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NIH Receives Donation of Knockout Mice Collection Used To Study Secreted
and Transmembrane Proteins

Two mice, one black, one whiteIt's not every day that you get something useful at no charge.

But if you're a researcher studying genes that produce secreted and transmembrane proteins, today is your day. A full 472 knockout mouse lines — all extensively characterized (phenotyped) — are now publicly available from the National Institutes of Health's Mutant Mouse Regional Resource Center (MMRRC) at the University of California, Davis. Distribution of the lines is supported by the National Center for Research Resources (NCRR) and the NIH-funded Knockout Mouse Project (KOMP) repository, operated by UC Davis and the Children's Hospital Oakland Research Institute in Oakland, Calif.

Knockout mouse lines have served as valuable models to study a range of human conditions, from obesity and heart disease to diabetes and substance abuse. In knockout laboratory mice, researchers have inactivated, or "knocked out", a gene with an artificial piece of DNA. This helps scientists infer what a gene normally does by understanding what goes wrong when its function is disrupted.

The mouse library was recently donated by Genentech of San Francisco and Lexicon Pharmaceuticals of The Woodlands, Texas. It had been developed as part of a research collaboration by the two groups to study a set of genes that encode secreted and transmembrane proteins, an important class of drug targets.

The researchers recently published a description of the knockout mouse collection in the July 2010 issue of Nature Biotechnology. All of the knockout mice lines were initially screened to identify potential defects involved in metabolism, bone metabolism, or the development of cancer, as well as to establish whether the knocked out genes had a function in the cardiovascular, immune or neurological systems.

The researchers further characterized the knockout mice to identify critical biological processes in which the secreted and transmembrane proteins were involved, such as metabolism, neurology development and angiogenesis, the process of growing new blood vessels in the body.

Of 472 genes knocked out in the mice, 98 overlap with human genes for rare single gene genetic disorders in the Online Mendelian Inheritance of Man, a database operated by the NIH National Library of Medicine that describes rare single gene disorders. For example, seven mouse genes appear to be essential in normal hearing, thus providing new animal models that may be valuable in understanding hereditary deafness.

According to Andrew Peterson, Ph.D., Associate Director of Molecular Biology at Genentech and an author on the Nature Biotechnology paper, the donation of the knockout mice was possible because the research project for which they were bred reached its natural end point. "Now that our findings are published, donating the knockout library to NIH allows other scientists to study the mice to see what additional biological insights might be gleaned from them," said Dr. Peterson.

The NIH KOMP is a trans-NIH effort led by the National Human Genome Research Institute (NHGRI) to build a comprehensive and publicly available resource of knockout mutations for 8,500 genes in the mouse genome. A parallel effort, the International Knockout Mouse Consortium, is also being undertaken by researchers around the world to make knockout mice publicly available for the remainder of the total estimated 21,000 genes in the mouse genome.

"Sharing resources and information among members of the biomedical research community has been a core component of NIH's Knockout Mouse Project," said National Institute on Deafness and Other Communication Disorders Director James Battey, M.D., Ph.D., who is chairman of the Trans-NIH Mouse Initiative. "We're grateful to Genentech and Lexicon Pharmaceuticals for continuing that spirit of sharing and cooperation as we work to generate new knowledge about human diseases and their potential treatment."

NHGRI's KOMP Program Director Colin Fletcher, Ph.D., helped facilitate the transfer of the mouse knockout library and associated phenotype information from the companies to the MMRRC and KOMP repositories using funding made available to KOMP by the National Institute of Allergy and Infectious Diseases and the NIH Neuroscience Blueprint. Genentech and Lexicon Pharmaceuticals also contributed to the cost of transferring the mice.

The NIH Common Fund recently launched a new program called Knockout Mouse Phenotyping Project (KOMP2) that will be funded starting in fiscal year 2011. KOMP2 will provide knockout mice that include standardized, high-quality, broad phenotype information. This will enable researchers to select knockout mice most suited to their research.

Dr. Fletcher said, "The donation by Genentech and Lexicon Pharmaceuticals of these well-characterized knockout mice is a key first step toward this goal."

For more information on the NIH KOMP, go to: NIH Knockout Mouse Project (KOMP).

The 19 NIH institutes, centers and offices contributing to the NIH KOMP are: National Center for Complementary and Alternative Medicine, National Center for Research Resources, National Eye Institute, National Human Genome Research Institute, National Heart, Lung and Blood Institute, National Institute on Aging, National Institute of Alcohol Abuse and Alcoholism, National Institute of Allergy and Infectious Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institute of Child Health and Human Development, National Institute on Deafness and Other Communication Disorders, National Institute of Dental and Craniofacial Research, National Institute on Drug Abuse, National Institute of Environmental Health Sciences, National Institute of General Medical Sciences, National Institute of Mental Health, National Institute of Neurological Disorders and Stroke, National Institute of Nursing Research, and the Office of AIDS Research.

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Last Updated: November 8, 2012

Last updated: November 08, 2012