2009 Group Project 1: Difference between revisions

From Embryology
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*Extremely variable to responses to general anesthetics
*Extremely variable to responses to general anesthetics


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


*1672- de Graaf found the Graffian follicle.
*1672- de Graaf found the Graffian follicle.
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*1941- Dr. Pincus succeeded in keeping rabbit embryos developing in the test  
*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
*1968- Edwards and Gardner successfully performed the first known embryo biopsy on rabbit embryos


=== Regnier de Graaf (1641–1673) ===
=== Regnier de Graaf (1641–1673) ===
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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. But Leeuwenhoek argued that the structures now known as Graafian follicles could not be eggs, but Haller suggested that the egg might be formed by the coagulation  of the fluid in 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.
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. But Leeuwenhoek argued that the structures now known as Graafian follicles could not be eggs, but Haller suggested that the egg might be formed by the coagulation  of the fluid in 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.


=== Walter Heape (1855-1928) ===
=== Walter Heape (1855-1928) ===

Revision as of 02:29, 23 September 2009

THE RABBIT (ORYCTOLAGUS CUNICULUS)

Isidro Martinez.jpg

Introduction

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.

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.


Timeline of Embryo Development

The following is a timeline 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.


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


Sizes.JPG

Staging

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

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)

Regnier de Graaf.jpg

discoveries in ovary

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. But Leeuwenhoek argued that the structures now known as Graafian follicles could not be eggs, but Haller suggested that the egg might be formed by the coagulation of the fluid in 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.


Walter Heape (1855-1928)

About 100 years ago, on 27 April 1890, Walter Heape transferred rabbit embryos from one mother to another. One animal became pregnant and delivered young from the transferred embryos. Thus the first mammalian embryo transfer experiment was successfully completed. His embryo transfer work in perspective as it relates to other contributions of this pioneer in reproductive biology.(21)

what has he done? first case of embryo transfer experiments

In 1891, Walter Heape (1855-1929), a professor and physician at the University of Cambridge, England, who had been conducting research on reproduction in numerous animal species, reported the first known case of embryo transplantation. 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.

As a result of this work, many scientists became interested in culturing eggs and embryos in the laboratory. Gregory Pincus and colleagues were the first to show how eggs of various animals would undergo maturation if released from their follicle and cultured in a laboratory.


Lymphatic System

A few years later Walter's successful embryo transfer, FT Lewis made public a short account of the development of the lymphatic system in rabbit embryos. His results are of great interest because they represent a new conception of the genesis of the lymphatics, being neither identical with the centrifugal growth theory of Sabin nor with the theory of their direct mesenchymal origin, but in a sense standing between these two.


Dr.Pincus (1903-1967)

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


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.

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) Rabbit Genome Project

WGS sequencing.gif

Genome

The Rabbit genome was published by two groups (9)

  1. 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
  2. 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: Rabbit Genome from the Nucleotide Data Bank

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 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 male rabbit with no chromosomal abnormalities. (19)

Drawn chromosome.jpg


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).


Karyotypehuman.gif










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 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.



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.



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.(1,2)


CSF accumulation in ventricles of brain increasing intracranial pressure. The pressure from the expanding ventricles force the brain and skull to grow outwards abnormally.

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. 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. It is generally acknowledged that children with hydrocephalus have mental retardation, often to the degree of being “vegetative”.


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. 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. 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.


Young rabbit with hydrocephalus caused by Vitamin A deficiency. Note the abnormally shaped cranium inflamed in appearance.



Spina Bifida

In Australia, the risk of spina bifida is two in every 1000 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.

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.

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.


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.

Spina Bifida Myelomeningocele is the most severe form of spinabifida where the actual spinal cord also protrudes out with the meninges as a cyst filled with CSF.


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

In Spina Bifida Occulta, the outer part of some of the vertebrae are not completely closed but the spinal cord and meninges are undamaged.


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. There is much Spina bifida research using rabbit model to test effective methods of correcting spina bifida. The occurance of natural spinal bifida in rabbits is rare and for experimental purposes it can be surgically created in rabbit fetuses during gestation. 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

Rabbit newborn with Spina Bifida. Note the unfused, divided vertebrae and exposed spinal cord.



Brachydactylia & Acheiropodia

Signs of Brachydactylia and Acheiropodia in rabbit, note the malformed limbs


Brachydactylia and Acheiropodia are genetic disorders characterized by skeletal malformation of the hands and feet. In Brachydactylia, the malformations commonly involve abnormal shortening of fingers and toes due poorly formed or absent bones. 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.


CT Scan of rabbit limbs showing Brachydactylia and Acheiropodia

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. Brachydactylia and Acheiropodia are autosomal recessive disorders which mean 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. 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.


x ray of rabbit limbs showing malformed bones due to Brachydactylia and Acheiropodia



Cleft lip & Cleft palate

Summary of different types of cleft palate & cleft lip


Cleft lip and palate affects one in 700 newborns in Australia. Cleft palate (palatoschisis) and cleft lip (cheiloschisis) are the terms used to describe the non-fusion of the upper lip, hard or soft palate typically occurring during the gestation phase of embryonic development. Cleft lip and cleft palate may occur individually (25% of cases) or together (50% of cases). The human embryo begins forming lips at about 6th week of pregnancy and forms the palate during the 7th to 12th week of pregnancy which normally fully fuse before birth. However, factors (both environmental and genetic) may cause the tissue forming the roof of the mouth and upper lip to not join properly resulting in cleft lip and/or palate. Thus, exploration of this phenomenon in search of preventative and corrective medicine can use the rabbit model.

Oral cavity of rabbit showing location of cleft palate



Cleft lip and palate can be induced in rabbit embryo by administering glucocorticoids to pregnant dams during mid gestation. The developing secondary palate has glucocorticoid receptors, the administration of glucocorticoids increases the number and sensitivity of the glucocorticoid receptors. The increased glucocorticoid receptors inhibit collagen synthesis and growth of palate leading to inhibition of closure of embryonic secondary palate. With the improperly fused palate, there is an increased likelihood of improperly fused lip resulting in cleft lip as well. Cleft lip and palate induced in rabbit embryos can be used to test effective correction techniques.





Current Embryology Research

References

  1. Dr Mark Hill 2009, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G [6]
  2. E.Horne Craigie, University of Toronto Press 1948, Bensley's Practical Anatomy of the Rabbit 8th Edition
  3. 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.
  4. 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.
  5. Jay, V. (2000). "A portrait in history. The legacy of Reinier de Graaf". Archives of Pathology & Laboratory Medicine 124(8): 1115–6.
  6. Lois N Magner. "A history of the Life Sciences" 3rd edition
  7. 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
  8. National Center for Biotechnology Information. (June 16, 2009). Rabbit Genome Resources, Retrieved August 20, 2009, from NCBI Rabbit Genome Site
  9. The Broad Institute. (2008). Rabbit Genome Sequencing Project. Retrieved only August 29, 2009, from Rabbit Genome Sequencing Project
  10. Campbell, M. A. (2002). Sequencing Whole Genomes: Hierarchical Shotgun Sequencing v. Shotgun Sequencing Retrieved August 31, 2009, from Shotgun Sequencing - 1
  11. Trivedi, B. (2000). Sequencing the Genome. Retrieved September 4, 2009, from Shotgun Sequencing - 2
  12. 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 Rabbit Genome & its Immunological Interest
  13. Ensembl (2009). Rabbit (Oryctolagus cuniculus). Retrieved September 5, 2009, from Ensembl Genome Project
  14. 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 Complete homology maps of the rabbit Article "PMID 10575232"
  15. Brunner, R., Knopp, A., Rudolph, W. (n.d). Rabbit chromosome analysis by image processing. Journal of Applied Rabbit Research.
  16. DebMark Rabbit Education Resource (2006). Rabbit Genetics. Retrieved September 6, 2009, from Rabbit Genetics
  17. Painter, T. (2009) Studies in mammalian spermatogenesis VI. The chromosomes of the rabbit. Journal of Morphology. 43(1): 1-43.
  18. Hofsaess, F., and Meacham, T. ( 1995) Chromosome abnormalities of early rabbit embryos. Journal of Experimental Zoology. 177 (1): 9-11 Chromosome abnormalities
  19. 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.
  20. Patil, M. et al (2004) Chromosome analysis of domestic rabbit. The Journal of Bombay Veterinary College. 12 (1 and 2)
  21. 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)


hydrocephalus


1) http://www.brainaustralia.org.au/AZ_of_Brain_Disorders/hydrocephalus

2) http://www.ninds.nih.gov/disorders/hydrocephalus/detail_hydrocephalus.htm

3) Developmental Medicine & Child Neurology 1999, 41: 364–374. Roger Lewin, "Is Your Brain Really Necessary?" Science 210 December 1980, p. 1232

4) Silicone oil-induced hydrocephalus in the rabbit

Marc R. Del Bigio 1, and J. Edward Bruni 2

1 Department of Pathology and 2 Department of Anatomy, University of Manitoba, Winnipeg, Manitoba, Canada Received July 13, 1990 Child's Nerv Syst (1991) 7:79-84

5) A case of hydrocephalus and MENINGOENCEPHALOCELE IN A RABBIT,CAUSED BY AQUEDUCTAL MALFORMATION by J. A. G. GEELEN Psychopathological and Neurophysiological Laboratory, Department of Neurology, University of Nijmegen, The Netherlands

Laboratory Animals (1974) 8, 167-176.

6) Hydrocephalus in Young Rabbits Associated with Maternal Vitamin A DeficiencyBY G. E. LAMMINGX A.R.C. Unit of Animal Reproduction, Huntingdon Road, Cambridge AND D. H. M. WOOLLAM AND J. W. MILLEN Department of Anatomy, University of Cambridge British Journal of Nutrition, Vol. 8, No. 4


Spina Bifida

1) http://www.spinabifida.asn.au/

2) http://www.betterhealth.vic.gov.au/bhcv2/bhcarticles.nsf/pages/Spina_bifida_explained

3) Dr Mark Hill UNSW CRICOS Provider Code No. 00098G

4) Neurulation in the rabbit embryo Marian C.E. Peeters • Christoph Viebahn Johan W.M. Hekking • Henny W.M. van Straaten Anat Embryol (1998) 197:167–175

5) Review of Animal Models of Surgically Induced Spinal Neural Tube Defects: Implications for fetal surgery

                     Timothy M. George; Eric Fuh
                    Pediatric Neurosurgery; Aug 2003; 39, 2; Academic Research Librarypg. 81

6) A Different Technique to Create a 'Myelomeningocele-Like' Defect in the Fetal rabbit Denise A.L. Pedreira; Paulo R. Valente; Rogério C. Abou-Jamra; Cláudio L. Pelarigo Fetal Diagnosis and Therapy; Nov/Dec 2002; 17, 6; Academic Research Library pg. 372

7) EMBRYOLOGICAL STAGES IN THE ESTABLISHING OF' MYELOSCHISIS WITH SPINA RIFIDA BRADLEY M. PATTEN Uepartnient of Anatomy, University of Michigan Xadicul Schoot, Ann Arbor AMERICAN JOURNAL OF ANATOMY 93 (3): 365-395 1953

8) Successful Fetal Surgery for the Repair of a 'Myelomeningocele-Like' Defect Created in the fetal rabbit Denise A.L. Pedreira; Paulo R. Valente; Rogério C. Abou-Jamra; Cláudio L. Pelarigo Fetal Diagnosis and Therapy; May/Jun 2003; 18, 3; Academic Research Library pg. 201


Brachydactylia & Acheiropodia

1)Osteoscintigraphy and brachydactylia of the hand Myron L. Lecklitner and Kelley P. Douglas Department of Radiology, University of South Alabama, Mobile, Alabama, USA Eur J Nucl Med (1986) 12:436-437

2)HEREDITARY BRACHYI)ACTYLIA AND ALLIED ABNORMALITIES IN THE RABBIT BY HARRY S. N. GREENE, M.D., AND JOHN A. SAXTON, JR., M.D. (From tke Department of Animal and Plant Patkology of Tke Rockefeller Institute for Medical Researck, Princeton, New Yersey) THE JOURNAL OF EXPERIMENTAL MEDICINE VOL. 69

3)Acheiropodia is caused by a genomic deletion in C7orf2, the human orthologue of the Lmbr1 gene 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

4) Brachydaetylia with Symphalangism, Probably Autosomal Recessive Roland ~Valbaum, Claude Hazard, and Roger Cordier Centre Hospitalier, Roubaix, France Hum. Genet. 33, 189--192 (1976)

5) Osteoscintigraphy and brachydactylia of the hand Myron L. Lecklitner and Kelley P. Douglas Department of Radiology, University of South Alabama, Mobile, Alabama, USA Eur J Nucl Med (1986) 12:436-437


cleft lip & palate

1) http://www.chw.edu.au/parents/factsheets/cleftlpj.htm

2) http://www.betterhealth.vic.gov.au/bhcv2/bhcarticles.nsf/pages/Cleft_palate_and_cleft_lip

3) http://www.chw.edu.au/parents/factsheets/cleftlpj.htm

4) Epidemiology of congenital clefts of the lip and palate JOHN C. GREENE D.M.D. ,M.P.H. Public Health Rep. 1963 July; 78(7): 589–602

5) Cleft palate induction in hamster fetuses by glucocorticoid hormones and their synthetic analogues By RAVINDRA M. SHAH1 AND ALAN KILISTOFF From the Department of Oral Biology, Faculty of Dentistry, University of British Columbia, Canada Embryol. exp. Morph. Vol. 36, l,pp. 101-108, 1976










ANAT2341 group projects

Project 1 - Rabbit | Project 2 - Fly | Project 3 - Zebrafish | Group Project 4 - Mouse | Project 5 - Frog | Students Page | Animal Development File:Example.jpg