Posted October 19, 2009
The Knockout Mouse Project was first proposed by Francis Collins, head of the National Human Genome Research Institute (NHGRI) of the NIH, to follow up the Human Genome Project. Scientists began to knock out individual genes in mice systematically and analyze the mouse's appearance and behavior to infer the missing gene's function. But the process was slow and complicated. On March 26, 2006, George Yancopoulos of Regeneron Pharmaceuticals discussed his group's technology, called VelociGene, for rapidly making genetic changes to mouse embryonic stem cells. This technology can be used to shorten the time it takes to generate knockout mice.
Use the tabs above to find a meeting report and multimedia from this event.
The Knockout Mouse Project
A trans-NIH initiative that aims to generate a comprehensive and public resource comprised of mice containing a null mutation in every gene in the mouse genome.
Austin, C. P., J. F. Battey, A. Bradley, et al. 2004. The knockout mouse project. Nat. Genet. 36: 921-924.
Bodine, S. C., E. Latres, S. Baumhueter, et al. 2001. Identification of ubiquitin ligases required for skeletal muscle atrophy. Science 294: 1704-1708.
Choi, G. B., H. W. Dong, A. J. Murphy, et al. 2005. Lhx6 delineates a pathway mediating innate reproductive behaviors from the amygdala to the hypothalamus. Neuron 46: 647-660.
DeChiara, T. M. 2001. Gene targeting in ES cells. Methods Mol. Biol. 158: 19-45.
DeChiara, T. M., R. B. Kimble, W. T. Poueymirou, et al. 2000. Ror2, encoding a receptor-like tyrosine kinase, is required for cartilage and growth plate development. Nat. Genet. 24: 271-274.
Gale, N. W., M. G. Dominguez, I. Noguera, et al. 2004. Haploinsufficiency of delta-like 4 ligand results in embryonic lethality due to major defects in arterial and vascular development. Proc. Natl. Acad. Sci. USA 101:15949-15954. FULL TEXT
Gale, N., G. Thurston, S. Hackett, et al. 2002. Angiopoietin-2 is required for postnatal angiogenesis and lymphatic patterning, and only the latter role is rescued by angiopoietin-1. Dev. Cell 3: 411-423.
Kasus-Jacobi, A., J. Ou, D. G. Birch, et al. 2005. Functional characterization of mouse mRdh11 as a retinol dehydrogenase involved in dark adaptation in vivo. J. Biol. Chem. 280: 20413-20420.
Lai, K. M., M. Gonzalez, W. T. Poueymirou, et al. 2004. Conditional activation of akt in adult skeletal muscle induces rapid hypertrophy. Mol. Cell. Biol. 24: 9295-9304. FULL TEXT
Lund, J. M., L. Alexopoulou, A. Sato, et al. 2004. Recognition of single-stranded RNA viruses by Toll-like receptor 7. Proc. Natl. Acad. Sci. USA 101: 5598-5603. FULL TEXT
Macdonald, L. E., K. E. Wortley, L. C. Gowen, et al. 2005. Resistance to diet-induced obesity in mice globally overexpressing OGH/GPB5. Proc. Natl. Acad. Sci. USA 102: 2496-2501. FULL TEXT
Oldridge, M., A. M. Fortuna, M. Maringa, et al. 2000. Dominant mutations in ROR2, encoding an orphan receptor tyrosine kinase, cause brachydactyly type B. Nat. Genet. 24: 275-278.
Sanes, J. R., E. D. Apel, R. W. Burgess, et al. 1998. Development of the neuromuscular junction: genetic analysis in mice. J. Physiol. Paris 92: 167-172.
Shrivastava, A., C. Radziejewski, E. Campbell, et al. 1997. An orphan receptor tyrosine kinase family whose members serve as nonintegrin collagen receptors. Mol. Cell 1: 25-34.
Sleeman, M. W., K. E. Wortley, K. M. Lai, et al. 2005. Absence of the lipid phosphatase SHIP2 confers resistance to dietary obesity. Nat. Med. 11: 199-205.
Valenzuela, D. M., A. J. Murphy, D. Frendewey, et al. 2003. High-throughput engineering of the mouse genome coupled with high-resolution expression analysis. Nat. Biotechnol. 21: 652-659.
Wortley, K. E., K. D. Anderson, K. Garcia, et al. 2004. Genetic deletion of ghrelin does not decrease food intake but influences metabolic fuel preference. Proc. Natl. Acad. Sci. USA 101: 8227-8232. FULL TEXT
Yuan, H. T., C. Suri, G. D. Yancopoulos & A. S. Woolf. 1999. Expression of angiopoietin-1, angiopoietin-2, and the Tie-2 receptor tyrosine kinase during mouse kidney maturation. J. Am. Soc. Nephrol. 10: 1722-1736.
George D. Yancopoulos, MD, PhD
George D. Yancopoulos is the president of Regeneron Research Laboratories and chief scientific officer of Regeneron Pharmaceuticals, a biopharmaceutical company that discovers, develops, and intends to commercialize therapeutic medicines for the treatment of serious medical conditions. He received his PhD in biochemistry and molecular biophysics and his MD from Columbia University. He is a member of the National Academy of Sciences.
Kiryn Haslinger is a science writer and editor with a masters in theoretical chemistry. Since working with James D. Watson on his book DNA: The Secret of Life as a research and editorial assistant, she has written freelance articles on science and scientific history.