", these mistakes while not major, suggests a lack of reviewing of your work by the group.
* Just a comment on project "feel", when several people work together on a project and insert their parts, the final project sometimes has an uneven style. Now that you have time to tidy up, try and get a common appearance throughout your project.

==Constructive Criticism of Peers==

--[[User:Z3218657|Sally Clarke]] 09:32, 1 October 2009 (EST)
Nice work Guys!
- Fantastic images used throughout - maybe a few more in the timeline so we can understand what is going on
- As you start going down the page though the information starts to read a bit haphazardly, for example the developing body; jumping for section to section and the timeline section. it would be great if you could clean this up as it doesn't really flow.
- The section on the abnormal development is great.
- The page is quite long - Maybe you could condense some of the text as it is kind of slab like
- i really enjoyed the breeding section
- The advantages and Disadvantages would be better in a table.

--[[User:Z3223194|Bronwyn Lewis-Jones]] 08:08, 1 October 2009 (EST) Hi Group 1! This is obviously a well organised and well researched assignment. I found it very informative. There are (of course) some things I feel could improve the overall submission. I loved that the timeline/staging section was clear and concise, however I think it could be improved by adding more colour/pictures to maintain the readers' interest. There is also a lot of content which might be alleviated by reducing the section on abnormal development. Hope this helps :)

--[[User:Z3218146|Julianna Lam]] 01:11, 1 October 2009 (EST) good job guys.
-Theres alot of relevant information.
-The timeline and staging bits are very well written and clear but i think you should add a few images in there to match up with the text.
-The image for the genetics bit is awesome.
-The page is nicely set out.
-Too much information about the abnormalities.

--[[User:Z3258567|Sando Rashed]] 20:04, 30 September 2009 (EST)hey guys, your page looks good, starts off well as there is not a bunch of information just thrown in, the information used is well thought, with the history you might want to put the advantages and disadvantages into a table to make the page look a bit more tidy and easier to read when we go through it (you can also do this with the info under genome), the group makes good usage of diagrams but towards the end diagrams die out, you might want to make the current research part of your assignment into diagrams and steps as there is just a bunch of information thrown there and alot of reading needed, if you put it into steps or diagrams it will make the marking process and reading process easier and allow us as reader to understand the information with ease, other than that the page looks quite good, well done on all your contributions

--[[User:Z3218792|Gabriela Pinget]] 21:51, 29 September 2009 (EST)

Nice page. I particularly liked the idea of lists of what is to come before each flood of information as was done with the ‘history of model use’ section.

- Nice easing into the topic with ‘advantages’ and ‘disadvantages’ lists.

- I liked the of rabbit embryo development to that of humans- puts it into perspective

- Good glossary- informative but not over- the- top

- Nice genetics section! Easy to read and a great use of illustrations to break up the information

- I also like that you took a page out of Mark’s book in the addition of the abnormalities section

Improvements:

- Perhaps some pictures of embryos throughout development.

- It’s a little confusing that the development jumps back and forth according to the body part developing. Maybe it should be categorised according to time of development instead for greater clarity at first glance

--[[User:Z3295026|Joe Nassif]] 17:01, 29 September 2009 (EST)

Your assessment has come along great in regard to the criteria format. There are a few alterations that could improve your project, the following alterations may enhance your wiki page:

'''-''' The usage of rabbits for experimental models in both science and medicine could be state under the history section to allow background information for the readers to become aware of the topic and why the rabbit have been used to study specfic medical procedures and diseases.

'''-''' Secondly the information on 'Transgenic Rabbit' should be shifted toward the genetic information on the rabbit. So far the project is looking and coming along great except for minor edits.

'''-''' Background information should be placed subsequent to the introduction allowing the reader to understand why this specific animal is used for specfic purposes.

'''-''' Figures/Graphs and the illustration of the anatomy and genetic development of the embryo were useful and clear allowing the viwers to understand and learn through the demonstration of pictures which were extremely informative.

'''-''' Genetics: the Genetics and Abnormalities information was great and very informative. It was great how the group compared the embryo with the human chromosome allowing the audience to understand the difference between both.

'''-''' Abnormalities: Information and details which were in the genetic section provided informative and interesting information, and it could be truncated a bit, additionally just discussing the chromosome development of the rabbit.

'''-''' Current Embryology Research: information in regard to stem cells should be brief and truncated. Example in regard to stem cell research should have brief and simple model explaining the process and why it used.

'''-''' Consequently, I thought the project was good it flowed and was very informative. The information was detailed, and the illustrations were useful and allowed the readers to gain a brief overview on the topic and it usage in history and in current research. Overall group 1 seem to achieve the critriea outcomes and summarised the topic really well, the comparsion to human embryo development througout the text was great and is a good referencing point in comparsion to the species choosen.
Great job --[[User:Z3295026|Joe Nassif]] 17:01, 29 September 2009 (EST)

--[[User:Z3255007|Sadaf Masood]] 12:09, 30 September 2009 (EST)Hello Group 1! Congrats on your awesome group project! I must say im very impressed with all the information you have posted and i have listed down the good bits and the bits that need to be improved. Since i am posting this a lil late, i have seen that u have already improved your project and few aspects...Good Job guys!

1. Very brief introduction...maybe just a little bit more info will be perfect

2. Abnormalities section is very informative and well researched, but very long, how about making it a little more precise?

3. The Advantages and Disadvantages of the using Rabbit is just simply perfect

4. The timeline is just a little confusing, as its divided into development of different parts, which breaks the time flow.

5. Pictures for every stage would make it more visually attractive rather than just reading text

6. Great Glossary!

There were few things earlier that need to be improved but you guys fixed it as soon as comments were posted so basically you guys rock :)An excellent effort guys. Best Wishes

# --[[User:Z3217015|Mitchell Mathieson]] 09:45, 25 September 2009 (EST)Very nice. The information was maybe a bit spread out, with heaps of gaps everywhere (formatting???), but the information was there, and relevant, and easy to read. I like how there was tonnes of information on current research, as I think that was the main aim, but the abnormalities went a bit over board, and didn't need that much attention I think. pictures for stages would have been nice, unless there were none???? The references are top notch, and the glossary is pretty amazing, and in the right place. Overall very good, I think formatting was the major downfall though, as it makes the page that much longer, and hence a little bit more difficult to read.

--[[User:Z3224449|Elide Newton]] 14:12, 26 September 2009 (EST)
HEllO GROUP 1: Well done on such a great assignemnt, looks like you have all worked very hard. Well my one point of constructive criticism would be to reduce the writing content. for example. In the current research section, you have two scientific process of transgenic rabbits as well as cloning which is described in how these are done. why not draw a step by step diagram, and put these written steps in the link to the image. that way it is more visual, the info is still there under the image link, and the page wont look as daunting to read. :) hope this helps!

--[[User:Z3254857|Begum Sonmez]] 00:46, 26 September 2009 (EST)
Hello Group 1. Firstly, I would like to let you all know that you have all done a great job. I'm impressed. I have a few suggestions that I think mite help to improve the page even more:

*Introduction:

1)For the first sentence (the characteristics that make the rabbit an excellent model for study), mention the section 'Why are we using rabbits?' under History section.

2)For the second sentence (study that developed and improved micromanipulation techniques), mention the 'Transgenic Rabbit' section below under the genetics section. I've read the entire project page, and the introduction was the only place I found that was not precise enough (which is a great thing). These are minor things, but I think they will help with improving your project page.

3)Breeding information was informative.

4) A suggestion: Place the history section after the Introduction. This gives the viewer an overview of the use of the rabbit embryo. This way the viewer is first subjected to a few examples of the rabbit embryos use. It also allows him/her to understand where the rabbit embryo sits in with history. I guess this is a matter of personal preference.

*Timeline:

1)Graphs, and the illustration of the zona pellucida and mucin coat were very clear and informative.

*Staging: I had no problems with it. The lack of information I think was a plus. It touched on the content in the Timeline section.

*History:

1) I loved the idea of the 'Disadvantages' of the rabbit embryo, it seemed unbiased. The brief timeline provided a clear and short summary.

2) Spelling mistake under 'Discovery of Graafian Follicle', 2nd paragraph. I think it's previous instead of 'previcous'. Also, the 2nd paragraph under this heading does not flow that well. Try rephrasing the 2nd sentence.

*Genetics:

The Genetics and Abnormalities section flow into eachother very well. I appreciated the comparison of the rabbit chromosome to the human chromosome.

*Abnormalities:

1) The information provided under Hydrocephalus and Brachydactylia was informative and interesting, but it contained too much text. I suggest you narrow it down and make use of Dots point, numbering, bold/italic words, and/or sub-sub-headings.

*Current Embryology Research:
1) There is too much information under stem cells. There is 2 examples of studies dealing with stem cells. A suggestion would be to just have one, and have a link saying 'Koga's research on Stem Cells'.

2) Have the section 'links to Research labs and researchers' placed at the end of current research. That way, the information on the page will flow smoother.

Overall, I thought there was a consistent structure in each section. The information was informative, and the pictures were relevant and helped me better understand the topics of discussion.

--[[User:Z3252340|Emily Wong]] 10:58, 27 September 2009 (EST) Firstly, great work. It is a well researched, structured and organised page. The content is very in depth and includes information on all of the specified areas. It is well referenced, with an extensive reference list indicating the amount of research put into the page. Some areas are more detailed than others. For example, the staging section is quite short and concise where as the Abnormal development section is extremely long considering it is not a needed topic. There is moderate use of pictures and diagrams, but more use could benefit the page as it may be able to negate some of the large slabs of text. The comparisons made between the human and the rabbit embryos are a good part of the project page. Each member of the group has contributed to the page and provided a lot of information on the section of content they were working on. What would improve this project is a more even distribution of information, particularly more detail in the stages, a few more diagrams or pictures to negate some of the text presented, more of a focus on current research i.e. what each method is being used for and less on the process behind each method.

--[[User:Z3126345|Gang Liu]] 14:26, 27 September 2009 (EST)In my opionion, this is a well constructed page. It includes major subheadings such as history, timeline, stages, genetics and current research. It is very concise and straightforward, which makes it easy to read. For example, a short introduction paragraph,"...the rabbit is an appropriate animal model as the results from many experiments are significant to that of other mammals, including humans.", explains to reader why rabbit is such a suitable model.

It also provides a logic flow. For example, in history of rabbit model use section, it has provided advangtages and disadvantages of model use. This is appropriate, as it demonstrates the significance of rabbit model use in scitific discovery. In addition, it has provided detailed background information for each discovery. This makes it interesting to read.

It is also important to compare development of embryo between rabbit and human. For example, "... the similarities of this developmental pattern in humans and rabbits, suggests that the same growth increment is required to achieve the same stage. The main difference observed between human rabbit gestational duration is due to the fetal growth phase...", this has suggested human and rabbit share many similarities. Not only this page has demonstrated detailed written information of timeline development, it also provided graphics to reinforce the concept. For example, the hand drawing of developing embryo. As well as the comparison between human embryo and rabbit embryo timeline development.

It is also interesting to learn that rabbits have 22 pairs of chromosome, whereas humans have 23 pairs of chromosome.

Sections such as abnormal development and current research have demonstrated extended research and understanding. For example, hydrocephalus, spina Bifida, stem cell research and cloning techniques. All of these have showed the in depth research in textbooks, journals and internet based literatures.

However, this page can be improved by considering the following points.

*Provide pictures for individual stages. Get visual, and make the stages interesting to read.

*Reformating in sections such as hitory and genetics. Make pictures appear on the same side of page.

*Typo: "A rabbits potential for reproduction..."

*Sections such as abnormal development and current research are too lengthy. Might consider shrink the content.

*Lack of glossary.

Overall, big thumbs up!

--[[User:Z3252231|Angama Yaquobi]] 01:12, 28 September 2009 (EST)
First of all i would like to congratulate all the team members for a great team work.
Well done guys!! The group project looks amazing, the information presented is very concise
and straight to the point which makes it very easy for the readers to grab
the important information that they need to enhance their knowledge.
I like the section of history, the information is very clear,
and i like the idea of providing some background knowledge to the readers
about the disadvantages of the use of rabbit.
The history section can be improved if the infomation is expanded
to give some more detailed background knowledge althought
i like the idea that the information is concise describing each
scientists contribution towards the model.
The section for timeline is impressive, in my perspective its a great idea to cover alot of content in a very smart way
which is by the use of subheadings to make it easy to understand for audience.
Staging section is also very well presented but the information presented
in a table would even look better if there is use of some pictures
to make it more interesting for its audience. Genetics section
is beautifully presented, all the information is there with some
amazing pictures but will look much better if there is some work to
be done for the structure of it especially the paragraph under the
heading of 'abnormalities'. Section for "Abnormal Development" gives
the readers useful amount of information but i think its very lenghty,
use of dot points can make it look even better and easy to understand.
The same for Current embryology research, great amount of information but
in my perspective replacing the paragraphs with some dot points with
heading and subheadings would further enrich understanding of readers.
Also glossary would complement the webpage. But overall,
great amount of information which shows alot of research
which has been done by all the team members. Well done guys!!

--[[User:Z3217686|Thomas Dangerfield]] 13:29, 28 September 2009 (EST) Hey guys! Good work on your assignment! Plenty of info which is good, and very well referenced. The glossary is a good idea too! I do agree with a few others about the lots of clear spaces in the formatting, and the lack of pics in the timeline though. Also under the genetics section, maybe aligning the pics on either the left or right side instead of both left and right, and possibly putting them as thumbnails could also work. In the abnormalities section, there might have been a little too much info that probably wasn't needed, but i do like the effort put in. Over all, possibly more time spent on formatting and determining which sections are more important and which sections may need to be limited. Other than those points, the whole assignment seemed very well done!

--[[User:Z3215682|Carly Mooney]] 11:32, 29 September 2009 (EST)
You assignment is visually appealing and the genetic information e.g. the number of chromosomes of a rabbit was very interesting.There are some additional sections you have added which really complement your assignment e.g the abnormalities and I really liked the advantages and disadvantages of using the rabbit model. The few suggestions I would make is to:
* include pictures in the stages section
*place the pictures throughout the text (e.g. to left or right). You did this up until abnormalities and I felt it broke the flow of the written text.
* and maybe move the links to current research labs up closer to the current research section, just to keep it all together.
Overall very impressive though.

--[[User:Z3220040|Joanne Raffel]] 15:25, 29 September 2009 (EST) Nice wikipage, the page looked interesting however I agree with some others that the formatting of the page was inconsistent. I thought the referencing was great but found it a bit confusing with the reference numbers after the paragraphs. I thought the subheadings werent distinct enough, especially in relation to the text, which made it difficult to read. The history section could be formatted to make the information stand out and a lot more appealing, I would recommend including pictures if possible that link to the text and making the advantages and disadvantages into a table rather than listing it. I especially liked the comparison between the rabbit and the human embryo, however some of the information for the timeline section was too heavy for the page, I would recommend only using some of the information on your actual page and having the rest as links to separate pages. The staging section was very bland and would be more appealing with pictures. I dont think its necessary to cite your entire reference within the text, especially in the genetics section, maybe instead of writing the entire reference, you could just state The Broad Institute or just the people related to it. The abnormalities section was a good inclusion however it was very extensive, along with the current research section. Overall a very good wikipage.

----
*Hey, Well done guys!!! I think our group worked pretty well! I think we communicated each other well and did very best for their section. I fixed my spelling mistake and problem with sentence! As Begum mentioned, I think placing the history part after the introduction is better idea. --[[User:Z3126328|Jin Lee]] 13:36, 26 September 2009 (EST)

*Hey guys,
the project has come together brilliantly! it looks quite good. Hopefully mark will like it! ill add some terms to the glossary and try do some formatting (the first image is a little too big i think!) --[[User:Z3186093|Jenny Guy]] 10:28, 24 September 2009 (EST)

Hey. Yep all good. I had to get rid of the pics, so stages table is now blank. Im pretty much done. I'll see what i can add to the glossary. thanks :)--[[User:Z3185685|Sumaiya Rahman]] 23:34, 23 September 2009 (EST)

Hey all, I'm going to start a glossary and add it under the reference section. Scan your text and add to the glossary in alphabetical order. Also under the marking criteria, it says to provide links to researchers and research laboratories.....i'll start that under the glossary. Everyone else OK with their stuff?--[[User:Z3187802|Vishnnu Shanmugam]] 23:08, 23 September 2009 (EST)

Hey Sum, The images look fine but I don't think you can use the images like that since the journal KARGER is being particular about its copyright laws. I tried tracing around the images but it does not seem to resemble anything like an embryo. I did however find this link...go to it and scroll down to the images of the developing embryo. You might be able to edit it to resemble rabbit embryo. --[[User:Z3187802|Vishnnu Shanmugam]] 15:10, 23 September 2009 (EST). To get to the link, Google image search "rabbit gestation"....click on the "rabbit,gestation age" image from nature.com
Also google image search "The Haeckel embryo sequence"...could be useful after some editing

oh my god!! I summarised all of my research and wrote down on the page. Then I blew up everything!!!
it says 'edit conflict' what da?? I lost all of my work...it was my stupid mistake...--[[User:Z3126328|Jin Lee]] 01:06, 23 September 2009 (EST)

Oh also.. let me know if the images look stupid --[[User:Z3185685|Sumaiya Rahman]] 00:34, 23 September 2009 (EST)

Hey thanks vishnuu. I put some images up in the stages table. I did edit the pictures, but im not sure if im allowed to use it like this? have a look and let me know. Also im not sure what is going on with the reference section seems kinda all over the place, so i havnt added mine in yet. Maybe we should fix that up somehow? :) oh LOL about the breeding rabbits bit! haha
--[[User:Z3185685|Sumaiya Rahman]] 00:31, 23 September 2009 (EST)

Hey Sum, Sorry for the late reply. For $330, I'd rather breed rabbits and take the photos myself. I had a look at the original images, what we can do is trace around the developing rabbit embryo using the pencil tool on an image editing software(eg. microsoft paint - already preloaded into most windows). Then upload the image to the assignment. Does your PC have adobe fireworks?...extremely good for tracing images. If not, have a go at it with microsoft paint....I shall also have a go at it, then I shall let you know on this discussion page at about 3PM t'morrow. If any good then I'll send it to your student email. If not, we discuss potential alternatives. good luck Sum! --[[User:Z3187802|Vishnnu Shanmugam]] 23:51, 22 September 2009 (EST)

Yep thats the article i used for the developmental stages and put in a table. I should have my timeline posted by end of today. I also couldn't get permission to use the pictures as they wanted about $330 for me to use it!! no thanks. I'll see if i can work it in somehow. Vishnuu did u have any ideas on editing the images?? --[[User:Z3185685|Sumaiya Rahman]] 12:29, 22 September 2009 (EST)

Have a look at this article, it's helpful for comparison bt rabbit and human in developmental stages!--[[User:Z3126328|Jin Lee]] 13:35, 21 September 2009 (EST)
*Sampled rabbit embryos were staged using the Carnegie criteria, in order first to determine if they were consistent with the rabbit developmental pattern, and second to compare this pattern with the human one. Our results show a suitable '''comparison of rabbits and humans in early developmental stages''', except for the neural growth.
[http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowAbstract&ArtikelNr=73136&Ausgabe=229537&ProduktNr=224239
]

Absolutely correct Juliana, my research articles and their links are labelled 1-6 so far, the rest is yours..... I'll fix it for you. A timeline image seems tricky and i'm unsure, send Dr. Hill an email on m.hill@unsw.edu.au and see what he says. We still have till thursday to finish everything, so don't be too worried....try to finish all your other stuff and leave the drawing of the timeline last.--[[User:Z3187802|Vishnnu Shanmugam]] 17:49, 20 September 2009 (EST)

*no.1-7 in reference section is mine. and I think links under Vishnnu's research on the discussion board is mine. let me know please. (I can't remember all of my researches)
I want to make a timeline image but I can't do it;;; I asked Mark few weeks ago but havn't replied yet....can somebody help me???--[[User:Z3126328|Jin Lee]] 17:26, 20 September 2009 (EST)

'''** Hey Jenny, dont worry!! the project is not due until next week! (24th) we will have it done by then!! I am still waiting for permission to use the pictures in my stages section, thats why it hasnt been done yet. Hopefully i can get permission, otherwise i'll have to draw them (or something) myself.''' --[[User:Z3185685|Sumaiya Rahman]] 14:03, 17 September 2009 (EST)

It says project due date 24th september.......if the due date had been brought forward why was it not posted on the project main page? --[[User:Z3187802|Vishnnu Shanmugam]] 13:48, 17 September 2009 (EST)

EVERYONE...WHY IS THE REST OF OUR PROJECT NOT DONE??
* vishnuu...its due TODAY!! how can you post things up next Monday? Please make sure youve referenced EVERY image and all text (i know youve said you need to do this...but its easiest done when writing the section as now you have to go back and find everything, insert numbers etc. Remember to put the reference in the reference section. For the current research section i thought this might help you (as during my lecture in another class they spoke about how rabbits are used in heart development. Is there anything that you've found to include this?). Also I found this website during my research so it may help you? [http://www.evergen.com/rabbit_experience.html/ Rabbit Experiments]
* sum - where is the timeline???? It doesn't exist? Where is it? Also, we need some sort of visual for the staging. Have you found an images? Could you draw the stages of embryo development? It just looks incredibly boring.
* julianna...you need to put up more other than just two historians...there is NO referencing whatsoever in your entire section. where have you found this information? have you put it in your own words or copied it? You need to add some more refences to the reference section at the bottom..there just aren't many to back up your research.

seriously guys. ive added photos and tried to spice up the project but i am NOT going to finish your sections for you. ITS DUE IN 3 HRS! i cant believe you guys haven't bothered to even try finish this. Im very disappointed and i think its slack to let the team down. --[[User:Z3186093|Jenny Guy]] 10:34, 17 September 2009 (EST)

----

Hey all, just need to finish editing the current research part before i post it up, also need to edit some of my images under abnormal development and also references. Should be all done by Monday. --[[User:Z3187802|Vishnnu Shanmugam]] 07:02, 17 September 2009 (EST)

--[[User:S8600021|Mark Hill]] 01:40, 8 September 2009 (EST) OK guys, this is still just a page of text......

--[[User:Z3126328|Jin Lee]] 14:50, 3 September 2009 (EST) I want to make a timeline?

--[[User:S8600021|Mark Hill]] 08:42, 21 August 2009 (EST) z3187802 has contacted me and has been away sick. He should still complete his components of the group project.

Our group is Sum, Vishnnu, Juliana and Jenny. Today in the lab we have decided to research the RABBIT! [http://embryology.med.unsw.edu.au/OtherEmb/Rabbit.htm/ Rabbit embryology from Mark Hill]

(Juliana's email belebele85@msn.com)

----
This is apparently what we need to include in our case study:
#Timeline of Embryo Development - how long (SUM)
#Staging - are there species specific staging, what occurs when (SUM)
#History of Model Use - when was it first used, (JULIANNA)
#Genetics - chromosome number, sequencing (JENNY)
#Abnormal Development (VISHNNU)
#Current Embryology Research - research papers and findings (VISHNNU)

Hey guys, maybe we should add a section comparing rabbit to human development
--[[User:Z3185685|Sumaiya Rahman]] 16:45, 6 August 2009 (EST)

That sounds like a good idea Sum....seeing that human development is the primary theme of the course, not including it would be criminal!. -vishnnu

Report:
* Links to resources and discussions are to be posted on the group talk page, the project page is for the actual assignment
* Final assignment will be marked by another group and everyone will be given a marking criteria
* No information should be obtained from Wikipedia and all information (tables & graphs included) must be referenced
* Please feel free to suggest any further topics which can be included

== Research: ==
So i think the main rabbit used in research is the oryctolagus cuniculus. Lets focus mostly on that (or at least i, Jenny, will since im going genetics). This link is great for the specific genetics: [http://www.ncbi.nlm.nih.gov/nuccore/AJ001588/ Oryctolagus cuniculus complete mitochondrial genome]

Here's some stuff about benefits of modeling from a textbook. I haven't yet written as my own so its still the authors material. Just thought it might benefit us all (and raise our morale as we thought the rabbit might suck..but it doesn't!) We're not "submitting" this as our own work so technically we're not yet copyrighting their material.
Ive cited the book here and the website i got it from:
[http://books.google.com.au/books?id=RY0rXE2HgqsC&pg=PA344&lpg=PA344&dq=rabbit+embryology+genetics&source=bl&ots=rbr3CuBRxY&sig=p8055w9oYQmsQeuN78mgXBGmRK4&hl=en&ei=NI2KStaQJIvSsQOEpMjEDQ&sa=X&oi=book_result&ct=result&resnum=3#v=onepage&q=&f=false/ Cibelli, J., Lanza, R., Campbell, K. and West, M. 2002. Principles of Cloning. Academic Press]

“Rabbits were one of the first species in which blastomere nuclear transfer succeeded; as a model species, rabbits placed a central role in developing the micromanipulation technologies in embryos.” Other advantages for using rabbits are:

# “The costs to animal procurement, animal care, and oocyte production in rabbits are relatively low compared to large animals.” e.g. a cow embryo is 30x more expensive that a rabbit embryo
# “The developmental biology of rabbit embryos and fetuses resembles more closely that of large farm animals than that of rodent model species, including the transition from maternal to embryonic control of embryo development.”
# “The pregnancy of rabbits is relatively short (1 month), allowing rapid evaluation of fetal and postnatal development. In comparison, the gestation length for cattle is 9x longer.”
# “The sizeable milk production of rabbits allows their use as test animals for therapeutic protein expression in milk, or as a living bioreactor.”
# “Rabbits are induced ovulators. Domesticated rabbits are nonseasonal breeders and produce multiple offspring in one litter. These reproductive patterns make the use of rabbits for reproductive research highly efficient.”

----
Here are some links i (sum) found which may help. Need to go through all the info and sort it out, But there are a couple of good diagrams.

'''Links for group assignment'''

http://www.reproduction-online.org/cgi/reprint/48/1/43

http://books.google.com/books?id=RY0rXE2HgqsC&pg=PA344&dq=rabbit+embryo+stages&as_brr=3#v=onepage&q=rabbit%20embryo%20stages&f=false - good for what studies in rabbit embryo have been used for. And has a good table for embryological stages!!

http://books.google.com/books?id=ljAKtC-iIrIC&pg=PA264&dq=rabbit+embryo+stages&as_brr=3#v=onepage&q=rabbit%20embryo%20stages&f=false

http://books.google.com/books?id=73bbKzqRvLsC&pg=PA156&dq=rabbit+embryo+stages&lr=&as_brr=3#v=onepage&q=rabbit%20embryo%20stages&f=false - picture of implantation

http://books.google.com/books?id=aZ7DQYFyxswC&pg=PA122&dq=%22rabbit+development+stages%22&lr=&as_brr=3#v=onepage&q=&f=false
-------
Hi I(Juliana) uploaded file, you guys can have a look.
Go to 'Upload File' tab and click ' early growth of rabbit trophoblast' file.

-------------
also I found an interesting article!
'''An Electron Microscope Study of the Embryology of the Intercalated Disc in the Heart of the Rabbit'''
Alan R. Muir
The Journal of Biophysical and Biochemical Cytology, Vol. 3, No. 2 (Mar. 25, 1957), pp. 193-202
Published by: The Rockefeller University Press

http://info.library.unsw.edu.au/cgi-bin/local/access/ej-access.cgi?url=http://links.jstor.org/sici?origin=sfx%3Asfx&sici=0095-9901(1957)3%3A2%3C193%3AAEMSOT%3E2.0.CO%3B2-S
--

[[User:Z3126328|Jin Lee]] 10:48, 25 August 2009 (EST)

----------------
I found helpful book in the library
'''Bensley's Practical Anatomy of the Rabbit 8thE by E.Horne Craigie, Toronto, University of Toronto Press 1948'''
--[[User:Z3126328|Jin Lee]] 13:27, 27 August 2009 (EST)

==Vishnnu's Research==

'''Background reading (Vishnnu)'''

Hey everyone. I'm starting my background reading section where I shall describe my research resources. They contain a summary and a link to the resource itself. I shall keep this "notes" section updated with each new entry I add.

'''Notes:'''

*Articles 1 & 2 - Juliana this could be useful to you.

*Article 2 - Sum this could be useful to you.

*Articles 3 & 4 - Abnormal development articles (added: 02/09/2009)

*Articles 5 & 6 - Abnormal development articles (added: 13/09/2009)

'''Article 1'''

'''The rabbit as a model for reproductive and developmental toxicity studies''' --[[User:Z3187802|Vishnnu Shanmugam]] 21:05, 30 August 2009 (EST)

''Robert H. Foote and Edward W. Carney'' ''Reproductive Toxicology 14 (2000) 477–493'' ''Department of Animal Science, Cornell University, 204 Morrison Hall, Ithaca, New York 14853-4801, USA Developmental and Reproductive Toxicology, ''The Dow Chemical Company Midland, Michigan 48674, USA''

'''Summary'''

This is a review article of a study looking at the use of rabbits in toxicological studies. The article describes the advantages in using the rabbit experimental model as opposed to the rodent model (mice & rats) and outlines the differences that make toxicological studies on rabbit embryos more accurate than rodents to resemble similar toxicological effects in human embryos. The article describes various techniques that can be used (eg. blood collection from marginal ear vein, artificial insemination, embryo collection) and solutions to some common problems that researchers face when using animal models. Very interesting article with a great quote from Robert Koch to open the eyes of researchers to other animal models:

“Gentlemen, never forget that mice are not human beings”

Want to find out more? Follow the link!

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6TC0-41SBGDH-1&_user=37161&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_acct=C000004218&_version=1&_urlVersion=0&_userid=37161&md5=4db60dc9352996fc4865b9d781b0128d

'''Article 2'''

'''Developmental stages in the rabbit embryo: guidelines to choose an appropriate experimental model''' --[[User:Z3187802|Vishnnu Shanmugam]] 21:05, 30 August 2009 (EST)

''S. Beaudoin; P. Barbet; F. Bargy''
''Fetal Diagnosis and Therapy; Nov/Dec 2003; 18, 6; Academic Research Library''
''pg. 422''

'''Summary'''

The article describes the various stages in the developing rabbit embryo and the rationale for using rabbits to study normal and abnormal embryology. The article details normal developments in the rabbit embryo and compares it to the developing human embryo. By making this comparison the article argues for the validity of rabbit embryology to better understand human embryology and also suggests that due to the similarities in the developing rabbit and human embryos, experiments on rabbit embryo’s yield more reliable results for human embryology. The article has some rare images on normally developing rabbits and breaks the developmental stages down (in days) describing the observable characteristics that form (eg. Limb development & body formation).
I have decided to use the image provided in the journal.

Definitely worth reading people, follow the link!

http://content.karger.com/produktedb/produkte.asp?typ=fulltext&file=FDT2003018006422

'''Article 3'''

'''Acheiropodia is caused by a genomic deletion in C7orf2, the human orthologue of the Lmbr1 gene''' --[[User:Z3187802|Vishnnu Shanmugam]] 04:32, 2 September 2009 (EST)

''P. Ianakiev, M. J. van Baren, M. J. Daly, S. P. A. Toledo, M. G. Cavalcanti, J. Correa Neto, E. Lemos Silveira, A. Freire-Maia, P. Heutink, M. W. Kilpatrick, P. Tsipouras''
''Am. J. Hum. Genet. 68:38–45, 2001''
''Department of Pediatrics, University of Connecticut Health Center, Farmington, CT;''
''Department of Clinical Genetics, Erasmus University, Rotterdam;''
''Whitehead Institute for Biomedical Research, Cambridge, MA;''
''LIM/25-D, University of Sao Paulo School of Medicine,''
''And Private Practice, Sao Paulo;''
''Private Practice, Porto Alegre, Brazil;''
''Department of Genetics, UNESP-Universidade Estadual Paulista, Botucatu SP, Brazil''

'''Summary'''

The article describes the developmental abnormality Acheiropodia can be passed down genetically from parent to offspring. Acheiropodia (also known as Horn Kolb Syndrome) is a condition where the distal extremities of the embryo fail to form. Although it is not fatal, the individual endures a very difficult life without hands and feet. The article notes that the disorder only affects the development of the limbs and has no other reported manifestations. The article defines this to be an autosomal recessive disorder which means that two copies of an abnormal gene must be present in the affected individual in order for the disease to develop. Thus, each parent passes an abnormal gene to the offspring. It is interesting to note the process of the malformation from genotype to phenotype: small deletions on the chromosomes produce abnormal genes, the abnormal genes are then passed down to the offspring, the offspring that inherits two of the abnormal genes is unable to code for the correct proteins and as a result, there is failure in normal development of limb extremities in the embryo phenotype. The article also has a shocking image of an individual with Acheiropodia which highlights the extent to which it can impact a person’s life and the urgent need to find a cure.

Read more about the exact nature of the abnormal gene using the link.

http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=1109034

'''Article 4'''

'''Epidemiology of congenital clefts of the lip and palate''' --[[User:Z3187802|Vishnnu Shanmugam]] 04:32, 2 September 2009 (EST)

''JOHN C. GREENE'' ''D.M.D. ,M.P.H.'' ''Public Health Rep. 1963 July; 78(7): 589–602''

'''Summary'''

This review article combines research to study the factors causing the developmental abnormalities cleft palate and cleft lip in populations. “Cleft palate (palatoschisis)” and “cleft lip (cheiloschisis)” are the terms used to describe the non- fusion of the upper lip, hard or soft palate and typically occur during the gestation phase of embryonic development. The article tables the occurrence of cleft palate and cleft lip in populations of people in various cities across the world. It also compares the occurrence of cleft palate and cleft lip in males and females. The article finds that the incidence of cleft palate and cleft lip is:

*Is random in males and females (ie. Occurs approximately evenly in both sexes)

*Is random in people living in different cities

*Is higher in children of mothers over the age of 35

*Is higher in white populations and lower in the negro populations which suggests possible role of environmental factors

*No concrete proof that cleft palate and cleft lip is hereditary

*Is higher in rats exposed to radiation and those fed riboflavin

*Is higher in rabbits and other lab animals exposed to higher stress through cortisone injections

Although the article is now quite ancient, it is interesting to note the incidence of cleft palate and cleft lip among people. It also shows the historical foundation of research into the causes of cleft palate and cleft lip through animal experimentation.

Read more about cleft palate epidemiology using the link.

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1915191

'''Article 5'''

'''Chromosome abnormalities in human embryos''' --[[User:Z3187802|Vishnnu Shanmugam]] 00:10, 13 September 2009 (EST)

''Santiago Munne & Jaques Cohen The Center for Reproductive Medicine and science of Saint Barnabas Medical Center, New Jersey, USA Human Reproductive Update 1998, Vol. 4, No. 6 pp. 842-855 European Society of Human Reproduction and Embryology''

'''Summary'''

As the title suggests, this article focuses on chromosomal abnormalities in the developing human embryo. To understand this article, it is necessary to first establish some basic definitions that are used throughout the article. Aneuploidy can be defined as the occurrence of one or more extra or missing chromosomes leading to an unbalanced chromosome number. Although most babies with an unbalanced amount of chromosomal material miscarry during the first trimester of pregnancy, those that are born have crippling conditions such as:

* Birth defects

* Turner's syndrome (disorder where a female child is born with only 1 X chromosome)

* Down's syndrome (disorder where child is born with 3 copies of chromosome 21)

* Edward's syndrome (disorder where child is born with 3 copies of chromosome 18)

* Patau's syndrome (disorder where child is born with 3 copies of chromosome 13)

* Klinefelter's syndrome (disorder where male child is born with 2 copies of the X chromosome and 1 Y chromosome)

Polyploidy is a type of aneuploidy where the baby has three, four, or more sets of chromosomes instead of the two present in diploids. Chromosomal mosaicism is when different cells within an individual, who has developed from a single fertilized egg, have a different chromosomal makeup. Most commonly there will be some cells with a typical number of chromosomes (46 chromosomes) and other cells with an altered number or structure of chromosomes.

The article explores the possible causes of chromosomal abnormalities resulting from pregnancy though techniques such as IVF (In-Vitro Fertilization) and ICSI (Intracytoplasmic Sperm Injection). It also analyses the role of FSH (follicle stimulation hormone), temperature, water and light in chromosomal abnormalities.

The article finds:

* High FSH concentration increases likelihood of chromosomal abnormalities

* ICSI & IVF techniques have increased likelihood of chromosomal abnormalities

* Chromosomes exhibit temperature sensitivity and changes in temperature can cause chromosomal abnormalities

Although the article makes a number of findings, it is yet to be backed up with convincing evidence; the article has some really cool images of the developing embryo soon after fertilization. Overall, an interesting read.

Interested? Follow the link!

http://humupd.oxfordjournals.org/cgi/reprint/4/6/842.pdf

'''Article 6'''

'''Evaluation of the Safety and Pharmacokinetics of the Multi-Targeted Receptor Tyrosine Kinase Inhibitor Sunitinib During Embryo–Fetal Development in Rats and Rabbits''' --[[User:Z3187802|Vishnnu Shanmugam]] 00:10, 13 September 2009 (EST)

''S. Patyna, J. Haznedar, D. Morris, K. Freshwater, G. Peng, J. Sukbuntherng, G. Chmielewski, and D. Matsumoto''
''Pfizer Global Research and Development, San Diego, California''
''Roche LLC, Palo Alto, California''
''Pfizer Global Research and Development, Kalamazoo, Michigan''
''Xenoport Inc., Santa Clara, California''
''Pfizer Global Research and Development,'' ''Groton, Connecticut '' ''Birth Defects Research (Part B) 86:204–213 (2009)''

'''Summary'''

The article looks at how toxicity affects embryo-fetal development. The article describes the abnormal changes that occur when Sunitinib (an oral inhibitor of multiple receptor tyrosine kinases) is administered to pregnant rabbits and rats. This experiment was performed in an attempt to mirror the effects of antiangiogenic agents used in cancer treatment. Sunitinib is an antiangiogenic agent and the use of antiangiogenic agents is not recommended for treating cancer in pregnant patients because of the potential harm to embryo-fetal development. Angiogenesis (the formation of blood vessels) plays a critical role in embryo–fetal development and antiangiogenic agents slow down and/or stop the formation of blood vessels in order to control cancer and stop its spread. In pregnant patients however, this has the potential to adversely affect the developing embryo and these adverse effects is what is investigated in this article.

The article finds the antiangiogenic agent Sunitinib at toxic levels can result in:

* Embryo death

* Fetal skeletal malformations including vertebrae malformation and cleft lip/palate

* Teratogenic effects in rabbits

* Decreased maternal and fetal body weight

This article is a recent study and provides important findings regarding the use of antiangiogenic agents, especially during pregnancy. Although the maternal effects are minimal, the adverse effects to the embryo are significant and permanent. The article makes good use of tables and graphs to juxtapose pieces of information and to show trends. It is very interesting to note the extent to which chemicals can impact the vulnerable developing embryo.

Read more at link. (Use institutional login from UNSW computers)

http://www3.interscience.wiley.com/journal/122262246/abstract?CRETRY=1&SRETRY=0

------
thank you so much Vishnuu~~^^ from Juliana
-----
I also changed the format if you guys dont mind--[[User:Z3126328|Jin Lee]] 18:33, 31 August 2009 (EST)
----

Hey '''Vishnuu''', that link you found with the stages is awesome! thanks so much. Do you know if i am allowed to use the embryo pics in that article on our wiki page?? i'm not sure about the copyright rules. It says at the bottom of the article "Reproduced with permission of the copyright owner. Further reproduction prohibited without permission."
Does this mean we can only provide a link to it on our page? if so that's a shame, because those pics were fantastic!! '''SUM'''

Oh i also added an introduction - sum

Hey Sum,
Unfortunately, since its copyright protected we can't use the image directly......but there is a way of getting around it....You can modify the image using picture editing tools, then simply reference where the original picture came from and state that it has been modified by you. Alternatively, you can trace around the picture and provide only an outline (this will be very difficult to do with detailed pictures, a good picture editing software is recommended). Either way according to whats written under '''editing basics''' we need to include a picture that has been drawn up ourselves in the project. Also, not sure if you are aware, but the project is NOT due on Thursday (3rd September), Dr. Hill has very generously given everyone an extension till after mid-session break. --[[User:Z3187802|Vishnnu Shanmugam]] 02:35, 2 September 2009 (EST)

==Julianna's Research==
[http://netvet.wustl.edu/species/rabbits/rabtmodl.txt]
HISTORY OF THE RABBIT (IN RESEARCH)

A. Discovered in Spain about 100 B.C.
B. Domesticated in the 1500's
C. Standardization of breeds in 1800's
1. Research Uses
a. 1852: Rabbits have DL-hyoscyamine
(a) Can survive belladonna
(b) Endogenous atropine esterase
b. 1884: Pasteur develops rabies vaccine
c. 1891: Heape performs embryo transfer
(a) Influence on phenotype of the
uterine environment
d. 1908: Ignatowsky produces atherosclerosis
(a) Fed diets of milk, meat, and
eggs
(b) Produced intimal lesions
(c) Believed lesions due to protein
e. 1928: Demonstrated intranuclear development
of herpes virus
f. Graafian follicle was first observed
g. Coat colors and Mendelian inheritance
h. Immunology studies
i. Testing of human use products
j. Basic science studies
k. Diagnostic requirements
l. Eye Research
m. Pyrogen testing
n. Fetal drug induced teratology
o. Parasite research

LITERATURE REVIEW OF RABBIT USE

A. 1956 to 1800 ... Over 8000 citations
B. 1966 to 1987 ... 130,000 citations linking the rabbit to
all areas of research
C. 1988 to present ... 821 citations under the search
criteria: Rabbit: Model: Human Disease
D. Numbers of Rabbits Used (APHIS; ILAR records 1989)

1967 504,500
1978 439,986
1982 547,312
1983 466,810
1984 529,101
1985 544,621
1986 521,773
1987 534,385

ADVANTAGES OF USING RABBITS
A. Provides repeatability of animal model studies
B. Large enough for single samples
C. Many stocks/strains as animal models
D. Easily managed
E. Quality of immunologic products
F. Ease of reproductive control

DISADVANTAGES OF USING RABBITS
A. Most colonies are a storehouse of diseases
B. Extremely variable to responses to general anesthetics

[http://www.ncbi.nlm.nih.gov/pubmed/18430597]
The rabbit as a model to study asthma and other lung diseases.Keir S, Page C.
Sackler Institute of Pulmonary Pharmacology, Division of Pharmaceutical Sciences, 5th Floor Hodgkin Building, King's College London, Guy's Campus, London SE1 9RT, UK.

No single animal model is able to reproduce all the features of human asthma. However, the similarities between neonatally immunised rabbits and human asthma highlight the value of this model in the investigation of asthma pathophysiology and in the development of therapeutic agents. Airway inflammation and airway responses to various stimuli including histamine, adenosine 5'monophosphte and antigen in allergic rabbits have shown similarities with the responses observed in asthmatics. Furthermore, functional studies in rabbit airways show they are poorly responsive to capsaicin as are human airways. Chronic pre-treatment with capsaicin desensitises the TRPV(1) receptor enabling studies into the effect of this drug in both rabbits and man. The allergic rabbit model has been used extensively in assessing the various classes of anti-asthma drugs and is sensitive to similar drugs as patients with asthma, including beta-adrenoceptor agonists, corticosteroids, phosphodiesterase inhibitors and theophylline. This article highlights the usefulness of the rabbit as a species to study lung biology.

[http://www.ncbi.nlm.nih.gov/pubmed/8447943]
Effects of strain and embryo transfer model (embryos from one versus two donor does/recipient) on results of cryopreservation in rabbit.Vicente JS, García-Ximénez F.
Departamento de Ciencia Animal, Universidad Politécnica de Valencia, Spain.

Differential effects of 2 transfer models for normal thawed embryos of 1 donor doe were studied on the offspring rate and their embryo survival at birth from 3 selected rabbit strains (SY and SB: synthetic strains, NZ: New Zealand White). Morulae were obtained 64-66 h post-coitum from 93 adult does treated with 25 IU of hCG (SY:36, NZ:27, SB:30). Morphologically normal morulae were frozen in the presence of 1.5M DMSO and stored in liquid nitrogen. Normal thawed embryos were transferred into the oviducts of synchronized recipient does of the same strain 48 h after being injected with 25 IU of hCG (SY:28, NZ:21, SB:24). Each recipient received embryos from 1 (single transfer) or 2 different donor does (double transfer). Significant differences were observed in the post-thawing percentage of normal embryos between strains (SY:95 +/- 1% and SB:85 +/- 3%, P < 0.05; NZ: ,91 +/- 2%). After transfer, no significant differences were observed in pregnancy rate and offspring rate between the transfer models, whereas significant differences were only found in survival rate when all transfers were analyzed (double: 24 +/- 4% vs single: 14 +/- 3%, P < 0.05). An effect of strain was detected in the pregnancy rate (NZ: 33% vs SB: 71%, P < 0.05; SY: 61%) and in the survival rate per donor doe on pregnant recipient doe (SY: 42 +/- 5 vs SB: 19 +/- 5, P < 0.05; NZ: 34 +/- 7%). These results suggest a differential embryo sensitivity with respect to their genetic origin in both the freezing-thawing and transfer procedures.

--[[User:Z3126328|Jin Lee]] 13:06, 3 September 2009 (EST)

[http://www.ncbi.nlm.nih.gov/pubmed/14064965?log$=activity]GROSS EFFECTS ON RABBIT EMBRYOS AND MEMBRANES OF X-IRRADIATION IN THE BLASTOCYST STAGE.

[http://www.ncbi.nlm.nih.gov/pubmed/11139224?ordinalpos=408&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum]Onset of zygotic transcription and maternal transcript legacy in the rabbit embryo.Brunet-Simon A, Henrion G, Renard JP, Duranthon V.
Laboratoire de Biologie du Développement, INRA, Jouy en Josas Cedex, France.

Onset of zygotic transcription is progressive from the one-cell stage onward in the rabbit embryo. Maternal transcripts remain fairly stable until the 8-16 cell stage when major transcriptional activation of the zygotic genome takes place. To understand the mechanisms of the maternal-to-zygotic transition in the genetic information governing development, we asked whether a progressive synthesis of zygotic transcripts takes over the maternal molecules, or whether the synthesis of zygotic transcripts is very abrupt and independent of the persistence of the maternal counterparts. To answer this question, we set up mRNA differential display experiments comparing the mRNA content of rabbit embryos at different stages during the preimplantation period. We isolated eight zygotic transcripts whose synthesis is abruptly turned on at the 8-16 cell stage. These transcripts are involved in general cellular metabolism and their maternal counterparts are still present up to the four-cell and even the 8-16 cell stage. This identification of early zygotic transcripts suggests that global long range modifications of chromatin structure result in a rapid increase in transcription rates during the major transcriptional activation of the zygotic genome.

[http://www.ncbi.nlm.nih.gov/pubmed/11245264?ordinalpos=409&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum]
Reconstruction of the heteroparental diploid condition in rabbit zygotes by nuclear transfer.Escribá MJ, García-Ximénez F.
Departamento de Ciencia Animal Universidad Politécnica de Valencia, Spain. mescriba@dca.upv.es

Studies on genomic imprinting showed that parental genomes have complementary roles during embryogenesis, are both essential and need to be synchronized in their embryonic stage for successful development to term. To our knowledge, these studies have not been performed in species other than mice. We studied the in vitro and in vivo development of reconstructed zygotes by combining female haploid nuclear donors and androgenetic hemizygous recipients. Haploid donor embryos at the 8- or 32-cell stage were obtained from electroactivated young rabbit ova (eight pulses maximum, consisting of 0 6 kVcm(-1) for 60 microsec each, 38 min apart) which were further cultured for 24 h or 32 h. Couplets formed by both the haploid male hemizygous recipients and haploid female donor cells were electrofused (2.2 kVcm(-1) for 60 microsec duration each, 30 min apart) and their nuclear configuration determined 122 of those fused (43%: 122/286) were diploid. Reconstructed diploid zygotes developed in vitro up to the compacted morula, blastocyst and hatched stages (1/8-nuclei x 50%, 18% and 9% vs. 1/32-nuclei: 47%, 25% and 19%; P > 0.05), respectively. In embryo transfer assays, both 1/32-reconstructed zygotes and control, non-manipulated zygotes were transferred to synchronized does Four live reconstructed fetuses (4/49: 8 1% survival rate) and five in regression stage (9/49: 18% implantation rate) were observed on Day 21 post-ovulation, whereas from control zygotes, 11 fetuses were alive (11/53 21% fetal survival rate) and 2 degenerated (13/53 x 24 5% implantation rate). Similar results were obtained from a final experiment, in which development was allowed to progress to term. Six live rabbit pups derived front experimentally reconstructed zygotes (11%; 6/54) and three fetuses in regression stage were obtained; values slightly lower than those derived from non-manipulated and transferred control zygotes (18% 9/50, live born rate).

[http://www.ncbi.nlm.nih.gov/pubmed/11589623?ordinalpos=412&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum]
Effects of leukaemia inhibitory factor on endometrial receptivity and its hormonal regulation in rabbits.Liu CQ, Yuan Y, Wang ZX.
Shanghai Institute of Planned Parenthood Research, Shanghai, P. R. China.

The effects of hormones on production of leukaemia inhibitory factor (LIF) and the uterine receptivity in rabbits were studied. In ovariectomised rabbits, LIF protein was not detected in control but upregulated by progesterone alone. Oestrogen had a slightly negative effect when the rabbits were treated with both oestrogen and progesterone. Mifepristone (Mi) inhibited the progesterone-stimulated production of LIF in rabbit uterus. The transfer of embryos to LIF-treated recipients significantly increased pregnancy rate (70%) and implantation rate (27%) as compared with control (pregnancy rate=40% and implantation rate=17%). The transfer of embryos to LIF and mifepristone-treated recipients significantly decreased pregnancy rate (30%) and implantation rate (9%). The results indicated that LIF protein had a beneficial effect on uterine receptivity and mifepristone prevented this effect. Copyright 2001 Academic Press.

[http://www.ncbi.nlm.nih.gov/pubmed/8447943]
Effects of strain and embryo transfer model (embryos from one versus two donor does/recipient) on results of cryopreservation in rabbit.Vicente JS, García-Ximénez F.
Departamento de Ciencia Animal, Universidad Politécnica de Valencia, Spain.

Differential effects of 2 transfer models for normal thawed embryos of 1 donor doe were studied on the offspring rate and their embryo survival at birth from 3 selected rabbit strains (SY and SB: synthetic strains, NZ: New Zealand White). Morulae were obtained 64-66 h post-coitum from 93 adult does treated with 25 IU of hCG (SY:36, NZ:27, SB:30). Morphologically normal morulae were frozen in the presence of 1.5M DMSO and stored in liquid nitrogen. Normal thawed embryos were transferred into the oviducts of synchronized recipient does of the same strain 48 h after being injected with 25 IU of hCG (SY:28, NZ:21, SB:24). Each recipient received embryos from 1 (single transfer) or 2 different donor does (double transfer). Significant differences were observed in the post-thawing percentage of normal embryos between strains (SY:95 +/- 1% and SB:85 +/- 3%, P < 0.05; NZ: ,91 +/- 2%). After transfer, no significant differences were observed in pregnancy rate and offspring rate between the transfer models, whereas significant differences were only found in survival rate when all transfers were analyzed (double: 24 +/- 4% vs single: 14 +/- 3%, P < 0.05). An effect of strain was detected in the pregnancy rate (NZ: 33% vs SB: 71%, P < 0.05; SY: 61%) and in the survival rate per donor doe on pregnant recipient doe (SY: 42 +/- 5 vs SB: 19 +/- 5, P < 0.05; NZ: 34 +/- 7%). These results suggest a differential embryo sensitivity with respect to their genetic origin in both the freezing-thawing and transfer procedures.

[http://www.ncbi.nlm.nih.gov/pubmed/14564113]
'''Developmental stages in the rabbit embryo: guidelines to choose an appropriate experimental model.'''Beaudoin S, Barbet P, Bargy F.
Department of Pediatric Surgery, Groupe Hospitalier Cochin-Saint-Vincent de Paul, Paris, France. sylvie.beaudoine@svp.ap-hop-paris.fr

Researchers involved in the field of congenital malformations are often forced to work on an animal model. Both accurate description of its normal development and comparative staging with human development will be mandatory. To complete the lacking medical literature, we herein provide such data for the rabbit model. Sampled rabbit embryos were staged using the Carnegie criteria, in order first to determine if they were consistent with the rabbit developmental pattern, and second to compare this pattern with the human one. Our results show a suitable comparison of rabbits and humans in early developmental stages, except for the neural growth. Copyright 2003 S. Karger AG, Basel

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== '''Lab 1 Questions''' ==

1)What is the protein that sperm binds to on the surface?
ZP3

2)Name the 3 stages of follicle development in the ovary.

- Primordial follicle
- Preantral follicle
- Antral follicle (Graafian)

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--[[User:Z3185685|Sumaiya Rahman]] 13:08, 6 August 2009 (EST)
== '''Lab 2 Questions''' ==

1. What factor do the synctiotrophoblast cells secrete to support the ongoing pregnancy?

Human Chorionic Gonadotropin (hCG)

2. What does the corpus luteum secrete to prevent continuation of the menstrual cycle?

Progesterone

3. What are the 2 main tissues to be derived from the germ cell layer continuous with the lining of the amniotic sac?

Nervous tissue and epithelium of the skin

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'''Links for group assignment'''

http://www.reproduction-online.org/cgi/reprint/48/1/43

http://books.google.com/books?id=RY0rXE2HgqsC&pg=PA344&dq=rabbit+embryo+stages&as_brr=3#v=onepage&q=rabbit%20embryo%20stages&f=false - good for what studies in rabbit embryo has been used for. And has a good table for embryological stages!!

http://books.google.com/books?id=ljAKtC-iIrIC&pg=PA264&dq=rabbit+embryo+stages&as_brr=3#v=onepage&q=rabbit%20embryo%20stages&f=false

http://books.google.com/books?id=73bbKzqRvLsC&pg=PA156&dq=rabbit+embryo+stages&lr=&as_brr=3#v=onepage&q=rabbit%20embryo%20stages&f=false - picture of implantation

http://books.google.com/books?id=aZ7DQYFyxswC&pg=PA122&dq=%22rabbit+development+stages%22&lr=&as_brr=3#v=onepage&q=&f=false

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--[[User:Z3185685|Sumaiya Rahman]] 13:14, 13 August 2009 (EST)
== '''Lab 3 Questions''' ==

1. What period of human development (in weeks) do the 23 Carnegie stages cover? 8 weeks

2. What part of the somite will contribute to the vertebral column? The ventromedial component - sclerotome

3. At what Carnegie stage does the human neural tube normally completely close? Stage 13

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--[[User:Z3185685|Sumaiya Rahman]] 13:57, 20 August 2009 (EST)
== '''Lab 4 Questions''' ==

1. Into what structure do most blood vessels empty before they enter the embryonic heart? The liver

2. What do the dorsal aortas become in the adult? The descending aorta

3. What are the layers of cells found in a tertiary villi?

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--[[User:Z3185685|Sumaiya Rahman]] 14:13, 27 August 2009 (EST)
== '''Lab 5 Questions''' ==

1. What was the question I said in the respiratory lecture would be part of this week's assessment?

Is it more common for a congenital diaphragmatic hernia to happen on one side or both?

2. What is the answer to the above question?

It is more common for a diaphragmatic hernia to occur on one side. Majority (80%) occur on the left side.

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--[[User:Z3185685|Sumaiya Rahman]] 13:59, 3 September 2009 (EST)

== '''Lab 6 Questions''' ==

1. Which is the more common clefting, cleft lip or cleft palate? Cleft lip is more common

2. What structures does pharyngeal pouch 1 form? tympanic membrane, tympanic cavity, mastoid antrum, auditory tube

3. Neural crest forms which cells within the skin? melanocytes

http://www.reproduction-online.org/cgi/reprint/125/4/479
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2694706

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--[[User:Z3185685|Sumaiya Rahman]] 13:46, 17 September 2009 (EST)

== '''Lab 7 Questions''' ==

1. Briefly; what is a myotube and how is it formed?
- Elongated mulitinucleated cells that have peripherally located myofibrils.
- They are formed by a fusion of myoblasts during skeletal development and eventually develop into mature muscle fibres.

2. What changes would I expect to see in the muscle fibre types in my legs if I:

a) Suffered a spinal cord injury
-Muscle atrophy
-conversion of slow twitch muscle fibres to fast twitch muscle fibres.

b) Took up marathon running
-Conversion of fast twitch muscle fibres to slow twitch muscle fibres
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--[[User:Z3185685|Sumaiya Rahman]] 13:32, 24 September 2009 (EST)
--[[User:Z3185685|Sumaiya Rahman]] 13:21, 1 October 2009 (EST)

Talk:2009 Group Project 5

2009-09-28T07:16:38Z

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==Constructive criticism==
--[[User:Z3217015|Mitchell Mathieson]] 09:32, 25 September 2009 (EST) I think the looks good. However, the information is very spread out all over the place, and there is a bit of irrelevant information, such as the anatomy of the frog. There also seems to be repeated information in the stages and timelines; such as having tables and text to say the same thing. There was a heavy emphasis on the stages of development (it pretty much takes up 3/4 of the page) which probably could have been done more succinctly. The formatting needs a bit of fine tuning (heading separated from their text, and gaps everywhere), but in general it is good; the information is quite useful and well written.

--[[User:Z3224449|Elide Newton]] 14:57, 26 September 2009 (EST)HELLO GROUP 5: Well done on your assignment. my one piece of advice on your assignment is all about improving the flow and purpose of your assignment. Firstly There needs to be a introduction to the frog. why the frog is used as a model for embryology? By understanding the stages of development and timeline of the frog we can study the frog as a model. Why it is a good model and our understanding can be linked to why is has been used in the past and why it is being used currently in the future. hopefully this introduction clarifies the purpose of your information, and gives an outline to what you will cover in the assignment. also there is lots of unimportant information in regards to this assignment which is clouding your purpose of timeline, stages, genetics, past, present and future research. with this introduction paragraph, stating what topics you will cover and how these fit into using the frog as a model for embryology, hopefully it will flow better. all the best!

--[[User:Z3126328|Jin Lee]] 16:32, 26 September 2009 (EST) congulatulation Group5. The assignment looks good however, if you can make some additions it will be even better. Here is my suggestions: firstly the reference needs to be looked after. secondly some of sections are irrelevant(I found the 'anatomy of the frog' is irrelevant) and too much general information about the frog. May be better to focus on the assignment cirteria. For the history section, information is lacking(it's too brief) may be trying to add some more details about the each scietists...eg. in 1976, please mention which doctor you are reffering to. For the current research section, some more information needs. Overall, the assignment is visually well represented but may be concentrate on the main sections like timeline, stages, genetics, history and current research.

--[[User:Z3187802|Vishnnu Shanmugam]] 21:37, 26 September 2009 (EST)Great work frog group. The assignment you have put together is informative and well organized. One of the best features of the project is how clicking on the image takes you to another page with detailed and thorough explanations of the image. It is also good to see that you have added extra sections such as “abnormalities of the frog” and “the egg”. I note that too many groups are only interested in the headings specified in the marking criteria and have not done any extra work. The glossary is also a nice touch. Ways of improving the assignment:

- The background section introducing the frog needs to have information on why the frog model is useful. Include information on spawning, maintenance of specimens, genetic attributes and genetic similarities with humans.

- Although the addition of extra sections is good, it needs to be relevant to embryology. The anatomy of the frog section concentrates on the anatomy of the adult frog which is irrelevant for this project.

- The assignment should contain links to research laboratories and researchers as specified by the marking criteria. The external links do not do this.

- Remove the signature and time stamping at different sections of the assignment. The group project is collective effort, and the final presentation should not look like it has been split up. Do not worry about your contributions as these are logged and available for viewing under the “my contributions link”

- Some links in the text transfer you to Wikipedia pages on the frog....these should not be used as a source of information in academic projects.

- The assignment needs to be properly referenced as there are no references made in the actual text. see www.lc.unsw.edu.au/onlib/ref_apa.html for help with APA referencing

Overall a good project, some changes and additions are necessary to make it outstanding.

--[[User:Z3252340|Emily Wong]] 11:06, 27 September 2009 (EST) Firstly, Great work group 5. This project is very informative, well structured but a little unorganized. There is an extremely large amount of text presented. Perhaps a few more pictures or diagrams to negate some of the written work would be a way to improve the project. The work is well referenced with an extensive reference list. There is a lot of information on content that is not required. A way to improve your project would be to summarise a lot of this unnecessary information and maybe try and place it under one of the content headings. It appeared that a lot of this information was about stages or time points so maybe you could include this information in one of those sections.

--[[User:Z3217686|Thomas Dangerfield]] 14:25, 28 September 2009 (EST)Hey guys! Nice job! Plenty of information present, it just seems to jumble around a lot. Definitely needs an introduction, and possibly the first available section could be moved to after the anatomy of the frog. I don't mind the basic anatomy of the frog by the way, as it provides a little background to what the reader is going to end up with at the end of the development stage. Also the images could have a caption about what is actually happening in the image or what the images are trying to describe. There also seems to be a whole of a lot of information and plenty of images on the development and growth of the frog, but comparatively little on the genetics section. Chromosome maps can be very handy and comparisons with the human genome can help establish a picture of what you are trying to say. Just some organization and possible sifting of information would do the assignment nicely! Still, a very nice job on the frog guys!

--[[User:Z3185685|Sumaiya Rahman]] 17:16, 28 September 2009 (EST) Hey guys! Wow congrats on the assignment. I actually like the extra topics on the page. It makes it interesting and gives a lot of background knowledge to the reader. As mentioned, i am not sure why you have put in your signature stamps, this is not necessary. A lot of good images have been used but maybe instead of using figure 1, figure 2 etc. under the images; you could write what the image actually shows. I think this is what we were told to do? The links to the images in each stage are really good and help convey the information. The other thing that would help improve your page would be the addition of a glossary. Well done overall!

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--[[User:S8600021|Mark Hill]] 01:50, 8 September 2009 (EST) Still coming along, you have a lot of interesting pieces of information and some fair images. But how do the images relate to the text and where is the linkage? It is always easier to paste a whole lot of text information without interpreting what it actually means. Some of the information is good, tough some text also looks to be sourced without referencing. Overall the page lacks an integrated feel and structure.

--[[User:S8600021|Mark Hill]] 08:45, 21 August 2009 (EST) This is a good start. It is important that the project page content/structure reflects what all members of the group have in mind. There should be a list of relevant references now on this discussion pages.

== Background Reading ==

--[[User:Z3255007|Sadaf Masood]] 21:44, 8 September 2009 (EST) This link is for you Gary
http://www.xenbase.org/xenbase/original/atlas/NF/NF1-10.html

--[[User:Z3126345|Gang Liu]] 15:18, 23 September 2009 (EST) hi could anyone tell me how to upload pictures on the main page. i'm trying to upload pictures from this link http://www.xenbase.org/xenbase/original/atlas/NF/NF1-10.html, into the last column of stages of frog embryo table. cheers!

Hey guys!!

I have only met one person in the group..and that was today in the lecture (3/08/09)

Still missing out on the third person here!

Lets decide on the animal guys before the lab!!!!

Cheers!

--[[User:Z3126345|Gang Liu]] 15:22, 16 August 2009 (EST)Hi all, I'm Gary and i've just enrolled into this subject mid-week last week. Will try to catch up with the group assignment and individual homework.

--[[User:Z3126345|Gang Liu]] 14:54, 19 August 2009 (EST)Hi group, since we are dividing the assessment. I would like to work on sections such as "The egg", "Fertilization", "Cleavage", "Gastrulation", and "Hand-drawing diagram". Thank you.

--[[User:Z3126345|Gang Liu]] 12:56, 20 August 2009 (EST)Hi all, Joe is working on the first six subheadings. And i'm happy to take whatever subheadings the rest of the group is not working on. Thank you.

--[[User:Z3126345|Gang Liu]] 14:07, 20 August 2009 (EST)Hi all, after this week's group dicussion in the lab, we split the tasks as the following:
*Joe is responsible for subheadings such as egg, fertilization, cleavage, gastrulation, differentiation and growth;
*Gary is responsible for subheadings such as anatomy of frog, timeline and stage(introduction), and abnormalities;
*Sando is responsible for subheadings such as reproduction(male and female)+random subheading;
*Sadaf is responsible for subheadings such as current research, genetics and glossary.

--[[User:Z3126345|Gang Liu]] 17:26, 23 August 2009 (EST)Hi all, should we mention ''Xenopus'', part of frog family? --[[User:Z3126345|Gang Liu]] 09:29, 27 August 2009 (EST)Please ignore this line

--[[User:Z3126345|Gang Liu]] 18:00, 26 August 2009 (EST)Joe, thank you for updating our group page. Will upload my contents as soon as possible.

Hey guys, i need the list of words for the glossary or do u want me to pick them out myself?
thanks!--[[User:Z3255007|Sadaf Masood]] 10:47, 27 August 2009 (EST)

--[[User:Z3126345|Gang Liu]] 11:24, 27 August 2009 (EST)Hi, sadaf, will upload my glossary by tomorrow. Thanks.

--[[User:Z3126345|Gang Liu]] 11:30, 27 August 2009 (EST)Hi group, i just realised there is no one doing history part. Is there anyone would like to take this part? Or else, i'll work on it. Let us know.

http://books.google.com.au/books?id=OeAf7ChZD8QC&printsec=frontcover&dq=frog+embryology&lr=#v=onepage&q=&f=false

sick website

http://www.youddl.com/

EGG:

http://www.youtube.com/watch?v=GO5YN_t1fqw
--[[User:Z3258567|Sando Rashed]] 18:17, 23 September 2009 (EST) as late as im posting this i havent had time this past week to upload my notes but im putting them up now

--[[User:Z3258567|Sando Rashed]] 18:18, 23 September 2009 (EST)Gastrulation of a frog embryology
An invagination of cells that is found in the area of the embryo where it occupies the middle of the gray crescent, this is the beginning of gastrulation.
This beginning is what creates the blastopore which in the future will become the anus, and a group of cells that would later on produce the notochord which will eventually become the backbone (also known as the speeman organizer). Stimulates the ectoderm to form neural tissue (rather than it forming skin), so it begins the staging of the neural folds, which eventually the tips of the folds will form the neural tube which will become the spinal chord and the brain.
During gastrulation three layers start forming, these layers are known as the ectoderm, endoderm and the mesoderm.
Layer Forms out of it

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Ectoderm which may form the Brain, skin, spinal chord

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Mesoderm which may form the Notochord, muscles, brain

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Endoderm which may form the Inner lining of lings, bladder, thymus forms here.

--[[User:Z3258567|Sando Rashed]] 22:24, 23 September 2009 (EST)Cleavage = the repeated division of a fertilised ovum
When the zygote nucleus forms the first cleavage forms, this nucleus undergoes a number of mitosis processes, a wrinkle forms down longitudinally passing the poles of the eggs where the sperm enters. This is how the egg is split up into two halves and this process is what forms the 2-cell stage.
The process of the second cleavage is the process that allows the 4-cell stage to occur, the wrinkle runs through the poles at right angles instead of running through it longitudinally.
The 8 stage cell is formed during the third cleavage it cuts across horizontally but it cuts through closer to the animal poles rather than the vegetal poles.
As cleavages continually occur a 16 and 32 cell embryo are formed, and as these cleavages continuously occur the cells closer to the animal poles divide more rapidly and in more numbers compared to the vegetal pole. Eventually with all these cells continuously forming the blastula forms and a blastoseal which is a fluid filled cavity forms within it (no growth of the embryo has formed).
--[[User:Z3258567|Sando Rashed]] 23:06, 23 September 2009 (EST)Anatomy of a Frog
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The anatomy of a frog has many specialized features that are unique to the frog to help them live in their environment, they have long sticky tongues that help with them to grab food, they have specialized bones in the legs to help them jump.
When under water frogs are able to breathe through their skin, the oxygen is able to diffuse straight into the blood through the pores on the skin; they also have lungs that allow them to breathe on land.
In frogs they have 3 valves instead of the 4 valves in humans, they have one ventricle and two atria’s, the spiral valve does not allow blood with oxygen to mix with blood that has no oxygen.
Frogs are able to listen to sounds that have a low pitch through their skin as well as hearing sounds with a high pitch through their ears.

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The Egg

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The egg of a frog is approximately 1.6 million times larger than a normal frog cell. While all the embryological development is occurring through time it will eventually become a tadpole.
The egg can be divided into three different regions, the top part of the egg is known as the animal pole, the bottom half of the egg is known as the vegetal pole and a segment between the animal and vegetal pole is known as the gray crescent.--[[User:Z3258567|Sando Rashed]] 10:09, 24 September 2009 (EST)

Fertilization
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This occurs once the sperm cell has inserted, following the insertion of the sperm cells meiosis II is completed, there is a 30 degree position change of the cytoplasm, gray crescent allows this change to be visible in some amphibians, the gray crescent is able what determines the expect ted outline of how the frog will form. The sperm cell joins with the nuclei of the egg which forms the diploid zygote nucleus. --[[User:Z3258567|Sando Rashed]] 10:09, 24 September 2009 (EST)

Talk:2009 Group Project 4

2009-09-28T06:56:46Z

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==peer reviewing==
--[[User:Z3217015|Mitchell Mathieson]] 09:39, 25 September 2009 (EST)Page looks good. I liked how there was heaps of information on the genetics and the current research (however, this was a bit too spread out maybe). There seems to be a lot of gaps in the text, so the formatting could be maybe tightened up. The references maybe should be formatted better, and there is repeated information (tables and text for stages), but I really like how clicking the image goes to another page with more information...that is cool. The drawings are cute as well. Overall very good, I think formatting was the downfall from that, but the information is top notch.

--[[User:Z3126328|Jin Lee]] 16:42, 26 September 2009 (EST) hellow group4~ very impressive assignment guys!well done! I really enjoyed reading your assignment. it was easy to read and the information was relevant. However, I found the formatting of the images and texts were too sqeezy. may be resize the images and line up with the relevant information. Also, I think the reference needs to be looked after as well. Overall, the contents of the assignment is very useful and interesting.

--[[User:Z3187802|Vishnnu Shanmugam]] 20:02, 26 September 2009 (EST)Congratulations mouse group on an excellent assignment. It is a real joy to read. One of the best features of the assignment is how it gets straight to the point with the use of sub headings “What did he do?” & “What did they find?”. Even the images used throughout the text are interesting, especially the fully labeled hand drawn images in the “staging” and “timeline” sections. Some ways to improve the assignment:

-There are some unnecessary graphs in the assignment such as “the average length of mouse embryo”, “number of cells” and “number of somites”. These could perhaps be combined into a single graph. It will also reduce the congested appearance of the assignment as it seems too densely packed with no particular focus.

- In current research section, it is advisable to reduce the number of research and focus on just a few but provide more comprehensive information on the background of the research, the findings and the relevance to human embryology. It currently contains too many different types of research that have described very briefly.

- Edit the "content" section at the top of the page as it's length seems to be getting out of control. It is perhaps better to exclude the sub headings “What did he do?” & “What did they find?” in the contents.

- The referencing in the text need to be completed as there are some sections well referenced and others with no referencing. see www.lc.unsw.edu.au/onlib/ref_apa.html for help with APA referencing

- A Glossary would also complement the text.

Overall a classy project, only some changes necessary

--[[User:Z3126345|Gang Liu]] 16:49, 27 September 2009 (EST)This is one of the better wikipage i have seen so far. It demonstrates not only extended literature research skill, but also an in-depth understanding of the topic. The content of this page has been consistent throughout. In addition, paragraphs are straigtforward and concise, and make the point. Detailed texts with accessory graphics are appropriate in here. In paticular, history section. It describes the model use in terms of details of experiment, and results of experiment. Stages and timeline are very self-explanatory and visually enhanced.

This project can be improved by considering the following points.

*Lack of glossary list. Need to provide meaning of words such as "polyestrous", "oocyte", "Ectoderm", "endoderm", etc;

*Reformat stages section. I found this section a bit "busy". Might considering resize the pictures.

Last few words. I have learnt from this page that mouse has the same size genome as the human genome; Mouse genes can be easily manipulated and studied; Mouse a high degree of homogeny with humans. Well done!

--[[User:Z3217686|Thomas Dangerfield]] 14:12, 28 September 2009 (EST)Hey guys! Wow so much info first off! Not entirely sure we need to know about everyone involved in the history, maybe could have collaborated and joined people together or possibly even left certain people out. To me, the whole page is like how mark described, with everything all one great smudge of info with no real formatting or sequence or continuation. It was just kind of like an overload and reading it was a little difficult at some stages. Also corresponding the images in the timeline could have been included in the text.

Also I think your numbering of figures is a little off in the timeline section, with figures 1-4 on the right and then you have figures 4-7 describing stages 12-14. Just seems that there is two figure 4's for two different images.

Love the large amount of research and information, but could just work on your presentation and you'll do fine! Great work guys!

--[[User:Z3185685|Sumaiya Rahman]] 16:56, 28 September 2009 (EST) Hey guys! Overall a very nice assignment with a great deal of information! You can tell you guys did a lot of research. The contents are massive! Maybe you could cut this down and not use so many subheadings such as “what did they do?”, “what did they find?” and only have a subheading for each researcher. The introduction is well written. The history of model use has some really good information. My only criticism in this section is that there are a lot of gaps and blank spaces. You just need to delete all the spaces. The staging section showed a lot of research and effort. Well done!! The only thing is, is it a bit too much? There are a lot of tables and images that it was hard to keep track. Maybe this could be set out differently and made to look less busy. The timeline of development is fantastic and set out really well. It is very easy to understand and the drawings are great! Once again the current research is very spread out with lots of spaces. Also adding a glossary may help the readers in understanding the text. GREAT JOB!

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--[[User:S8600021|Mark Hill]] 01:46, 8 September 2009 (EST) Well the content is there now, but what a mess, and I am not just talking about the formatting problem which can be easily fixed, you have no structure to your project, its not a matter of throwing everything at a wall and seeing what sticks. Work together for an integrated coverage. Timeline of development, is not the way to start your page with a huge table of data.

--[[User:S8600021|Mark Hill]] 08:43, 21 August 2009 (EST) OK guys, time to see some actual content uploaded on both your discussion and project pages.

* Timeline of Development - how long (Emily)
* Staging - are there species specific staging, what occurs when (Elide)
* History of Model Use - when was it first used, what embryology research (Begum)
* Genetics - chromosome number, sequencing (Angama)
* Current Embryology Research - research papers and findings (All)

Here is a link for timeline
[http://books.google.com.au/books?id=XLIarRWHikAC&pg=PT199&lpg=PT199&dq=mouse+embryo+development+timeline&source=bl&ots=fobLBRiacx&sig=cK4cuZah6Ksczs3o8v4NXQqoAyk&hl=en&ei=rGB6SvTHMMmIkAXB_piAAw&sa=X&oi=book_result&ct=result&resnum=3#v=onepage&q=&f=false
]

link for the mouse brain development timeline http://en.wikipedia.org/wiki/Mouse_brain_development_timeline

hey guys there is another interesting link about mouse development http://mouseatlas.caltech.edu/index_content.html

Hey Emily. The link below has a timeline that you can check out in your spare time. Begum.
[http://books.google.com.au/books?id=4juoa5xMs8oC&pg=PA31&lpg=PA31&dq=mouse+embryology&source=bl&ots=9tJAfRG4R6&sig=hjR5Zs-sL1sCW5FY8FnR5TMaUk0&hl=en&ei=LuuMSr_aCNjakAX714icDA&sa=X&oi=book_result&ct=result&resnum=9#v=onepage&q=mouse%20embryology&f=false]

Hi girls,
here is a link to a text book about mouse embryology it looks pretty good. hope it can help
[http://books.google.com.au/books?id=4juoa5xMs8oC&printsec=frontcover&dq=mouse+development&source=gbs_similarbooks_r&cad=2#v=onepage&q=mouse%20development&f=false]
let me know if the link doesnt work. Ive been working on the main page, so have a look and tell me what you think, Also what are we doing about references? If we have used information but put it in our own words do we need to put in text citations,or do we just reference the journal at the end? I just want to be very careful. Thanks!

Hey Elide, i think your work is looking really good. its very easy to read and understand. keep going!!!! emily

hey everyone,
I have uploaded some of my timeline work. I'm not sure if I've gone into to much detail or not and also on how is best to present the timeline. It is fairly basic and definately needs some work - especially on presentation, grammar, etc. let me know what you think.
Emily

good site for stages or timeline- atlas of pictures of stages- The Edinburgh Mouse Atlas Project [http://genex.hgu.mrc.ac.uk/]

Hello girls, it's Begum. I put some info under the history section. Wanted to let you all know that I've got a fair bit of info, and I will do my part as best as I can. Btw Emily, I think maybe dot from would be best for you, but if you can use those lines that I was talking to you about on Wednesday, that would be great...I know it's hard.

hey everyone, i have put some info under the genetics heading and some under research. I am still struggling to find the appropriate info related to the topic of genetics because there is alot of info abt the different types of stains used in labarotories but not the genetics. I emailed Dr.Hill and have asked him what to include in my section specifically,hopefully he will help. So far i have just started it needs alot of more work to be done,girls just read thru my section n leme know wt u think of it. have a nice weekend everyone. Angama.

Hi girls!
Begum, you history info is really good. If very interesting! I really like how you are doing it in order of dates of discovery and what they did, what they found etc! Cant wait to know more.
Angama, your doing well! it sounds like your finding the info hard to get. I'll keep an eye out for you! If your stuck on what you sound be doing then i might have a few ideas. I remember Mark Hill saying that you should compare the genome to the humans genome. so maybe if the genome is the same size as the humans, could you descibe similarities or differences? I know that there is a link to the mouse genome on the mouse web page he gave us ( next to the discussion link). Are you just ment to list the mouse genome sequence? could you go into what genes code what, eg which one codes for the sex linked gene, is it the X and Y gene etc? hopefully Mark gives you some ideas.
well as you might have noticed i've been adding to my stages. the only thing is im worried about there being too much info up there. basically ive tried to get all the info available included in my stages to make sure i cover everything, and then later i'll go over it all and edit and polish it up a bit. Ive done some drawings to the best of my ability, but i can scrap them if you all think they arnt professional enough. just thought i'd try to present the information differently. let me know if you think i'm including too much information. i think i'm having the same problem as you begum, there is lots of info! Elide

Thanks Elide. I'm trying. (Again, loved the artwork!)Btw, Emily, I had a think about your section and I think it might be too much 'clicking' back-and-forth if we link the displayed pic to the 'info' page. Don't stress, you've got the info (heaps which is excellent) but make sure you get some pictures soon so we can start drawing (I'm helping with the drawings as well ok). Mark said 'Nature' and 'Science' have useable images so lets make that our start.
BTW, I will be using the question mark symbol(???) so I don't forget to reference. Begum

Hey everyone, I have found an online text book. it has a chapter on genetics and history and a lot of other stuff. [http://books.google.com.au/books?id=Vt6nUmz1yEQC&pg=RA1-PA207&dq=mouse+development+anatomy&client=firefox-a#v=onepage&q=mouse%20development%20anatomy&f=false] Emily

Hey girls. If you've seen my section, the info is not on the main page, but linked to another page. I thought that it might make everything look more neat. I thought we could all do it like that. It's just an idea. Something different. Maybe we could have something on the main page (picture of a mouse). Your thoughts everybody? Begum

hey begum, ur work looks really good. i like the idea of linking the work to another page. - we don't have to worry about to much info being on the front page and it gives people to option of viewing the work if they want to. ive been working on drawings, i'll show them to you next week but am not sure how to upload them at the moment. Emily

Thanks! That sounds great that you like the idea. About the photos that you are drawing, if there by hand, you can scan them somehow. But overall,
1. click 'Upload File' on the left hand side of this page
2. New page comes up: click 'Browse' and choose your file that you want to upload.
3. Name it (under the Browse button)
NOTE: write down what you named the file as because like Elide says "...it's going to be lost in space!..."
4. Write down info/comments (like who is the author (YOU), and if the drawing is based on a picture)
5. UPLOAD!
6. Go to your section and just normally type this down to the area you want the picture to be seen:
[[image:THE NAME THAT YOU SAVED THE FILE UNDER.jpg|thumb|200px|right|WHAT YOU WANT THE FILE NAME TO VISUALLY COME UP AS]]

Your thoughts Angama and Elide? (about the linking of our sections to separate pages?) Begum.

Oh and another thing:
What do you girls think about my page, I've got a heading for each DATE and underneath each there are further subheadings (e.g. 'What did he do?'. Should I change them to just text, I mean, does it look messy with sub-sub-headings? Begum.

wow girls! great work.. okay so i asked mark about a new page and he said to avoid it because our info is meant to be on our one page. he said if there is extra information on what we wanted to say but is too much for the main page then have a link to our discussion page. (which is what im going to do) Begum your new page is fantastic!! you have done lots of work! but why dont you just put it on our main page? also girls i think we are getting too carried away with info. just keep it simple! i'm sorry i havent been around this week to work on it but i plan to get going asap. just fixing up some things, summarising, writing introductions etc.
did you all read his note about slabbing info onto our page?? how about some introductions, and sentences to ease ourselves into the content. planning on trying to work on that now anyway..

also lets get the information flowing. why dont we go intro, history of model use, stages, timeline, genetics, then current use.. what do you all think?

hey, i thing that that sounds like a good, logical way to do the page. i've finished the drawings, just need to upload them. About the timeline information, is there anything specific that i should include. the stuff that is on the page is a little vague and so i need some advice as to what are key points that i should include. i know that the drawing are very simplistic, let me know wjat you think about them. ive put one up below. i just need a way to link it to text. emily

Thanks Elide. You know, I think that's a great idea. Have it all on one page, seems less 'diverging...', seems more COMPLETE. I love the ORDER as well. I'll fix all that up!

Hey girls, please have a look at what i've done on the timeline. the images are all hand drawn based upon the text: 'the house mouse'. if anyone could give me any ideas on how best to present the pictures - which would be better - next to or below the text? keep in mind that it is incomplete and there is an illustration for each day of development (i.e. 19 in total). if you think that is too many let me know, some may be similar to Elide's ones. Also, do you think i should put some colour into the drawings? Emily

I love your work Emily. All you need to do is put the info on the growth of the mouse that is on the main page, onto the page with the graph of the growth of the mouse embryo...we talked about that before any way-AND I think your parts finished! Begum.
Angama, I added something to the end of your section that I thought was interesting. Have a look. And are you mentioning manipulation and 'shut-down' of the genes in your section?? Begum.
To everyone, apparently ''Mus Musculus'' is the scientific name of the common house mouse, not the mouse. I was thinking of editing that.

HEY EVERYONE! well i've added in some pictures just to make it look more visual, change them if you have better ones.. and i'm going to be working on the current research section tommorow. oh i also added some graphs like we thought of for emilys section.. so i think my section is finished finally! what do you think? can i just say, I think the whole thing looks great! you girls have been a pleasure to work with! :) Thanks so much!!

hi girls, i am sorry..i have been very busy during the mid-sem break and i know we all had our exams and assignments due. but i was having some issues in my family and also the exams and assignments so didnt really had the chance to read wat u girls have got on the main page. i just finished reading thru it and it looks amazing..WELL DONE GIRLS!! you all have done a marvellous job...Eldie and Begum thanks for suggesting some main points to add for the genetics.i am currently working on it.. hopefully tonight i will have all the information on the page..Begum i love how you have presented alot of info into a very easy and understandable way..it makes so much sense..n it looks very nice with the pictures. Eldie and Emily great amount of work and the pictures and the graphs are superb. i just had a look to other groups pages. n i think so far our page looks very interesting with concise info n amazing pictures. n Begum yes i read what you have added thanks for tht..i will cu girls around..gudluck everyone. cheers. Angama.

Girls can you please help me out.. i am so annoyed..
like rite now i was typing some info and when i clicked to save.
it says "conflict" so i think some one else is also editing
the page at the same time that i am. and i lost all my work..arghh..
so which means i have to type it all again.
is there any other way that it tells me that someone else
is also using it so i dont click on save or even preview
because when i do tht i lost all the work tht i had.
If anyone knows please let me know. thanks. Angama.

Current research : I have put some information in the current research part. not sure where they should be put. Begum, as discussed you can edit it or place it in its appropriate place.

Don't stress Angama at all, now you know, it will be over soon. Uploading it easy:

1. click 'Upload File' on the left hand side of this page

2. New page comes up: click 'Browse' and choose your file that you want to upload.

3. Name it (under the Browse button) NOTE: write down what you named the file as because like Elide says "...it's going to be lost in space!..."

4. Write down info/comments (like who is the author (YOU), and if the drawing is based on a picture)

5. UPLOAD! 6. Go to your section and just normally type this down to the area you want the picture to be seen:

It's easier than it is typed! Of you still have problems I will be at the embryo lab, of there is exams there the ANAT LAB opposite to it, if not Level 3 library computers.

[http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=19538749| maternal diabetes alters transcriptional programs in the developing embryo], [http://www.ncbi.nlm.nih.gov/pubmed/19414407?ordinalpos=35&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum|Abnormal mammary gland development in MMTV-CBLC transgenic mouse], [http://www.ncbi.nlm.nih.gov/pubmed/19394325?ordinalpos=40&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum|Sonic hedgehog signalling inhibits palatogenesis and arrests tooth development in a mouse model of the nevoid basal cell carcinoma syndrome.], [http://www.ncbi.nlm.nih.gov/pubmed/19358209?ordinalpos=55&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum| Fibroblast growth factor 18 gives growth and directional cues to airway cartilage.]

Hi girls, i think i have completed my section. could you all please just read thru it and leme know wat you think of it. i did it to the best of my ability. Hopefully you will all like it if you girls think therez anything more to add or to delete leme know..thanks. gudluck girls. Angama.

Angama your work is fantastic! Thanks so much! im sorry i wasnt around to help you with the problems. hope it went okay. your info is perfect! im very happy with our page! lets hope everyone else is :)

I love it Angama, good work! And the pictures you uploaded are very interesting. Cool. Awesome. Your done!! Begum.

Thanks Begum :) Girls gudluck and cu all tomorrow. Angama.

== Staging of mouse embryo development ==

===Theiler stage 6-11===

{| border='1px'
|+ Table 2: Mouse embryonic staging from blastocyst implantation to pre-somite formation (Theiler stages 6 to 11)
! Theiler Stage !! Embryonic age in Days Post Coitum (dpc) !! Stage Characteristic !! Cell characteristics !!
|-
|6
|4.5 (range 4-5.5)
Human carnegie stage: 4
|Attachment of blastocyst
-Implantation
|Embryonic Endoderm present covering the blastocoelic cells of the inner cell mass.
|-
|7
|5 (range 4.5-6)
Human carnegie stage: 5
|Implantation
-Egg cylinder formation

-Ectoplacental cone
|Inner cell mass increases in size
-Epiblast formation (enlarged mass)

-Proximal cells are cuboidal in shape

-Mural trophectoderm is lined by primary endoderm
|-
|8
|6 (range 5-6.5)
Human carnegie stage: 5
|Differentiation of egg cylinder into embryonic and extra-embryonic regions
-Pro-amniotic cavity formation
|Trophoblast giant cells invade maternal tissue
-Maternal blood invades the ectoplacental cone

-Reichert's membrane appears

-Implantation site is 2x3mm
|-
|9 a)
|Pre-streak
|Advanced Endometrial and egg cylinder stage
-First evidence of embryonic axis
|Morphological difference can be seen between embryonic and extra-embryonic ectoderm
-Maternal blood further invades ectoplacental cone

-Uterine crypts lose their original lumen
|-
|9 b)
|Early streak
|Gastrulation begins (later in stage)
|First mesodermal cells produced
|-
|10 a)
|7 (range 6.5-7.5)
Mid streak to late streak
Human carnegie stage: 8
|Amnion formation
|The amniotic fold starts to form from posterior tissue of primitive streak bulging.
-Allantoic bud evident
-Gastrulation continues
-Primitive node visible
-Amnion begins to close
|-
|11
|7.5 (range 7.25-8)
Human carnegie stage: 9
|Formation of neural plate and presomites
|Amniotic cavity is sealed to form 3 cavities (amniotic cavity, exocoelom and ectoplacental cleft)
-Allantoic bud elongates
-Notochodal plate can be seen in the midline and subjacent to neural groove
-Head form from the enlargement of the rostral end of neural plate (early head fold)
-Formation of foregut pocket begins
|-
|}

=== Theiler stage 12-14 ===
{| border='1px'
!Theiler stage !!Embryonic age in Days Post Coitum (dpc) !!Stage characteristic !!Cell characteristics !! Number of somite pairs !!
|-
|12 a)
|8 (range 7.5-8.75)
Human carnegie stage: 9
|unturned embryo
-1st appearance of somite pairs
|allantois extends into exocoelom
-maxillary components of 1st brachial arch prominent
-visible preotic sulcus in 2-3 stomite embryo
-formation of cardiogenic plate begins
- foregut pocket visible
|1-4
|-
|12 b)
|8 (range 7.5-8.75)
|unturned embryo
- formation of somites 5-7
-abscent 2nd branchial arch
|prominent headfolds
-neural closure at site of 4th and 5th somites closing in caudal and rostral directions
-optic placodes visible with indentation of optic pits
-rapid development of heart rudiment
-allantois comes in contact with chorion
|5-7
|-
|13
|8.5 (range 8-9.25)
Human carnegie stage: 10
|turning of embryo at around 6-8 pairs
-3rd branchial arch absent
|1st branchial arch with maxillary and mandibular components
-2nd branchial arch visible
- regionalization of heart visible
-neural tube closure at point opposite outflow tract to proximal part of tail
-notocord and prepancreatic endoderm contact remaining
|8-12
|-
|14
|9 (range 8.5-9.75)
Human carnegie stage: 11
|anterior neuropore formation and closure (at 15-18 somite pairs)
-forelimb bud absent
|optic pit becomes more indented
-mandibular process of 1st branchial arch visible
-3rd branchial arch visible
-prominent ridge on lateral body wall at 8th-12th somite
|13-20
|
|-
|}

=== Theiler stages 15-20 ===

Table 3: Mouse embryonic stages from Theiler stage 15 to 20 ( somite stages)
{| border='1px'
!Theiler Stage!!Embryonic Age (dpc)!!Stage Characteristic!!Cell Characteristic!! Somite Number(pairs!!
|-
|15
|9.5 (range 9-10.25)
Human carnegie stage: 12
|Formation of Forelimb bud
-Posterior neuropore
|8-12th somite pair condensation of forelimb bud is visible

-Hind limb bud appears

-Forebrain vesicle division into telencephalic and diencephalic vesicles

-Lung development commences

-1st sign of Pancreas morphogenesis of dorsal pancreatic bud (22-25 somites).
|21-29
|-
|16
|10 (range 9.5-10.75)
Human carnegie stage: 13-15
|Caudal neuropore closes
-Hind limb bud (23rd-28th somite) and tail bud
|Concave 3rd and 4th branchial arches.
-Rathke's pouch formation

-Nasal processes formation.

-Ventral pancreatic bud appears
|30-34
|-
|17
|10.5 (range 10-11.25)
Human carnegie stage: 13-15
|Deep Lens Indentation
|Lens pit is deepened and has a narrowed outer opening.
-Physiological umbilical hernia present.

-1st branchial arch divides into maxillary and mandibular components.

-Advanced development of brain tube

-Tail elongates and thins
|35-39
|-
|18
|11 (range 10.5-11.25)
Human carnegie stage: 13-15
|Closure of Lens Vesicle
|Cervical somites no longer visible
-Brain rapidly grows

-Formation of nasal pit
|40-44
|-
|19
|11.5 (range 11-12.25)
Human carnegie stage: 16
|Lens vesicle separated completely from surface
–Closed and detached from ectoderm
|Well Defined eyes and their peripheral margins
-Forelimbs divided into two regions

-Proximal part of the future limb-girdle and 'arm'

-Peripheral part forming a circular or anterior footplate.

-Otic pit medial and lateral margins move together

-Auditory hillocks visible
|45-47
|-
|20
|12 (range 11.5-13)
Human carnegie stage: 17
|First sign of fingers
|Anterior footplate no longer circular (develops angles)
-Posterior footplate visible

-Pigmentation of retina visible

-Tongue and brain vesicles identifiable
|48-51
|-
|}

Talk:2009 Group Project 4

2009-09-28T06:56:27Z

Z3185685:

==peer reviewing==
--[[User:Z3217015|Mitchell Mathieson]] 09:39, 25 September 2009 (EST)Page looks good. I liked how there was heaps of information on the genetics and the current research (however, this was a bit too spread out maybe). There seems to be a lot of gaps in the text, so the formatting could be maybe tightened up. The references maybe should be formatted better, and there is repeated information (tables and text for stages), but I really like how clicking the image goes to another page with more information...that is cool. The drawings are cute as well. Overall very good, I think formatting was the downfall from that, but the information is top notch.

--[[User:Z3126328|Jin Lee]] 16:42, 26 September 2009 (EST) hellow group4~ very impressive assignment guys!well done! I really enjoyed reading your assignment. it was easy to read and the information was relevant. However, I found the formatting of the images and texts were too sqeezy. may be resize the images and line up with the relevant information. Also, I think the reference needs to be looked after as well. Overall, the contents of the assignment is very useful and interesting.

--[[User:Z3187802|Vishnnu Shanmugam]] 20:02, 26 September 2009 (EST)Congratulations mouse group on an excellent assignment. It is a real joy to read. One of the best features of the assignment is how it gets straight to the point with the use of sub headings “What did he do?” & “What did they find?”. Even the images used throughout the text are interesting, especially the fully labeled hand drawn images in the “staging” and “timeline” sections. Some ways to improve the assignment:

-There are some unnecessary graphs in the assignment such as “the average length of mouse embryo”, “number of cells” and “number of somites”. These could perhaps be combined into a single graph. It will also reduce the congested appearance of the assignment as it seems too densely packed with no particular focus.

- In current research section, it is advisable to reduce the number of research and focus on just a few but provide more comprehensive information on the background of the research, the findings and the relevance to human embryology. It currently contains too many different types of research that have described very briefly.

- Edit the "content" section at the top of the page as it's length seems to be getting out of control. It is perhaps better to exclude the sub headings “What did he do?” & “What did they find?” in the contents.

- The referencing in the text need to be completed as there are some sections well referenced and others with no referencing. see www.lc.unsw.edu.au/onlib/ref_apa.html for help with APA referencing

- A Glossary would also complement the text.

Overall a classy project, only some changes necessary

--[[User:Z3126345|Gang Liu]] 16:49, 27 September 2009 (EST)This is one of the better wikipage i have seen so far. It demonstrates not only extended literature research skill, but also an in-depth understanding of the topic. The content of this page has been consistent throughout. In addition, paragraphs are straigtforward and concise, and make the point. Detailed texts with accessory graphics are appropriate in here. In paticular, history section. It describes the model use in terms of details of experiment, and results of experiment. Stages and timeline are very self-explanatory and visually enhanced.

This project can be improved by considering the following points.

*Lack of glossary list. Need to provide meaning of words such as "polyestrous", "oocyte", "Ectoderm", "endoderm", etc;

*Reformat stages section. I found this section a bit "busy". Might considering resize the pictures.

Last few words. I have learnt from this page that mouse has the same size genome as the human genome; Mouse genes can be easily manipulated and studied; Mouse a high degree of homogeny with humans. Well done!

--[[User:Z3217686|Thomas Dangerfield]] 14:12, 28 September 2009 (EST)Hey guys! Wow so much info first off! Not entirely sure we need to know about everyone involved in the history, maybe could have collaborated and joined people together or possibly even left certain people out. To me, the whole page is like how mark described, with everything all one great smudge of info with no real formatting or sequence or continuation. It was just kind of like an overload and reading it was a little difficult at some stages. Also corresponding the images in the timeline could have been included in the text.

Also I think your numbering of figures is a little off in the timeline section, with figures 1-4 on the right and then you have figures 4-7 describing stages 12-14. Just seems that there is two figure 4's for two different images.

Love the large amount of research and information, but could just work on your presentation and you'll do fine! Great work guys!

Hey guys! Overall a very nice assignment with a great deal of information! You can tell you guys did a lot of research. The contents are massive! Maybe you could cut this down and not use so many subheadings such as “what did they do?”, “what did they find?” and only have a subheading for each researcher. The introduction is well written. The history of model use has some really good information. My only criticism in this section is that there are a lot of gaps and blank spaces. You just need to delete all the spaces. The staging section showed a lot of research and effort. Well done!! The only thing is, is it a bit too much? There are a lot of tables and images that it was hard to keep track. Maybe this could be set out differently and made to look less busy. The timeline of development is fantastic and set out really well. It is very easy to understand and the drawings are great! Once again the current research is very spread out with lots of spaces. Also adding a glossary may help the readers in understanding the text. GREAT JOB!

----

--[[User:S8600021|Mark Hill]] 01:46, 8 September 2009 (EST) Well the content is there now, but what a mess, and I am not just talking about the formatting problem which can be easily fixed, you have no structure to your project, its not a matter of throwing everything at a wall and seeing what sticks. Work together for an integrated coverage. Timeline of development, is not the way to start your page with a huge table of data.

--[[User:S8600021|Mark Hill]] 08:43, 21 August 2009 (EST) OK guys, time to see some actual content uploaded on both your discussion and project pages.

* Timeline of Development - how long (Emily)
* Staging - are there species specific staging, what occurs when (Elide)
* History of Model Use - when was it first used, what embryology research (Begum)
* Genetics - chromosome number, sequencing (Angama)
* Current Embryology Research - research papers and findings (All)

Here is a link for timeline
[http://books.google.com.au/books?id=XLIarRWHikAC&pg=PT199&lpg=PT199&dq=mouse+embryo+development+timeline&source=bl&ots=fobLBRiacx&sig=cK4cuZah6Ksczs3o8v4NXQqoAyk&hl=en&ei=rGB6SvTHMMmIkAXB_piAAw&sa=X&oi=book_result&ct=result&resnum=3#v=onepage&q=&f=false
]

link for the mouse brain development timeline http://en.wikipedia.org/wiki/Mouse_brain_development_timeline

hey guys there is another interesting link about mouse development http://mouseatlas.caltech.edu/index_content.html

Hey Emily. The link below has a timeline that you can check out in your spare time. Begum.
[http://books.google.com.au/books?id=4juoa5xMs8oC&pg=PA31&lpg=PA31&dq=mouse+embryology&source=bl&ots=9tJAfRG4R6&sig=hjR5Zs-sL1sCW5FY8FnR5TMaUk0&hl=en&ei=LuuMSr_aCNjakAX714icDA&sa=X&oi=book_result&ct=result&resnum=9#v=onepage&q=mouse%20embryology&f=false]

Hi girls,
here is a link to a text book about mouse embryology it looks pretty good. hope it can help
[http://books.google.com.au/books?id=4juoa5xMs8oC&printsec=frontcover&dq=mouse+development&source=gbs_similarbooks_r&cad=2#v=onepage&q=mouse%20development&f=false]
let me know if the link doesnt work. Ive been working on the main page, so have a look and tell me what you think, Also what are we doing about references? If we have used information but put it in our own words do we need to put in text citations,or do we just reference the journal at the end? I just want to be very careful. Thanks!

Hey Elide, i think your work is looking really good. its very easy to read and understand. keep going!!!! emily

hey everyone,
I have uploaded some of my timeline work. I'm not sure if I've gone into to much detail or not and also on how is best to present the timeline. It is fairly basic and definately needs some work - especially on presentation, grammar, etc. let me know what you think.
Emily

good site for stages or timeline- atlas of pictures of stages- The Edinburgh Mouse Atlas Project [http://genex.hgu.mrc.ac.uk/]

Hello girls, it's Begum. I put some info under the history section. Wanted to let you all know that I've got a fair bit of info, and I will do my part as best as I can. Btw Emily, I think maybe dot from would be best for you, but if you can use those lines that I was talking to you about on Wednesday, that would be great...I know it's hard.

hey everyone, i have put some info under the genetics heading and some under research. I am still struggling to find the appropriate info related to the topic of genetics because there is alot of info abt the different types of stains used in labarotories but not the genetics. I emailed Dr.Hill and have asked him what to include in my section specifically,hopefully he will help. So far i have just started it needs alot of more work to be done,girls just read thru my section n leme know wt u think of it. have a nice weekend everyone. Angama.

Hi girls!
Begum, you history info is really good. If very interesting! I really like how you are doing it in order of dates of discovery and what they did, what they found etc! Cant wait to know more.
Angama, your doing well! it sounds like your finding the info hard to get. I'll keep an eye out for you! If your stuck on what you sound be doing then i might have a few ideas. I remember Mark Hill saying that you should compare the genome to the humans genome. so maybe if the genome is the same size as the humans, could you descibe similarities or differences? I know that there is a link to the mouse genome on the mouse web page he gave us ( next to the discussion link). Are you just ment to list the mouse genome sequence? could you go into what genes code what, eg which one codes for the sex linked gene, is it the X and Y gene etc? hopefully Mark gives you some ideas.
well as you might have noticed i've been adding to my stages. the only thing is im worried about there being too much info up there. basically ive tried to get all the info available included in my stages to make sure i cover everything, and then later i'll go over it all and edit and polish it up a bit. Ive done some drawings to the best of my ability, but i can scrap them if you all think they arnt professional enough. just thought i'd try to present the information differently. let me know if you think i'm including too much information. i think i'm having the same problem as you begum, there is lots of info! Elide

Thanks Elide. I'm trying. (Again, loved the artwork!)Btw, Emily, I had a think about your section and I think it might be too much 'clicking' back-and-forth if we link the displayed pic to the 'info' page. Don't stress, you've got the info (heaps which is excellent) but make sure you get some pictures soon so we can start drawing (I'm helping with the drawings as well ok). Mark said 'Nature' and 'Science' have useable images so lets make that our start.
BTW, I will be using the question mark symbol(???) so I don't forget to reference. Begum

Hey everyone, I have found an online text book. it has a chapter on genetics and history and a lot of other stuff. [http://books.google.com.au/books?id=Vt6nUmz1yEQC&pg=RA1-PA207&dq=mouse+development+anatomy&client=firefox-a#v=onepage&q=mouse%20development%20anatomy&f=false] Emily

Hey girls. If you've seen my section, the info is not on the main page, but linked to another page. I thought that it might make everything look more neat. I thought we could all do it like that. It's just an idea. Something different. Maybe we could have something on the main page (picture of a mouse). Your thoughts everybody? Begum

hey begum, ur work looks really good. i like the idea of linking the work to another page. - we don't have to worry about to much info being on the front page and it gives people to option of viewing the work if they want to. ive been working on drawings, i'll show them to you next week but am not sure how to upload them at the moment. Emily

Thanks! That sounds great that you like the idea. About the photos that you are drawing, if there by hand, you can scan them somehow. But overall,
1. click 'Upload File' on the left hand side of this page
2. New page comes up: click 'Browse' and choose your file that you want to upload.
3. Name it (under the Browse button)
NOTE: write down what you named the file as because like Elide says "...it's going to be lost in space!..."
4. Write down info/comments (like who is the author (YOU), and if the drawing is based on a picture)
5. UPLOAD!
6. Go to your section and just normally type this down to the area you want the picture to be seen:
[[image:THE NAME THAT YOU SAVED THE FILE UNDER.jpg|thumb|200px|right|WHAT YOU WANT THE FILE NAME TO VISUALLY COME UP AS]]

Your thoughts Angama and Elide? (about the linking of our sections to separate pages?) Begum.

Oh and another thing:
What do you girls think about my page, I've got a heading for each DATE and underneath each there are further subheadings (e.g. 'What did he do?'. Should I change them to just text, I mean, does it look messy with sub-sub-headings? Begum.

wow girls! great work.. okay so i asked mark about a new page and he said to avoid it because our info is meant to be on our one page. he said if there is extra information on what we wanted to say but is too much for the main page then have a link to our discussion page. (which is what im going to do) Begum your new page is fantastic!! you have done lots of work! but why dont you just put it on our main page? also girls i think we are getting too carried away with info. just keep it simple! i'm sorry i havent been around this week to work on it but i plan to get going asap. just fixing up some things, summarising, writing introductions etc.
did you all read his note about slabbing info onto our page?? how about some introductions, and sentences to ease ourselves into the content. planning on trying to work on that now anyway..

also lets get the information flowing. why dont we go intro, history of model use, stages, timeline, genetics, then current use.. what do you all think?

hey, i thing that that sounds like a good, logical way to do the page. i've finished the drawings, just need to upload them. About the timeline information, is there anything specific that i should include. the stuff that is on the page is a little vague and so i need some advice as to what are key points that i should include. i know that the drawing are very simplistic, let me know wjat you think about them. ive put one up below. i just need a way to link it to text. emily

Thanks Elide. You know, I think that's a great idea. Have it all on one page, seems less 'diverging...', seems more COMPLETE. I love the ORDER as well. I'll fix all that up!

Hey girls, please have a look at what i've done on the timeline. the images are all hand drawn based upon the text: 'the house mouse'. if anyone could give me any ideas on how best to present the pictures - which would be better - next to or below the text? keep in mind that it is incomplete and there is an illustration for each day of development (i.e. 19 in total). if you think that is too many let me know, some may be similar to Elide's ones. Also, do you think i should put some colour into the drawings? Emily

I love your work Emily. All you need to do is put the info on the growth of the mouse that is on the main page, onto the page with the graph of the growth of the mouse embryo...we talked about that before any way-AND I think your parts finished! Begum.
Angama, I added something to the end of your section that I thought was interesting. Have a look. And are you mentioning manipulation and 'shut-down' of the genes in your section?? Begum.
To everyone, apparently ''Mus Musculus'' is the scientific name of the common house mouse, not the mouse. I was thinking of editing that.

HEY EVERYONE! well i've added in some pictures just to make it look more visual, change them if you have better ones.. and i'm going to be working on the current research section tommorow. oh i also added some graphs like we thought of for emilys section.. so i think my section is finished finally! what do you think? can i just say, I think the whole thing looks great! you girls have been a pleasure to work with! :) Thanks so much!!

hi girls, i am sorry..i have been very busy during the mid-sem break and i know we all had our exams and assignments due. but i was having some issues in my family and also the exams and assignments so didnt really had the chance to read wat u girls have got on the main page. i just finished reading thru it and it looks amazing..WELL DONE GIRLS!! you all have done a marvellous job...Eldie and Begum thanks for suggesting some main points to add for the genetics.i am currently working on it.. hopefully tonight i will have all the information on the page..Begum i love how you have presented alot of info into a very easy and understandable way..it makes so much sense..n it looks very nice with the pictures. Eldie and Emily great amount of work and the pictures and the graphs are superb. i just had a look to other groups pages. n i think so far our page looks very interesting with concise info n amazing pictures. n Begum yes i read what you have added thanks for tht..i will cu girls around..gudluck everyone. cheers. Angama.

Girls can you please help me out.. i am so annoyed..
like rite now i was typing some info and when i clicked to save.
it says "conflict" so i think some one else is also editing
the page at the same time that i am. and i lost all my work..arghh..
so which means i have to type it all again.
is there any other way that it tells me that someone else
is also using it so i dont click on save or even preview
because when i do tht i lost all the work tht i had.
If anyone knows please let me know. thanks. Angama.

Current research : I have put some information in the current research part. not sure where they should be put. Begum, as discussed you can edit it or place it in its appropriate place.

Don't stress Angama at all, now you know, it will be over soon. Uploading it easy:

1. click 'Upload File' on the left hand side of this page

2. New page comes up: click 'Browse' and choose your file that you want to upload.

3. Name it (under the Browse button) NOTE: write down what you named the file as because like Elide says "...it's going to be lost in space!..."

4. Write down info/comments (like who is the author (YOU), and if the drawing is based on a picture)

5. UPLOAD! 6. Go to your section and just normally type this down to the area you want the picture to be seen:

It's easier than it is typed! Of you still have problems I will be at the embryo lab, of there is exams there the ANAT LAB opposite to it, if not Level 3 library computers.

[http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=19538749| maternal diabetes alters transcriptional programs in the developing embryo], [http://www.ncbi.nlm.nih.gov/pubmed/19414407?ordinalpos=35&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum|Abnormal mammary gland development in MMTV-CBLC transgenic mouse], [http://www.ncbi.nlm.nih.gov/pubmed/19394325?ordinalpos=40&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum|Sonic hedgehog signalling inhibits palatogenesis and arrests tooth development in a mouse model of the nevoid basal cell carcinoma syndrome.], [http://www.ncbi.nlm.nih.gov/pubmed/19358209?ordinalpos=55&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum| Fibroblast growth factor 18 gives growth and directional cues to airway cartilage.]

Hi girls, i think i have completed my section. could you all please just read thru it and leme know wat you think of it. i did it to the best of my ability. Hopefully you will all like it if you girls think therez anything more to add or to delete leme know..thanks. gudluck girls. Angama.

Angama your work is fantastic! Thanks so much! im sorry i wasnt around to help you with the problems. hope it went okay. your info is perfect! im very happy with our page! lets hope everyone else is :)

I love it Angama, good work! And the pictures you uploaded are very interesting. Cool. Awesome. Your done!! Begum.

Thanks Begum :) Girls gudluck and cu all tomorrow. Angama.

== Staging of mouse embryo development ==

===Theiler stage 6-11===

{| border='1px'
|+ Table 2: Mouse embryonic staging from blastocyst implantation to pre-somite formation (Theiler stages 6 to 11)
! Theiler Stage !! Embryonic age in Days Post Coitum (dpc) !! Stage Characteristic !! Cell characteristics !!
|-
|6
|4.5 (range 4-5.5)
Human carnegie stage: 4
|Attachment of blastocyst
-Implantation
|Embryonic Endoderm present covering the blastocoelic cells of the inner cell mass.
|-
|7
|5 (range 4.5-6)
Human carnegie stage: 5
|Implantation
-Egg cylinder formation

-Ectoplacental cone
|Inner cell mass increases in size
-Epiblast formation (enlarged mass)

-Proximal cells are cuboidal in shape

-Mural trophectoderm is lined by primary endoderm
|-
|8
|6 (range 5-6.5)
Human carnegie stage: 5
|Differentiation of egg cylinder into embryonic and extra-embryonic regions
-Pro-amniotic cavity formation
|Trophoblast giant cells invade maternal tissue
-Maternal blood invades the ectoplacental cone

-Reichert's membrane appears

-Implantation site is 2x3mm
|-
|9 a)
|Pre-streak
|Advanced Endometrial and egg cylinder stage
-First evidence of embryonic axis
|Morphological difference can be seen between embryonic and extra-embryonic ectoderm
-Maternal blood further invades ectoplacental cone

-Uterine crypts lose their original lumen
|-
|9 b)
|Early streak
|Gastrulation begins (later in stage)
|First mesodermal cells produced
|-
|10 a)
|7 (range 6.5-7.5)
Mid streak to late streak
Human carnegie stage: 8
|Amnion formation
|The amniotic fold starts to form from posterior tissue of primitive streak bulging.
-Allantoic bud evident
-Gastrulation continues
-Primitive node visible
-Amnion begins to close
|-
|11
|7.5 (range 7.25-8)
Human carnegie stage: 9
|Formation of neural plate and presomites
|Amniotic cavity is sealed to form 3 cavities (amniotic cavity, exocoelom and ectoplacental cleft)
-Allantoic bud elongates
-Notochodal plate can be seen in the midline and subjacent to neural groove
-Head form from the enlargement of the rostral end of neural plate (early head fold)
-Formation of foregut pocket begins
|-
|}

=== Theiler stage 12-14 ===
{| border='1px'
!Theiler stage !!Embryonic age in Days Post Coitum (dpc) !!Stage characteristic !!Cell characteristics !! Number of somite pairs !!
|-
|12 a)
|8 (range 7.5-8.75)
Human carnegie stage: 9
|unturned embryo
-1st appearance of somite pairs
|allantois extends into exocoelom
-maxillary components of 1st brachial arch prominent
-visible preotic sulcus in 2-3 stomite embryo
-formation of cardiogenic plate begins
- foregut pocket visible
|1-4
|-
|12 b)
|8 (range 7.5-8.75)
|unturned embryo
- formation of somites 5-7
-abscent 2nd branchial arch
|prominent headfolds
-neural closure at site of 4th and 5th somites closing in caudal and rostral directions
-optic placodes visible with indentation of optic pits
-rapid development of heart rudiment
-allantois comes in contact with chorion
|5-7
|-
|13
|8.5 (range 8-9.25)
Human carnegie stage: 10
|turning of embryo at around 6-8 pairs
-3rd branchial arch absent
|1st branchial arch with maxillary and mandibular components
-2nd branchial arch visible
- regionalization of heart visible
-neural tube closure at point opposite outflow tract to proximal part of tail
-notocord and prepancreatic endoderm contact remaining
|8-12
|-
|14
|9 (range 8.5-9.75)
Human carnegie stage: 11
|anterior neuropore formation and closure (at 15-18 somite pairs)
-forelimb bud absent
|optic pit becomes more indented
-mandibular process of 1st branchial arch visible
-3rd branchial arch visible
-prominent ridge on lateral body wall at 8th-12th somite
|13-20
|
|-
|}

=== Theiler stages 15-20 ===

Table 3: Mouse embryonic stages from Theiler stage 15 to 20 ( somite stages)
{| border='1px'
!Theiler Stage!!Embryonic Age (dpc)!!Stage Characteristic!!Cell Characteristic!! Somite Number(pairs!!
|-
|15
|9.5 (range 9-10.25)
Human carnegie stage: 12
|Formation of Forelimb bud
-Posterior neuropore
|8-12th somite pair condensation of forelimb bud is visible

-Hind limb bud appears

-Forebrain vesicle division into telencephalic and diencephalic vesicles

-Lung development commences

-1st sign of Pancreas morphogenesis of dorsal pancreatic bud (22-25 somites).
|21-29
|-
|16
|10 (range 9.5-10.75)
Human carnegie stage: 13-15
|Caudal neuropore closes
-Hind limb bud (23rd-28th somite) and tail bud
|Concave 3rd and 4th branchial arches.
-Rathke's pouch formation

-Nasal processes formation.

-Ventral pancreatic bud appears
|30-34
|-
|17
|10.5 (range 10-11.25)
Human carnegie stage: 13-15
|Deep Lens Indentation
|Lens pit is deepened and has a narrowed outer opening.
-Physiological umbilical hernia present.

-1st branchial arch divides into maxillary and mandibular components.

-Advanced development of brain tube

-Tail elongates and thins
|35-39
|-
|18
|11 (range 10.5-11.25)
Human carnegie stage: 13-15
|Closure of Lens Vesicle
|Cervical somites no longer visible
-Brain rapidly grows

-Formation of nasal pit
|40-44
|-
|19
|11.5 (range 11-12.25)
Human carnegie stage: 16
|Lens vesicle separated completely from surface
–Closed and detached from ectoderm
|Well Defined eyes and their peripheral margins
-Forelimbs divided into two regions

-Proximal part of the future limb-girdle and 'arm'

-Peripheral part forming a circular or anterior footplate.

-Otic pit medial and lateral margins move together

-Auditory hillocks visible
|45-47
|-
|20
|12 (range 11.5-13)
Human carnegie stage: 17
|First sign of fingers
|Anterior footplate no longer circular (develops angles)
-Posterior footplate visible

-Pigmentation of retina visible

-Tongue and brain vesicles identifiable
|48-51
|-
|}

Talk:2009 Group Project 3

2009-09-28T06:08:29Z

Z3185685:

==peer reviewing==

--[[User:Z3217015|Mitchell Mathieson]] 09:42, 25 September 2009 (EST)Overall very very nice. Was nice and succinct, and easy to read. The information was relevant, and the current research interesting. Maybe the stages on different pages was a bit difficult to read; I would have liked to have seen at least a bit of information on the main page, which expands to more on your secondary page. The formatting of the references I think needs to be looked at maybe.

--[[User:Z3224449|Elide Newton]] 14:38, 26 September 2009 (EST) HELLO GROUP 3: Congratulations on a great assignment. Each section is equally proportioned, and well represented visually. My one point of constructive criticism would be to the section on current research. Your information is great, as it shows how the zebrafish is being used as a model for different areas of research. The one thing which would improve this would be to include the dates of these research papers, just so the reader can know how recent the work is. maybe introduce the research as Person et al (2009) has used the zebrafish to.... Also are there any pictures on this research? Just because research language is so technical, some pictures would break it up. Hope this helps you group 3.

--[[User:Z3126328|Jin Lee]] 16:06, 26 September 2009 (EST) congratulations to Group3! this is a really great assignment. overall, all the sections are well represented visually.
I liked the history part mostly! easy to read! Maybe the current research section can be improved by adding some images and relevant links. I found zebrafish is very interesting!thank you

--[[User:Z3187802|Vishnnu Shanmugam]] 19:32, 26 September 2009 (EST)Well done Zebra fish group. You've put together a well balanced assignment. The images under "Timeline and Stages of Embryonic Development" are impressive, really make the assignment stand out and the text flows nicely. I also noticed the links to researchers and research laboratories have been made throughout the text and because they are under specific headings, the reader will know what the information in the link will focus on. Additions to improve the assignment:

- there is some irrelevant images in the the text; the images "A 1981 issue of Nature journal" & "Development.jpg" are Unnecessary and could be replaced with others that support the text or summarize complex processes. (eg. motor neuron development in zebrafish or a time line showing the evolution in the use of zebrafish). The second image "Development.jpg" is better replaced with the image "A Zebrafish Pigment Mutant" as it is relevant to the text. The current research does not mension or explain the Zebrafish Pigment Mutant and thus is Unnecessary there.

- The Genetics section could do with an image of zebrafish chromosomes. This can be a simple hand drawn diagram and can be compared to the human chromosomal makeup.

- The current research section could use a description of how zebrafish research has impacted human embryology.

-The assignment needs to be properly referenced. see www.lc.unsw.edu.au/onlib/ref_apa.html for help with APA referencing.

- A Glossary would also complement the text.

Overall very impressive, only needs minor editing.

-[[User:Z3252340|Emily Wong]] 11:04, 27 September 2009 (EST) To begin with, you have done a great job group 3. It is a well researched, structured and organized page. The student contribution to the work is fairly even. The condensation of the written content is done well, with the combining of the timeline and stages in one section and extensive use of visual representation. However, information is not provided when clicking on the pictures as to what is in them. A description or explanation of what is occurring in each stage or at each time point would improve this project. Some of the images used have not been referenced properly in the image pages. Referencing is good and an extensive reference list has been provided. The content provided is very detailed by still brief and relevant to each section. This project could also be improved by adding some examples of current research and also referencing information throughout the written content. Perhaps an inclusion of a Pubmed search link in the current research section would be a good idea so that viewers can see what other research has been done using the zebrafish.

--[[User:Z3126345|Gang Liu]] 16:17, 27 September 2009 (EST)This is a very informative, well constructed and concise wikipage. It has demonstrated consistency throughout the page. There are a number of major subheadings have been included history, timeline, development, genetics and current embryology research as well as hand drawing. In addition, it has demonstrated extended research of literatures. For example, by dividing the history section in a number of subheadings such as "in the beginning", "Charles Kimmel", "Hesitations", etc. This has indicates the in-depth understanding of zebrafish embryo model use. It allows the reader to appreciate story behind the experiment, as well as scientists' thinking process and thoughts. "...there was no gene cloning and little understanding about genes, making the whole zebrafish project almost a gamble to follow through with. This put much strain on the funding given to Streisinger and the credibility of his work...".

The graphic delivery of timeline and stages are very self-explanatory and powerful. A picture explains a thousand words. It makes the section easy to follow, and interesting to read also.

However, this project can be improved by considering the following points.

*I found genetic and current embryology section were very lengthy and wordy, and lack of pictures. In addition, referencing in these two sections were inconsistent with previous sections;

*Lack of glossary list. Such as "oxidative phosphrylation", "N-ethyl-N-nitrosourea (ENU)", "Diploid" and "Haploid" need to provide meanings;

*Inconsistent referencing. Name of author need to keep in alphabetical order. Also articles and web based materials are mixed. The first five references were inconsistent with the rest in style;

Last few words. I enjoyed reading it, learned something out of it. Big thumb up for me.

--[[User:Z3217686|Thomas Dangerfield]] 13:54, 28 September 2009 (EST)Well done guys! Nice, visually stimulating assignment! Just a few points about possibly having a little more written info on the timeline, just to help explain what is in each image. Also some pictures of the chromosomes of the zebrafish would be a handy visual tool. This may just be a little picky, but i notice that you have a few heading issues:

- Beginning not Begining. (In the begining..)

- Genetics of the Zebrafish and Embryology, and the you have a 'Genetics and Embryology' a couple of headings down which seems a little unnecessary.

Just as a hint on being thorough, maybe a glossary could have been included, as well as formatting for your references. Still, a well presented assignment has been done here!

--[[User:Z3185685|Sumaiya Rahman]] 16:06, 28 September 2009 (EST) Hey guys. Well done on the assignment overall. It was interesting to read about the zebrafish. The page was well introduced. It is good that you broke up the information using subheadings. This makes the page a lot easier to read as it breaks up the big slabs of text. I think it has been mentioned, but there are a couple of spelling mistakes. Also the sentence “This however did not affect Neurologists such as Kimmel as they were not much worried about the relevance of their work” needs to be fixed up. This is only a minor error. The history section could look a little bit less messy if the pictures were placed on the same side. “The fish is a frog... is a chicken... is a mouse” picture is very cute! But maybe a little bit too big because we need to scroll across to see it (or is that just me?). You have some great references and links and a great timetable and stages section with good visuals. The genetics and current research sections have a lot of text, maybe finding a way of making these sections more visually appealing would help the readers. Also including a glossary would help. Overall nice work!

----

--[[User:S8600021|Mark Hill]] 01:44, 8 September 2009 (EST) A single image of a fish, well that really gets across the message of zebrafish development, interpret the information you have read and put it into a format that will interest the reader.

ZebraFish - Zebrafish are really cool...

I'm happy with zebrafish... never heard of them but they sound interesting :) what does everyone else think? ...Gaby Pinget

Great, who else is in our group then... Oh and i'm Sal by the way

Ok so i'm not sure who the other two are because i don't know your number but just for reference my number is z3218657.
I found this cool website with some pictures of Zebrafish embryo's developing... its pretty cool...

http://www.cas.vanderbilt.edu/bioimages/animals/danrer/zfish-devel.htm

and this website shows all the stages and times and such good for a timeline

http://zfin.org/zf_info/zfbook/stages/stages.html

Research Topics for this week:
- Timeline and Staging (Sal)
- History of Model Use (Gaby)
- Genetics (Bronwyn)
- Current Embryology Research (Jo)
--> Share what we've learnt with the group next session.

Hey Guys I have a lot of info... and i don't think i should post it all up here because there is a lot of stuff... Mainly all about the Staging though. I am going to put up a summary of the different stages. The website i gave you before ZFIN is the zebrafish database of model organisms. its great!

'''Zygote Period''' – Lasts for 0-0.75hours
Transition of one cell to two cells.
Fertilisation occurs activating cytoplastimic movement. The animal poles within the cell segregate the blastodisc from the yolk cytoplasm. Segregation continues into the cleavage staging.

'''Cleavage Period''' – Lasts for 0.75-2.25 hours
Transition from two cells to 128 cells
After the first cleavage the blastocysts division is approx every 15 minutes.

'''Blastula Period''' – Lasts for 2.25-5.25 hours
Transition from 128 cells to 50% epibolby
“Epiboly, beginning in the late blastula (Solnica-Krezel and Driever, 1994), is the thinning and spreading of both the YSL and the blastodisc over the yolk cell, as you might model by pulling a knitted ski cap over your head” – Direct quote from the ZFIN website

'''Gastrula Period''' – Lasts for 5.25-10.33 hours
Transition from 50% epibolby to 1-4 somites
The gastrula period ends when epiboly is complete, and the tail bud has formed. Here each germ layer (endoderm, mesoderm, ectoderm) is put in the right place so that bodily organs and tissues can form in the correct locations.

'''Segmentation period''' – Lasts from 10.33 – 24 hours
Transistion from 1-4 somites to Prim-5
Here dermis, vertebrae and skeletal muscle are formed

'''Pharyngula Period''' – Lasts from 24 – 48 hours
Transition from Prim 5 to Long-pec
The body axis begins to straighten and the fins begin to develop.

http://www.youtube.com/watch?v=0hGT667ktTw

'''Hatching Peroid''' – Last from 48 to 72hours
Transitions from Long-Pec to Protruding-mouth
In this period, primary organ systems develop and cartilage development begins.

'''Larval Period''' – Lasts from 72hours to 30days
transition from Protruding-mouth to Day 30-44
The pectoral fin continues to develop and the internal organs become more complex. Development continues.

'''Juvenille Period''' – Lasts from 30-44 days
Here adult fins and pigments as well as 12 teeth develop.

'''AdultPeriod''' – Lasts90days to 2 years
Full Breeding Adult.

http://www.youtube.com/watch?v=5ygcu9BRXI0 - Zebrafish heart beating!

http://www.youtube.com/watch?v=TbErcmhzUSY - alcohol effects on Zebrafish embryo

Websites used
http://dev.biologists.org/cgi/content/abstract/dev.022673v1

http://www.zfic.org/classroom%20experiments/stagingindex.html

http://zfin.org/zf_info/zfbook/stages/stages.html

Hey! This is a really good site with a bunch of links relating to the different areas we have to research:
http://www.sanger.ac.uk/modelorgs/zebrafish.shtml

Hey guys.... Ive found a really good picture of the zebrafish embryo development (like the human one) but I dont know how to put it up, was thinking it might be better if it was actually on the page rather than a link to get the picture. JO

well I think that I just uploaded a picture but I have no idea where to... wow I'm so lost... Maybe that's a good thing because I have a feeling that it was copy right protected... DAMN COPY RIGHT ah ha ha

Hey all, all the websites that i have put up on this page have really good images... I have emailed the three of them and asked if it was ok if i used them to put up on here and i am awaiting a reply so
hopefully they will let us use them. Also i am having a tonne and a half of trouble uploading a InDesign Timeline image i created of the timeline and also having some issues with the net so i might
bring them to class and see if the computers there are readable other wise i am screwed and will just have to start all over again. I have a more complete Timeline and Staging format that i have
created as well. I'll put that up when i try and upload the image again. Peace. - Sal

Hey Hey So I got permission from Judy Cebra-Thomas to use all her images on her website which are each stage of development - YAY we just have to accredit them. So today apart from working on
unwinding my InDesign TImeline and putting the info up in bullets i am going to start to figure out whats happening in all the images and try an upload them onto the site so hopefully tomorrow we
will have an almost finished timeline and staging section! - Sal

Right so I've posted a link to the current sequencing status on the genetics part of our site. This updates pretty much everyday so I will be able to update ours right before submission so we have up-to-date info. This is however a minor detail so I'm writing it here to help us all remember! :) thanks

'''Hey guys!! please read this: I put up pictures which are really just to make it look pretty rather than add any info. Can you please tell me if you think they're stupid or not serious enough? I promise that I wont be offended! I understand if any of you think that we should take our assignment more seriously than that... it's just hard to find images for a history of zebrafish use!'''

I dont really get the light bulb lol. Sally were u able to get the embryo stage images as a link to the info as u wanted???? I think its a really good idea if we could do it, i think it might be a matter of asking someone who's actually good with computers to do it lol. Im still complying info for the current research section, currently in qld but i wanna have it up hopefully by this week, at least part of it anyways. Im gonna try n get some pictures but every place that ive asked think im an actual doctor lol so its been a bit hard.

Ok so not quite sure how to do the linking but i might just make it all link off the page into separate little pages... does that make sense??? Probably not but i can try explain it better on thursday. The
images take me 1.5hours each to upload because i have to make the image in indesign, Grab it and then transform the image to a PNG file as that is one that this website allows for uploading! So they
are coming up but ever so slowly! When i got permission to use the images i just told them I was a student studying Advance Science from UNSW. I was enrolled in an embryology course there where
we were doing an assignment on the Embryology of Zebrafish. Could i please use your images with referencing and a link to your webpage or document. Thats kind of what i said! i'm hoping to have it
all up and ready on thursday but might have to finish it friday night as have friends down from QLD that tend to make my place messy and have a house inspection on that ARVO!!! - Cheers SAL

Hey Sally, just so u know. I moved the websites you used to the references section so it didnt seem odd to keep it after ur info.

Hey Sally, we were thinkin about whether or not we could mix the timeline with the stages, so we thought that maybe if on the actual page we had the timeline with the pictures, then by clicking on the pictures there would be the info that u got or maybe even putting it all into a table so the pictures & info are more integrated.

Hey guys sorry i wasn't in class yesterday i had a funeral. What i was thinking of doing was actually moving all the data off the page and you click on it to go to another page which as all the info! but
the idea of clicking on the picture and going to it sounds great. One flaw is that is it ok if i use the pictures twice because i have been cutting, altering, adding text and flattening the images so that
they have a caption of what is happening. If i just cut another image to show each stage and then you click on that to go to it i think that could be cool as long as when you open the next page it still
has the information and the image with the caption of what is occurring! Hope thats ok. I will work on it all tonight and hopefully finish. Its taking a lot more time than expect sorry!Sal

hey Guys so I don't know if you guys have checked the website out yet but i have been working on it today! I continued what i was doing with the linked page and have also drawn my own diagrams
which are colour coded and easy for people to understand what is going on during the stages. I thought it looked cool. I haven't finished yet - a few more periods to go but i can't look at the screen
any more so i will do some on tuesday night! Hope thats ok. Just wondering though about the Nature article images above it kind of comes across the screen and i was wondering if we could somehow
move the image a little higher or enter down some spaces so that the timelines section is lower and the nature article doesn't come over the images pushing the table to the left! Let me know what you
all think. Sal

Hey Sal, your part of the project looks great! I really like the idea of clicking onto another page to get the info. works really really well and it's really easy to understand. As for the size of the picture obscuring your section, I think that you already thumbnailed it and it looks fine. Also, do you know how to put a youtube video onto the webpage? I was able to for a project in another class and it looked good but that was much easier because it had a link to a bunch of plug ins i could use. If anyone has any ideas please let me know! Gaby

Hey Sally, ur part looks awesome!!! Everyone done forget about your references...ive tried making the ones there so far look like it was done by one person lol. I dont know how to do the youtube clip thing but i have one too, was thinking maybe we should have a section for helpful links or do u think we should just put the links in with watever section its assiciated with. Wat do u guys think??? Jo

Hmm I was just thinking that the best thing to do was to put up the links strait after whatever they're associated with, that way they are supplimentary to what the reader is looking at rather than random extras at the end. That'll prob work best, right? Gaby

Thanks guys I've put a tonne of effort in so hope it pays off! I was going to fix up the references (cause they just have my websites without being real references) but it took me a lot longer than i thought for the images as you
can see its 5am. Nice. Yes i think linking the videos with the relevant parts is best. I have added links to videos throughout my section. Also I have made it so that when you put your mouse over the images it comes up with its own
reference/copy right info. Also when adding a link to another website its best to name the website instead of having just the web address. Its really easy if you don't know how and i can show you how to fix them up. When we get our
feedback from the other groups we can add and so forth before the project is actually marked which is really great. I think we need more info with the Genetics part but i figure bron is doing that tomorrow! Jo I really love your
sections pics and info it great and to the point!Gaby, yeah i did move it hope thats ok. I do have one question though and not meaning to hurt your feelings but i'm not that keen on the drawn image of the bird,fish,frog and mouse.
It doesn't really fit. Sorry, I mean obviously the decision is up to you, but i think it just looks a bit odd in the middle of the page because it you see it first and think , what? That was just some of the other feedback i got
from some of my friends that i asked to check out the website and see how they could maneuver around it. So that's my major spiel. Catch ya tomorrow. Sal

Talk:2009 Group Project 3

2009-09-28T06:06:52Z

Z3185685:

==peer reviewing==

--[[User:Z3217015|Mitchell Mathieson]] 09:42, 25 September 2009 (EST)Overall very very nice. Was nice and succinct, and easy to read. The information was relevant, and the current research interesting. Maybe the stages on different pages was a bit difficult to read; I would have liked to have seen at least a bit of information on the main page, which expands to more on your secondary page. The formatting of the references I think needs to be looked at maybe.

--[[User:Z3224449|Elide Newton]] 14:38, 26 September 2009 (EST) HELLO GROUP 3: Congratulations on a great assignment. Each section is equally proportioned, and well represented visually. My one point of constructive criticism would be to the section on current research. Your information is great, as it shows how the zebrafish is being used as a model for different areas of research. The one thing which would improve this would be to include the dates of these research papers, just so the reader can know how recent the work is. maybe introduce the research as Person et al (2009) has used the zebrafish to.... Also are there any pictures on this research? Just because research language is so technical, some pictures would break it up. Hope this helps you group 3.

--[[User:Z3126328|Jin Lee]] 16:06, 26 September 2009 (EST) congratulations to Group3! this is a really great assignment. overall, all the sections are well represented visually.
I liked the history part mostly! easy to read! Maybe the current research section can be improved by adding some images and relevant links. I found zebrafish is very interesting!thank you

--[[User:Z3187802|Vishnnu Shanmugam]] 19:32, 26 September 2009 (EST)Well done Zebra fish group. You've put together a well balanced assignment. The images under "Timeline and Stages of Embryonic Development" are impressive, really make the assignment stand out and the text flows nicely. I also noticed the links to researchers and research laboratories have been made throughout the text and because they are under specific headings, the reader will know what the information in the link will focus on. Additions to improve the assignment:

- there is some irrelevant images in the the text; the images "A 1981 issue of Nature journal" & "Development.jpg" are Unnecessary and could be replaced with others that support the text or summarize complex processes. (eg. motor neuron development in zebrafish or a time line showing the evolution in the use of zebrafish). The second image "Development.jpg" is better replaced with the image "A Zebrafish Pigment Mutant" as it is relevant to the text. The current research does not mension or explain the Zebrafish Pigment Mutant and thus is Unnecessary there.

- The Genetics section could do with an image of zebrafish chromosomes. This can be a simple hand drawn diagram and can be compared to the human chromosomal makeup.

- The current research section could use a description of how zebrafish research has impacted human embryology.

-The assignment needs to be properly referenced. see www.lc.unsw.edu.au/onlib/ref_apa.html for help with APA referencing.

- A Glossary would also complement the text.

Overall very impressive, only needs minor editing.

-[[User:Z3252340|Emily Wong]] 11:04, 27 September 2009 (EST) To begin with, you have done a great job group 3. It is a well researched, structured and organized page. The student contribution to the work is fairly even. The condensation of the written content is done well, with the combining of the timeline and stages in one section and extensive use of visual representation. However, information is not provided when clicking on the pictures as to what is in them. A description or explanation of what is occurring in each stage or at each time point would improve this project. Some of the images used have not been referenced properly in the image pages. Referencing is good and an extensive reference list has been provided. The content provided is very detailed by still brief and relevant to each section. This project could also be improved by adding some examples of current research and also referencing information throughout the written content. Perhaps an inclusion of a Pubmed search link in the current research section would be a good idea so that viewers can see what other research has been done using the zebrafish.

--[[User:Z3126345|Gang Liu]] 16:17, 27 September 2009 (EST)This is a very informative, well constructed and concise wikipage. It has demonstrated consistency throughout the page. There are a number of major subheadings have been included history, timeline, development, genetics and current embryology research as well as hand drawing. In addition, it has demonstrated extended research of literatures. For example, by dividing the history section in a number of subheadings such as "in the beginning", "Charles Kimmel", "Hesitations", etc. This has indicates the in-depth understanding of zebrafish embryo model use. It allows the reader to appreciate story behind the experiment, as well as scientists' thinking process and thoughts. "...there was no gene cloning and little understanding about genes, making the whole zebrafish project almost a gamble to follow through with. This put much strain on the funding given to Streisinger and the credibility of his work...".

The graphic delivery of timeline and stages are very self-explanatory and powerful. A picture explains a thousand words. It makes the section easy to follow, and interesting to read also.

However, this project can be improved by considering the following points.

*I found genetic and current embryology section were very lengthy and wordy, and lack of pictures. In addition, referencing in these two sections were inconsistent with previous sections;

*Lack of glossary list. Such as "oxidative phosphrylation", "N-ethyl-N-nitrosourea (ENU)", "Diploid" and "Haploid" need to provide meanings;

*Inconsistent referencing. Name of author need to keep in alphabetical order. Also articles and web based materials are mixed. The first five references were inconsistent with the rest in style;

Last few words. I enjoyed reading it, learned something out of it. Big thumb up for me.

--[[User:Z3217686|Thomas Dangerfield]] 13:54, 28 September 2009 (EST)Well done guys! Nice, visually stimulating assignment! Just a few points about possibly having a little more written info on the timeline, just to help explain what is in each image. Also some pictures of the chromosomes of the zebrafish would be a handy visual tool. This may just be a little picky, but i notice that you have a few heading issues:

- Beginning not Begining. (In the begining..)

- Genetics of the Zebrafish and Embryology, and the you have a 'Genetics and Embryology' a couple of headings down which seems a little unnecessary.

Just as a hint on being thorough, maybe a glossary could have been included, as well as formatting for your references. Still, a well presented assignment has been done here!

--[[User:Z3185685|Sumaiya Rahman]] 16:06, 28 September 2009 (EST) Hey guys. Well done on the assignment overall. It was interesting to read about the zebrafish. The page was well introduced. It is god that you broke up the information using subheadings. This makes the page a lot easier to read as it breaks up the big slabs of text. I think has been mentioned, but there are a couple of spelling mistakes. Also the sentence “This however did not affect Neurologists such as Kimmel as they were not much worried about the relevance of their work” needs to be fixed up. This is only a minor error. The history section could look a little bit less messy if the pictures were placed on the same side. “The fish is a frog... is a chicken... is a mouse” picture is very cute! But maybe a little bit too big because we need to scroll across to see it (or is that just me?). You have some great references and links and a great timetable and stages section with good visuals. The genetics and current research sections have a lot of text, maybe finding a way of making these sections more visually appealing would help the readers. Also including a glossary would help. Overall nice work!

----

--[[User:S8600021|Mark Hill]] 01:44, 8 September 2009 (EST) A single image of a fish, well that really gets across the message of zebrafish development, interpret the information you have read and put it into a format that will interest the reader.

ZebraFish - Zebrafish are really cool...

I'm happy with zebrafish... never heard of them but they sound interesting :) what does everyone else think? ...Gaby Pinget

Great, who else is in our group then... Oh and i'm Sal by the way

Ok so i'm not sure who the other two are because i don't know your number but just for reference my number is z3218657.
I found this cool website with some pictures of Zebrafish embryo's developing... its pretty cool...

http://www.cas.vanderbilt.edu/bioimages/animals/danrer/zfish-devel.htm

and this website shows all the stages and times and such good for a timeline

http://zfin.org/zf_info/zfbook/stages/stages.html

Research Topics for this week:
- Timeline and Staging (Sal)
- History of Model Use (Gaby)
- Genetics (Bronwyn)
- Current Embryology Research (Jo)
--> Share what we've learnt with the group next session.

Hey Guys I have a lot of info... and i don't think i should post it all up here because there is a lot of stuff... Mainly all about the Staging though. I am going to put up a summary of the different stages. The website i gave you before ZFIN is the zebrafish database of model organisms. its great!

'''Zygote Period''' – Lasts for 0-0.75hours
Transition of one cell to two cells.
Fertilisation occurs activating cytoplastimic movement. The animal poles within the cell segregate the blastodisc from the yolk cytoplasm. Segregation continues into the cleavage staging.

'''Cleavage Period''' – Lasts for 0.75-2.25 hours
Transition from two cells to 128 cells
After the first cleavage the blastocysts division is approx every 15 minutes.

'''Blastula Period''' – Lasts for 2.25-5.25 hours
Transition from 128 cells to 50% epibolby
“Epiboly, beginning in the late blastula (Solnica-Krezel and Driever, 1994), is the thinning and spreading of both the YSL and the blastodisc over the yolk cell, as you might model by pulling a knitted ski cap over your head” – Direct quote from the ZFIN website

'''Gastrula Period''' – Lasts for 5.25-10.33 hours
Transition from 50% epibolby to 1-4 somites
The gastrula period ends when epiboly is complete, and the tail bud has formed. Here each germ layer (endoderm, mesoderm, ectoderm) is put in the right place so that bodily organs and tissues can form in the correct locations.

'''Segmentation period''' – Lasts from 10.33 – 24 hours
Transistion from 1-4 somites to Prim-5
Here dermis, vertebrae and skeletal muscle are formed

'''Pharyngula Period''' – Lasts from 24 – 48 hours
Transition from Prim 5 to Long-pec
The body axis begins to straighten and the fins begin to develop.

http://www.youtube.com/watch?v=0hGT667ktTw

'''Hatching Peroid''' – Last from 48 to 72hours
Transitions from Long-Pec to Protruding-mouth
In this period, primary organ systems develop and cartilage development begins.

'''Larval Period''' – Lasts from 72hours to 30days
transition from Protruding-mouth to Day 30-44
The pectoral fin continues to develop and the internal organs become more complex. Development continues.

'''Juvenille Period''' – Lasts from 30-44 days
Here adult fins and pigments as well as 12 teeth develop.

'''AdultPeriod''' – Lasts90days to 2 years
Full Breeding Adult.

http://www.youtube.com/watch?v=5ygcu9BRXI0 - Zebrafish heart beating!

http://www.youtube.com/watch?v=TbErcmhzUSY - alcohol effects on Zebrafish embryo

Websites used
http://dev.biologists.org/cgi/content/abstract/dev.022673v1

http://www.zfic.org/classroom%20experiments/stagingindex.html

http://zfin.org/zf_info/zfbook/stages/stages.html

Hey! This is a really good site with a bunch of links relating to the different areas we have to research:
http://www.sanger.ac.uk/modelorgs/zebrafish.shtml

Hey guys.... Ive found a really good picture of the zebrafish embryo development (like the human one) but I dont know how to put it up, was thinking it might be better if it was actually on the page rather than a link to get the picture. JO

well I think that I just uploaded a picture but I have no idea where to... wow I'm so lost... Maybe that's a good thing because I have a feeling that it was copy right protected... DAMN COPY RIGHT ah ha ha

Hey all, all the websites that i have put up on this page have really good images... I have emailed the three of them and asked if it was ok if i used them to put up on here and i am awaiting a reply so
hopefully they will let us use them. Also i am having a tonne and a half of trouble uploading a InDesign Timeline image i created of the timeline and also having some issues with the net so i might
bring them to class and see if the computers there are readable other wise i am screwed and will just have to start all over again. I have a more complete Timeline and Staging format that i have
created as well. I'll put that up when i try and upload the image again. Peace. - Sal

Hey Hey So I got permission from Judy Cebra-Thomas to use all her images on her website which are each stage of development - YAY we just have to accredit them. So today apart from working on
unwinding my InDesign TImeline and putting the info up in bullets i am going to start to figure out whats happening in all the images and try an upload them onto the site so hopefully tomorrow we
will have an almost finished timeline and staging section! - Sal

Right so I've posted a link to the current sequencing status on the genetics part of our site. This updates pretty much everyday so I will be able to update ours right before submission so we have up-to-date info. This is however a minor detail so I'm writing it here to help us all remember! :) thanks

'''Hey guys!! please read this: I put up pictures which are really just to make it look pretty rather than add any info. Can you please tell me if you think they're stupid or not serious enough? I promise that I wont be offended! I understand if any of you think that we should take our assignment more seriously than that... it's just hard to find images for a history of zebrafish use!'''

I dont really get the light bulb lol. Sally were u able to get the embryo stage images as a link to the info as u wanted???? I think its a really good idea if we could do it, i think it might be a matter of asking someone who's actually good with computers to do it lol. Im still complying info for the current research section, currently in qld but i wanna have it up hopefully by this week, at least part of it anyways. Im gonna try n get some pictures but every place that ive asked think im an actual doctor lol so its been a bit hard.

Ok so not quite sure how to do the linking but i might just make it all link off the page into separate little pages... does that make sense??? Probably not but i can try explain it better on thursday. The
images take me 1.5hours each to upload because i have to make the image in indesign, Grab it and then transform the image to a PNG file as that is one that this website allows for uploading! So they
are coming up but ever so slowly! When i got permission to use the images i just told them I was a student studying Advance Science from UNSW. I was enrolled in an embryology course there where
we were doing an assignment on the Embryology of Zebrafish. Could i please use your images with referencing and a link to your webpage or document. Thats kind of what i said! i'm hoping to have it
all up and ready on thursday but might have to finish it friday night as have friends down from QLD that tend to make my place messy and have a house inspection on that ARVO!!! - Cheers SAL

Hey Sally, just so u know. I moved the websites you used to the references section so it didnt seem odd to keep it after ur info.

Hey Sally, we were thinkin about whether or not we could mix the timeline with the stages, so we thought that maybe if on the actual page we had the timeline with the pictures, then by clicking on the pictures there would be the info that u got or maybe even putting it all into a table so the pictures & info are more integrated.

Hey guys sorry i wasn't in class yesterday i had a funeral. What i was thinking of doing was actually moving all the data off the page and you click on it to go to another page which as all the info! but
the idea of clicking on the picture and going to it sounds great. One flaw is that is it ok if i use the pictures twice because i have been cutting, altering, adding text and flattening the images so that
they have a caption of what is happening. If i just cut another image to show each stage and then you click on that to go to it i think that could be cool as long as when you open the next page it still
has the information and the image with the caption of what is occurring! Hope thats ok. I will work on it all tonight and hopefully finish. Its taking a lot more time than expect sorry!Sal

hey Guys so I don't know if you guys have checked the website out yet but i have been working on it today! I continued what i was doing with the linked page and have also drawn my own diagrams
which are colour coded and easy for people to understand what is going on during the stages. I thought it looked cool. I haven't finished yet - a few more periods to go but i can't look at the screen
any more so i will do some on tuesday night! Hope thats ok. Just wondering though about the Nature article images above it kind of comes across the screen and i was wondering if we could somehow
move the image a little higher or enter down some spaces so that the timelines section is lower and the nature article doesn't come over the images pushing the table to the left! Let me know what you
all think. Sal

Hey Sal, your part of the project looks great! I really like the idea of clicking onto another page to get the info. works really really well and it's really easy to understand. As for the size of the picture obscuring your section, I think that you already thumbnailed it and it looks fine. Also, do you know how to put a youtube video onto the webpage? I was able to for a project in another class and it looked good but that was much easier because it had a link to a bunch of plug ins i could use. If anyone has any ideas please let me know! Gaby

Hey Sally, ur part looks awesome!!! Everyone done forget about your references...ive tried making the ones there so far look like it was done by one person lol. I dont know how to do the youtube clip thing but i have one too, was thinking maybe we should have a section for helpful links or do u think we should just put the links in with watever section its assiciated with. Wat do u guys think??? Jo

Hmm I was just thinking that the best thing to do was to put up the links strait after whatever they're associated with, that way they are supplimentary to what the reader is looking at rather than random extras at the end. That'll prob work best, right? Gaby

Thanks guys I've put a tonne of effort in so hope it pays off! I was going to fix up the references (cause they just have my websites without being real references) but it took me a lot longer than i thought for the images as you
can see its 5am. Nice. Yes i think linking the videos with the relevant parts is best. I have added links to videos throughout my section. Also I have made it so that when you put your mouse over the images it comes up with its own
reference/copy right info. Also when adding a link to another website its best to name the website instead of having just the web address. Its really easy if you don't know how and i can show you how to fix them up. When we get our
feedback from the other groups we can add and so forth before the project is actually marked which is really great. I think we need more info with the Genetics part but i figure bron is doing that tomorrow! Jo I really love your
sections pics and info it great and to the point!Gaby, yeah i did move it hope thats ok. I do have one question though and not meaning to hurt your feelings but i'm not that keen on the drawn image of the bird,fish,frog and mouse.
It doesn't really fit. Sorry, I mean obviously the decision is up to you, but i think it just looks a bit odd in the middle of the page because it you see it first and think , what? That was just some of the other feedback i got
from some of my friends that i asked to check out the website and see how they could maneuver around it. So that's my major spiel. Catch ya tomorrow. Sal

Talk:2009 Group Project 2

2009-09-28T05:39:53Z

Z3185685:

----

--[[User:Z3185685|Sumaiya Rahman]] 15:39, 28 September 2009 (EST) Hey Fly group! Congrats on the assignment, you guys did a great job! The introduction is well written as it gives the readers an overall image of what to expect on the page. The timetable of emryogenesis is good as it breaks up the text, however including labels in the images would help readers better understand the information given. The stages section is fantastic! The use of images in a table makes it very easy to understand. There are a few grammatical errors in the history of model use section which need to be fixed up. For example, “an American geneticist and embryologist, was looking for an inexpensive that could be breed quickly and in limited space and Castle suggested the drosophila”. Also the genetics and current embryology sections seem quite short. Maybe a little bit more content in both these sections will give the readers a better understanding. 

--[[User:Z3187802|Vishnnu Shanmugam]] 12:13, 26 September 2009 (EST)
Great work fly group. Your assignment looks visually appealing and the information presented is well summarized (still amazed that a fly can fully develop in 22 hours). A real plus point in your assignment is how you've used RELEVANT images to support the text. Now let's get to what matters. Ways to improve the assignment:

- With the timeline of Drosophila Development, try to add keys or labels to the "timetable of embryogenesis" image to distinguish the different developing structures. I't a bit hard to see what the green, red and yellow structures in the image represent.

- Under "history of embryological model use" and "genetics" you might be able to mension Gregor Mendel, his work with flies and the contribution he made to the genetics of all organisms as well as the fly.

- The genetics section needs more information maybe the inclusion of how phenotype changes can be achieved from Monohybrid cross of flies with dominant and recessive alleles. Find out more my google searching "Mendelian inheritance". This can then flow to improve the current research section on "The use of Drosophila as a model for the development of human traits".

- The current reaserch section needs some work on it. The inclusion of visual aid to support the text should help. Investigate on dominant/recessive genetic trees and how they are used in Drosophila to model inherited diseases.

- The assignment needs to be properly referenced as there is no references made in the actual text. see www.lc.unsw.edu.au/onlib/ref_apa.html for help with APA referencing.

- A Glossary would also complement the text.

Overall great job.....some additions will make it excellent!

--[[User:Z3224449|Elide Newton]] 14:26, 26 September 2009 (EST) HELLO GROUP 2: Well concrats on producing a really great assignment! I'm impressed with the staging sections and how well the visual content represents the written. Well my one comment of improvement would have to be on equal content for each section. I feel the last 2 sections ( genetics and current research) are lacking in info. I understand genetics might be difficult to get informations. For the current research section try Pubmed and type in the fly, these articles will be cutting edge. Also if you could include '''How''' they are used in current research.. eg are their genes manipulate, cross bred, transgenic etc. ie the process of how they are used ? I really hope this helps!

--[[User:Z3126328|Jin Lee]] 16:56, 26 September 2009 (EST)congratulation group 2. Well done! it's a great assignment! Here is my comments: History section needs to be referenced properly and may be some more images and relevant links as well. Information about genetics and current research are little lacking..try to add some links. I am very impressed with the images in the staging section and the way it links to more information. the assignment needs to be looked after the reference part.

--[[User:Z3254857|Begum Sonmez]] 22:37, 26 September 2009 (EST)
Hello Group 2, Congratulations on your page. I found that your page was interesting, and easy to read. No overload. Just wanted to say a few things about the History section:

*The overuse of the word ''In'' is unnecessary, and repetitive. A possible alternative would be to replce them with the DATE or the Researchers as sub-headings.

*When mentioning a researcher for the first time, refer to them with their full name whenever possible. This is relevant to the viewer as he or she may make use of the full name (they may want to 'google' the researcher for example). For example, 'Muller' or 'Morgan'.

*I found that some of the findings were expressed generally rather than making direct reference to the Drosophilia embryo. For example, instead of stating that Morgan won a nobel prize 'for his discovery that genes are carried on chromosomes and are the mechanical basis of hereditary', a brief explanation of how Morgan used your chosen animals embryo would be useful. I hope I am making sense.

*A direct link to the researcher's published article would be helpful whenever possible. This allows for quick access for an interested viewer.

For the Genetics section:

*The Genetics section was interesting, however considering the great importance of genetics, more information would widen the knowledge of the reader. It can be improved with information on transgenic Drosophilia, or drosophilia stem cells.

*After mentioning the simplicity of it's genome, you have outlined the use of the embryo to '...trial new gene expressions in its genome.' This is not a major concern for me, though the inclusion of an example would be more informative.

The current research section was very clear, relevant to the topic, interesting, and informative.

The 'Helpful Links' were relevant to the topic, and they were 'Helpful'. In particular, the FlyBase.

Last of all, a direct link to a video showing the development of the musculature or the gut would be interesting to see. But I find that it isn't crucial to have when the information is structured very well. This is more so, for the reason of the presence of a different medium.

Overall, I found that the structure of each section was clear and easy to read and understand. The sentences in each paragraph were flowing very well (in particular, the introduction). The content of the page was highly relevant. Great job Group 2, I'm impressed.

--[[User:Z3252340|Emily Wong]] 11:02, 27 September 2009 (EST) To start off, great work group 2. You've done an awesome job. It is a very concise, well structured and organized page. Each section of content appears to be well researched and referenced properly. The information is well summarized with only the relevant content included. The use of visual representations of information is good, particularly in the timeline and staging sections. Student contribution to the page is fairly evenly distributed. This project could be improved by including some more information on the content needed as it felt to me to be a little to brief.

--[[User:Z3126345|Gang Liu]] 15:40, 27 September 2009 (EST)This a well structured and self-explanatory wikipage. I had a good time reading it throughout. The cocept is easy to follow such as flies are cost effective, easy to replicate and obtain, as well as large quantities. Texts are informative, on top of that, graphics are appropriate, which also makes it interesting to read. There are a number of major subheading have been included such as hitory, timeline, stages, genetics and current embryology.

However, the following points could take into consideration to improve the page.

*Lack of information in section such as history. This section's content was very brief and lack of details and flow. For example, "In 1900, Ectomologist Charles W. Woodworth was the first to breed the Drosophila at Harvard university and suggested to W.E. Castle they could be used in studies of genetics.". This can be improved by adding details of the experiment, as well as the results.

*Lack of scientific base in genetic section. Not enough reference were provided in this section. Also, it is a bit lengthy, which makes it 'dry' and difficult to read.

*Lack of glossary. A list of unfamilier words needs to be provided to assist reader. For example, "mesodermal", "postblastodermal", "mitosis", "monostratified".

*Inapproporiate referencing. For example, "Experiments conducted by Cox et. al. have located a gene in Drosophila...". It is necessary to provide proper format for reference. Instead it can be said, "Experiments conducted by Cox who, XX, YY, from University of Q (reference) have located a gene in Drosophila...".

*Lack of imformation in current research section. Needs to provide more graphics.

*Inconsistency of project.

Last words. I am impressed by the page until stages of fly development. However, i think it will be better, if the last few sections were consistent with the beginning.

----

--[[User:S8600021|Mark Hill]] 01:42, 8 September 2009 (EST) New comments should go to the top of the page, much easier to read. Like the Rabbit group, your project lacks visual interest. Where are the images of development? You want people to find this project interesting. There is more to researching this topic than simply what you can find on Wikipedia.

Hallo group 2

Being that I have no idea who you all are, let me introduce myself, I am Mitchell.

As for our little topic, what does everyone think about what we should choose?

Personally, I think Guinea Pig and Rat will obviously have the most information available, but obviously everyone is thinking the same, so it might not be available. The others should be interesting, but it would be challenging to find much information on them.

Thoughts??

carly: http://www.google.com.au/search?q=History+of+Drosophila+Embryological+Model+Use&hl=en&client=firefox-a&channel=s&rls=org.mozilla:en-US:official&hs=WT4&sa=G&tbo=p&tbs=tl:1&num=20&ei=nUefSvP1JJf6kAXBht3PDw&oi=timeline_navigation_bar&ct=timeline-navbar&cd=1

Helpful links:
http://embryology.med.unsw.edu.au/Otheremb/Fly.htm

http://embryology.med.unsw.edu.au/Movies/fly.htm

http://people.ucalgary.ca/~browder/virtualembryo/flies.html

http://www.medicalnewstoday.com/articles/131669.php

http://biology.kenyon.edu/courses/biol114/Chap13/Chapter_13A.html

http://www.sdbonline.org/fly/atlas/00atlas.htm

http://www.sdbonline.org/fly/aimain/1aahome.htm

http://www.sdbonline.org/fly/aimain/2stages.htm

http://www.sciencemag.org/cgi/content/abstract/287/5461/2185

I have also found that the 'Biology' 3rd edition by Knox textbook is fairly amazing, at least for the stages. Could be good for some inspiration??

Juls - Timeline of Development - how long

Mitchell - Staging - are there species specific staging, what occurs when

Carly - History of Model Use - when was it first used, what embryology research

Tom - Genetics - chromosome number, sequencing

Group Effort - Current Embryology Research - research papers and findings

Tom's notes:

http://www.yale.edu/ynhti/curriculum/units/1996/5/96.05.01.x.html

http://www.accessexcellence.org/AE/AEPC/WWC/1994/genentics.php

http://books.google.com.au/books?id=CgtIr1V0zxAC&printsec=frontcover&dq=drosophila+genetics&source=gbs_similarbooks_r&cad=3#v=onepage&q=&f=false

http://www.ncbi.nlm.nih.gov/sites/entrez?Db=genomeprj&Cmd=Retrieve&list_uids=29999

http://www.ncbi.nlm.nih.gov/sites/entrez?Db=genome&Cmd=ShowDetailView&TermToSearch=10015

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2147996&tool=pmcentrez

http://en.wikipedia.org/wiki/Drosophila_melanogaster

http://www.fruitfly.org/about/pubs/rubin96.html

Fly pushing: the theory and practice of Drosophila genetics, Part 7 By Ralph J. Greenspan

http://bfgp.oxfordjournals.org/cgi/reprint/2/2/128.pdf

Some info:

The Drosophila melanogaster fly has four pairs of chromosomes: the X/Y sex cells and the autosomes 2, 3 and 4. The fourth chromosome is so small that it is usually overlooked. The comparison of the insignificant 4th chromosome to the other three pairs are shown in the image to the right.

The size of the Drosophila genome is about 165 million pairs and estimated to contain about 14000 genes. In comparison, humans have 3.4 billion base pairs with about 22500 gene sequences and yeast has about 5800 genes in 13.5 million base pairs. More than 60% of the genome appears to be functional non-protein-coding DNA involved in gene expression control.

Also a good link to a variety of info: http://ceolas.org/VL/fly/index.html

For Carly http://www.ncbi.nlm.nih.gov/pubmed/10731135?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_Discovery_RA&linkpos=4&log$=relatedarticles&logdbfrom=pubmed

----

Current medical research

Parkinson's and drosophila
http://www.ncbi.nlm.nih.gov/pubmed/19638420?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

Evolution of visual systems
http://www.ncbi.nlm.nih.gov/pubmed/19467226?ordinalpos=23&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

Alzheimers
http://www.ncbi.nlm.nih.gov/pubmed/17046662

Of Flies and Man: Drosophila as a Model for Human Complex Traits
Trudy F. C. Mackay and Robert R. H. Anholt
http://arjournals.annualreviews.org/doi/abs/10.1146/annurev.genom.7.080505.115758
PMID: 16756480

----
possible pictures
http://en.wikipedia.org/wiki/File:EyeColors.jpg

http://en.wikipedia.org/wiki/File:Drosophila.jpg

http://commons.wikimedia.org/wiki/File:Drosophila_melanogaster_-_side_(aka).jpg

Hey guys,
Everything you have needs to be on the page by the end of session break because we need to focus on presentation and current research in the last two weeks.

tom: image.......
http://commons.wikimedia.org/wiki/File:Sexlinked_inheritance_white.jpg
http://commons.wikimedia.org/wiki/File:Drosophila_chromosomes.png

carly image

http://commons.wikimedia.org/wiki/File:Thomas_Hunt_Morgan.jpg

Talk:2009 Group Project 2

2009-09-28T05:39:19Z

Z3185685:

--[[User:Z3185685|Sumaiya Rahman]] 15:39, 28 September 2009 (EST) Hey Fly group! Congrats on the assignment, you guys did a great job! The introduction is well written as it gives the readers an overall image of what to expect on the page. The timetable of emryogenesis is good as it breaks up the text, however including labels in the images would help readers better understand the information given. The stages section is fantastic! The use of images in a table makes it very easy to understand. There are a few grammatical errors in the history of model use section which need to be fixed up. For example, “an American geneticist and embryologist, was looking for an inexpensive that could be breed quickly and in limited space and Castle suggested the drosophila”. Also the genetics and current embryology sections seem quite short. Maybe a little bit more content in both these sections will give the readers a better understanding. 

----

--[[User:Z3187802|Vishnnu Shanmugam]] 12:13, 26 September 2009 (EST)
Great work fly group. Your assignment looks visually appealing and the information presented is well summarized (still amazed that a fly can fully develop in 22 hours). A real plus point in your assignment is how you've used RELEVANT images to support the text. Now let's get to what matters. Ways to improve the assignment:

- With the timeline of Drosophila Development, try to add keys or labels to the "timetable of embryogenesis" image to distinguish the different developing structures. I't a bit hard to see what the green, red and yellow structures in the image represent.

- Under "history of embryological model use" and "genetics" you might be able to mension Gregor Mendel, his work with flies and the contribution he made to the genetics of all organisms as well as the fly.

- The genetics section needs more information maybe the inclusion of how phenotype changes can be achieved from Monohybrid cross of flies with dominant and recessive alleles. Find out more my google searching "Mendelian inheritance". This can then flow to improve the current research section on "The use of Drosophila as a model for the development of human traits".

- The current reaserch section needs some work on it. The inclusion of visual aid to support the text should help. Investigate on dominant/recessive genetic trees and how they are used in Drosophila to model inherited diseases.

- The assignment needs to be properly referenced as there is no references made in the actual text. see www.lc.unsw.edu.au/onlib/ref_apa.html for help with APA referencing.

- A Glossary would also complement the text.

Overall great job.....some additions will make it excellent!

--[[User:Z3224449|Elide Newton]] 14:26, 26 September 2009 (EST) HELLO GROUP 2: Well concrats on producing a really great assignment! I'm impressed with the staging sections and how well the visual content represents the written. Well my one comment of improvement would have to be on equal content for each section. I feel the last 2 sections ( genetics and current research) are lacking in info. I understand genetics might be difficult to get informations. For the current research section try Pubmed and type in the fly, these articles will be cutting edge. Also if you could include '''How''' they are used in current research.. eg are their genes manipulate, cross bred, transgenic etc. ie the process of how they are used ? I really hope this helps!

--[[User:Z3126328|Jin Lee]] 16:56, 26 September 2009 (EST)congratulation group 2. Well done! it's a great assignment! Here is my comments: History section needs to be referenced properly and may be some more images and relevant links as well. Information about genetics and current research are little lacking..try to add some links. I am very impressed with the images in the staging section and the way it links to more information. the assignment needs to be looked after the reference part.

--[[User:Z3254857|Begum Sonmez]] 22:37, 26 September 2009 (EST)
Hello Group 2, Congratulations on your page. I found that your page was interesting, and easy to read. No overload. Just wanted to say a few things about the History section:

*The overuse of the word ''In'' is unnecessary, and repetitive. A possible alternative would be to replce them with the DATE or the Researchers as sub-headings.

*When mentioning a researcher for the first time, refer to them with their full name whenever possible. This is relevant to the viewer as he or she may make use of the full name (they may want to 'google' the researcher for example). For example, 'Muller' or 'Morgan'.

*I found that some of the findings were expressed generally rather than making direct reference to the Drosophilia embryo. For example, instead of stating that Morgan won a nobel prize 'for his discovery that genes are carried on chromosomes and are the mechanical basis of hereditary', a brief explanation of how Morgan used your chosen animals embryo would be useful. I hope I am making sense.

*A direct link to the researcher's published article would be helpful whenever possible. This allows for quick access for an interested viewer.

For the Genetics section:

*The Genetics section was interesting, however considering the great importance of genetics, more information would widen the knowledge of the reader. It can be improved with information on transgenic Drosophilia, or drosophilia stem cells.

*After mentioning the simplicity of it's genome, you have outlined the use of the embryo to '...trial new gene expressions in its genome.' This is not a major concern for me, though the inclusion of an example would be more informative.

The current research section was very clear, relevant to the topic, interesting, and informative.

The 'Helpful Links' were relevant to the topic, and they were 'Helpful'. In particular, the FlyBase.

Last of all, a direct link to a video showing the development of the musculature or the gut would be interesting to see. But I find that it isn't crucial to have when the information is structured very well. This is more so, for the reason of the presence of a different medium.

Overall, I found that the structure of each section was clear and easy to read and understand. The sentences in each paragraph were flowing very well (in particular, the introduction). The content of the page was highly relevant. Great job Group 2, I'm impressed.

--[[User:Z3252340|Emily Wong]] 11:02, 27 September 2009 (EST) To start off, great work group 2. You've done an awesome job. It is a very concise, well structured and organized page. Each section of content appears to be well researched and referenced properly. The information is well summarized with only the relevant content included. The use of visual representations of information is good, particularly in the timeline and staging sections. Student contribution to the page is fairly evenly distributed. This project could be improved by including some more information on the content needed as it felt to me to be a little to brief.

--[[User:Z3126345|Gang Liu]] 15:40, 27 September 2009 (EST)This a well structured and self-explanatory wikipage. I had a good time reading it throughout. The cocept is easy to follow such as flies are cost effective, easy to replicate and obtain, as well as large quantities. Texts are informative, on top of that, graphics are appropriate, which also makes it interesting to read. There are a number of major subheading have been included such as hitory, timeline, stages, genetics and current embryology.

However, the following points could take into consideration to improve the page.

*Lack of information in section such as history. This section's content was very brief and lack of details and flow. For example, "In 1900, Ectomologist Charles W. Woodworth was the first to breed the Drosophila at Harvard university and suggested to W.E. Castle they could be used in studies of genetics.". This can be improved by adding details of the experiment, as well as the results.

*Lack of scientific base in genetic section. Not enough reference were provided in this section. Also, it is a bit lengthy, which makes it 'dry' and difficult to read.

*Lack of glossary. A list of unfamilier words needs to be provided to assist reader. For example, "mesodermal", "postblastodermal", "mitosis", "monostratified".

*Inapproporiate referencing. For example, "Experiments conducted by Cox et. al. have located a gene in Drosophila...". It is necessary to provide proper format for reference. Instead it can be said, "Experiments conducted by Cox who, XX, YY, from University of Q (reference) have located a gene in Drosophila...".

*Lack of imformation in current research section. Needs to provide more graphics.

*Inconsistency of project.

Last words. I am impressed by the page until stages of fly development. However, i think it will be better, if the last few sections were consistent with the beginning.

----

--[[User:S8600021|Mark Hill]] 01:42, 8 September 2009 (EST) New comments should go to the top of the page, much easier to read. Like the Rabbit group, your project lacks visual interest. Where are the images of development? You want people to find this project interesting. There is more to researching this topic than simply what you can find on Wikipedia.

Hallo group 2

Being that I have no idea who you all are, let me introduce myself, I am Mitchell.

As for our little topic, what does everyone think about what we should choose?

Personally, I think Guinea Pig and Rat will obviously have the most information available, but obviously everyone is thinking the same, so it might not be available. The others should be interesting, but it would be challenging to find much information on them.

Thoughts??

carly: http://www.google.com.au/search?q=History+of+Drosophila+Embryological+Model+Use&hl=en&client=firefox-a&channel=s&rls=org.mozilla:en-US:official&hs=WT4&sa=G&tbo=p&tbs=tl:1&num=20&ei=nUefSvP1JJf6kAXBht3PDw&oi=timeline_navigation_bar&ct=timeline-navbar&cd=1

Helpful links:
http://embryology.med.unsw.edu.au/Otheremb/Fly.htm

http://embryology.med.unsw.edu.au/Movies/fly.htm

http://people.ucalgary.ca/~browder/virtualembryo/flies.html

http://www.medicalnewstoday.com/articles/131669.php

http://biology.kenyon.edu/courses/biol114/Chap13/Chapter_13A.html

http://www.sdbonline.org/fly/atlas/00atlas.htm

http://www.sdbonline.org/fly/aimain/1aahome.htm

http://www.sdbonline.org/fly/aimain/2stages.htm

http://www.sciencemag.org/cgi/content/abstract/287/5461/2185

I have also found that the 'Biology' 3rd edition by Knox textbook is fairly amazing, at least for the stages. Could be good for some inspiration??

Juls - Timeline of Development - how long

Mitchell - Staging - are there species specific staging, what occurs when

Carly - History of Model Use - when was it first used, what embryology research

Tom - Genetics - chromosome number, sequencing

Group Effort - Current Embryology Research - research papers and findings

Tom's notes:

http://www.yale.edu/ynhti/curriculum/units/1996/5/96.05.01.x.html

http://www.accessexcellence.org/AE/AEPC/WWC/1994/genentics.php

http://books.google.com.au/books?id=CgtIr1V0zxAC&printsec=frontcover&dq=drosophila+genetics&source=gbs_similarbooks_r&cad=3#v=onepage&q=&f=false

http://www.ncbi.nlm.nih.gov/sites/entrez?Db=genomeprj&Cmd=Retrieve&list_uids=29999

http://www.ncbi.nlm.nih.gov/sites/entrez?Db=genome&Cmd=ShowDetailView&TermToSearch=10015

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2147996&tool=pmcentrez

http://en.wikipedia.org/wiki/Drosophila_melanogaster

http://www.fruitfly.org/about/pubs/rubin96.html

Fly pushing: the theory and practice of Drosophila genetics, Part 7 By Ralph J. Greenspan

http://bfgp.oxfordjournals.org/cgi/reprint/2/2/128.pdf

Some info:

The Drosophila melanogaster fly has four pairs of chromosomes: the X/Y sex cells and the autosomes 2, 3 and 4. The fourth chromosome is so small that it is usually overlooked. The comparison of the insignificant 4th chromosome to the other three pairs are shown in the image to the right.

The size of the Drosophila genome is about 165 million pairs and estimated to contain about 14000 genes. In comparison, humans have 3.4 billion base pairs with about 22500 gene sequences and yeast has about 5800 genes in 13.5 million base pairs. More than 60% of the genome appears to be functional non-protein-coding DNA involved in gene expression control.

Also a good link to a variety of info: http://ceolas.org/VL/fly/index.html

For Carly http://www.ncbi.nlm.nih.gov/pubmed/10731135?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_Discovery_RA&linkpos=4&log$=relatedarticles&logdbfrom=pubmed

----

Current medical research

Parkinson's and drosophila
http://www.ncbi.nlm.nih.gov/pubmed/19638420?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

Evolution of visual systems
http://www.ncbi.nlm.nih.gov/pubmed/19467226?ordinalpos=23&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

Alzheimers
http://www.ncbi.nlm.nih.gov/pubmed/17046662

Of Flies and Man: Drosophila as a Model for Human Complex Traits
Trudy F. C. Mackay and Robert R. H. Anholt
http://arjournals.annualreviews.org/doi/abs/10.1146/annurev.genom.7.080505.115758
PMID: 16756480

----
possible pictures
http://en.wikipedia.org/wiki/File:EyeColors.jpg

http://en.wikipedia.org/wiki/File:Drosophila.jpg

http://commons.wikimedia.org/wiki/File:Drosophila_melanogaster_-_side_(aka).jpg

Hey guys,
Everything you have needs to be on the page by the end of session break because we need to focus on presentation and current research in the last two weeks.

tom: image.......
http://commons.wikimedia.org/wiki/File:Sexlinked_inheritance_white.jpg
http://commons.wikimedia.org/wiki/File:Drosophila_chromosomes.png

carly image

http://commons.wikimedia.org/wiki/File:Thomas_Hunt_Morgan.jpg