Mouse Knockout: Difference between revisions

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Embryology - 18 Apr 2024 Expand to Translate
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Introduction

The mouse (taxon-mus) has always been a good embryological model, generating easily (litters 8-20) and quickly (21d). Mouse embryology really expanded when molecular biologists used mice for gene knockouts. The term "knockout mouse" is a mouse where researchers have inactivated, or "knocked out," an existing gene by replacing it or disrupting it with an artificial piece of DNA. Currently there is a scientific drive to establish a knockout for all known mouse genes, and new technologies allow both "conditional knockouts" and "knockins".

Now it is necessary to understand development, in order to understand the effect of knocking out these gene.

--Mark Hill (talk) 08:35, 24 June 2014 (EST) Note the external links below no longer function. The database has been relocated. I will remove this notice when links are repaired.

External Links Notice - The dynamic nature of the internet may mean that some of these listed links may no longer function. If the link no longer works search the web with the link text or name. Links to any external commercial sites are provided for information purposes only and should never be considered an endorsement. UNSW Embryology is provided as an educational resource with no clinical information or commercial affiliation.

mouse | Molecular Development - Genetics

Mouse Stages: E1 | E2.5 | E3.0 | E3.5 | E4.5 | E5.0 | E5.5 | E6.0 | E7.0 | E7.5 | E8.0 | E8.5 | E9.0 | E9.5 | E10 | E10.5 | E11 | E11.5 | E12 | E12.5 | E13 | E13.5 | E14 | E14.5 | E15 | E15.5 | E16 | E16.5 | E17 | E17.5 | E18 | E18.5 | E19 | E20 | Timeline | About timed pregnancy

Species Embryonic Comparison Timeline

Carnegie

Stage

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

21

22

23

Human

Days

1

2-3

4-5

5-6

20

22

24

28

30

33

36

40

42

44

48

52

54

55

58

Mouse

Days

1

2

3

E10

E11

E12

E13

E14

E15

E16

Rat

Days

1

3.5

4-5

5

6

7.5

8.5

9

10.5

11

11.5

12

12.5

13

13.5

14

14.5

15

15.5

16

16.5

17

17.5

Note these Carnegie stages are only approximate day timings for average of embryos. Links: Carnegie Stage Comparison

Table References
Human O'Rahilly R. (1979). Early human development and the chief sources of information on staged human embryos. Eur. J. Obstet. Gynecol. Reprod. Biol. , 9, 273-80. PMID: 400868 Otis EM and Brent R. Equivalent ages in mouse and human embryos. (1954) Anat Rec. 120(1):33-63. PMID 13207763 Mouse Theiler K. The House Mouse: Atlas of Mouse Development (1972, 1989) Springer-Verlag, NY. Online OTIS EM & BRENT R. (1954). Equivalent ages in mouse and human embryos. Anat. Rec. , 120, 33-63. PMID: 13207763 Rat Witschi E. Rat Development. In: Growth Including Reproduction and Morphological Development. (1962) Altman PL. and Dittmer DS. ed. Fed. Am. Soc. Exp. Biol., Washington DC, pp. 304-314. Pérez-Cano FJ, Franch À, Castellote C & Castell M. (2012). The suckling rat as a model for immunonutrition studies in early life. Clin. Dev. Immunol. , 2012, 537310. PMID: 22899949 DOI.

Some Recent Findings

Mouse E14.5 from transcriptome atlas^[1]

Restoration of Spermatogenesis and Male Fertility Using an Androgen Receptor Transgene^[2] "Androgens signal through the androgen receptor (AR) to regulate male secondary sexual characteristics, reproductive tract development, prostate function, sperm production, bone and muscle mass as well as body hair growth among other functions. We developed a transgenic mouse model in which endogenous AR expression was replaced by a functionally modified AR transgene. A bacterial artificial chromosome (BAC) was constructed containing all AR exons and introns plus 40 kb each of 5' and 3' regulatory sequence. Insertion of an internal ribosome entry site and the EGFP gene 3' to AR allowed co-expression of AR and EGFP. Pronuclear injection of the BAC resulted in six founder mice that displayed EGFP production in appropriate AR expressing tissues. The six founder mice were mated into a Sertoli cell specific AR knockout (SCARKO) background in which spermatogenesis is blocked at the meiosis stage of germ cell development. The AR-EGFP transgene was expressed in a cyclical manner similar to that of endogenous AR in Sertoli cells and fertility was restored as offspring were produced in the absence of Sertoli cell AR. Thus, the AR-EGFP transgene under the control of AR regulatory elements is capable of rescuing AR function in a cell selective, AR-null background. These initial studies provide proof of principle that a strategy employing the AR-EGFP transgene can be used to understand AR functions."
Mouse library set to be knockout^[3] "Launched in 2006 in North America and Europe, the effort aims to disable each of the 20,000-odd genes in the mouse genome and make the resulting cell lines available to the scientific community."
A conditional knockout resource for the genome-wide study of mouse gene function^[4] "Gene targeting in embryonic stem cells has become the principal technology for manipulation of the mouse genome, offering unrivalled accuracy in allele design and access to conditional mutagenesis. To bring these advantages to the wider research community, large-scale mouse knockout programmes are producing a permanent resource of targeted mutations in all protein-coding genes. Here we report the establishment of a high-throughput gene-targeting pipeline for the generation of reporter-tagged, conditional alleles. Computational allele design, 96-well modular vector construction and high-efficiency gene-targeting strategies have been combined to mutate genes on an unprecedented scale. So far, more than 12,000 vectors and 9,000 conditional targeted alleles have been produced in highly germline-competent C57BL/6N embryonic stem cells. High-throughput genome engineering highlighted by this study is broadly applicable to rat and human stem cells and provides a foundation for future genome-wide efforts aimed at deciphering the function of all genes encoded by the mammalian genome."

More recent papers
This table allows an automated computer search of the external PubMed database using the listed "Search term" text link. This search now requires a manual link as the original PubMed extension has been disabled. The displayed list of references do not reflect any editorial selection of material based on content or relevance. References also appear on this list based upon the date of the actual page viewing. References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability. More? References \| Discussion Page \| Journal Searches \| 2019 References \| 2020 References Search term: Knockout Mouse <pubmed limit=5>Knockout Mouse</pubmed>

Mouse Gene Knockouts Listed according to the Name of the Gene

List from bioscience.org mouse gene knockouts http://www.bioscience.org/knockout/alphabet.htm

A

B

C

D

E

Jnk3

Oxytocin

WT-1

XPA
XPC

External Links

External Links Notice - The dynamic nature of the internet may mean that some of these listed links may no longer function. If the link no longer works search the web with the link text or name. Links to any external commercial sites are provided for information purposes only and should never be considered an endorsement. UNSW Embryology is provided as an educational resource with no clinical information or commercial affiliation.

International Knockout Mouse Consortium (IKMC) The International Knockout Mouse Consortium (IKMC) aims to mutate all protein-coding genes in the mouse using gene trapping and gene targeting in C57BL/6 ES cells.
NIH - The Knockout Mouse Project (KOMP) Is a trans-National Institutes of Health (NIH) initiative that aims to generate a comprehensive and public

KOMP The University of California, Davis (UC Davis) and Children's Hospital Oakland Research Institute (CHORI) will collaborate to preserve, protect and make available knockout mice and related products available to the research community. The repository will archive, maintain and distribute up to 8,500 strains of embryonic stem cell clones, live mouse lines, frozen embryos and sperm and vectors.

Historic Embryology
1897 Pig \| 1900 Chicken \| 1901 Lungfish \| 1904 Sand Lizard \| 1905 Rabbit \| 1906 Deer \| 1907 Tarsiers \| 1908 Human \| 1909 Northern Lapwing \| 1909 South American and African Lungfish \| 1910 Salamander \| 1951 Frog \| Embryology History \| Historic Disclaimer

Glossary Links

Glossary: A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z | Numbers | Symbols | Term Link

Cite this page: Hill, M.A. (2024, April 18) Embryology Mouse Knockout. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Mouse_Knockout

What Links Here?

↑ <pubmed>21267068</pubmed>| PLoS Biol. | Eurexpress transcriptome atlas
↑ <pubmed>25803277</pubmed>
↑ <pubmed>21677718</pubmed>| Nature News
↑ <pubmed>21677750</pubmed>

[PMID21267068-1] <pubmed>21267068</pubmed>| PLoS Biol. | Eurexpress transcriptome atlas

[PMID25803277-2] <pubmed>25803277</pubmed>

[3] <pubmed>21677718</pubmed>| Nature News

[PMID21677750-4] <pubmed>21677750</pubmed>

[1]

[2]

[3]

[4]

@@ Line 23: / Line 23: @@
 |-bgcolor="F5FAFF"
 |
+* '''Restoration of Spermatogenesis and Male Fertility Using an Androgen Receptor Transgene'''<ref name="PMID25803277"><pubmed>25803277</pubmed></ref> "Androgens signal through the androgen receptor (AR) to regulate male secondary sexual characteristics, reproductive tract development, prostate function, sperm production, bone and muscle mass as well as body hair growth among other functions. We developed a transgenic mouse model in which endogenous AR expression was replaced by a functionally modified AR transgene. A bacterial artificial chromosome (BAC) was constructed containing all AR exons and introns plus 40 kb each of 5' and 3' regulatory sequence. Insertion of an internal ribosome entry site and the EGFP gene 3' to AR allowed co-expression of AR and EGFP. Pronuclear injection of the BAC resulted in six founder mice that displayed EGFP production in appropriate AR expressing tissues. The six founder mice were mated into a Sertoli cell specific AR knockout (SCARKO) background in which spermatogenesis is blocked at the meiosis stage of germ cell development. The AR-EGFP transgene was expressed in a cyclical manner similar to that of endogenous AR in Sertoli cells and fertility was restored as offspring were produced in the absence of Sertoli cell AR. Thus, the AR-EGFP transgene under the control of AR regulatory elements is capable of rescuing AR function in a cell selective, AR-null background. These initial studies provide proof of principle that a strategy employing the AR-EGFP transgene can be used to understand AR functions."
 * '''Mouse library set to be knockout'''<ref><pubmed>21677718</pubmed>| [http://www.nature.com/news/2011/110615/full/474262a.html Nature News]</ref> "Launched in 2006 in North America and Europe, the effort aims to disable each of the 20,000-odd genes in the mouse genome and make the resulting cell lines available to the scientific community."
 * '''A conditional knockout resource for the genome-wide study of mouse gene function'''<ref name="PMID21677750"><pubmed>21677750</pubmed></ref> "Gene targeting in embryonic stem cells has become the principal technology for manipulation of the mouse genome, offering unrivalled accuracy in allele design and access to conditional mutagenesis. To bring these advantages to the wider research community, large-scale mouse knockout programmes are producing a permanent resource of targeted mutations in all protein-coding genes. Here we report the establishment of a high-throughput gene-targeting pipeline for the generation of reporter-tagged, conditional alleles. Computational allele design, 96-well modular vector construction and high-efficiency gene-targeting strategies have been combined to mutate genes on an unprecedented scale. So far, more than 12,000 vectors and 9,000 conditional targeted alleles have been produced in highly germline-competent C57BL/6N embryonic stem cells. High-throughput genome engineering highlighted by this study is broadly applicable to rat and human stem cells and provides a foundation for future genome-wide efforts aimed at deciphering the function of all genes encoded by the mammalian genome."