|Researchers to Gain Wider Access to Knockout Mice
Trans-NIH Effort Provides New Models for Understanding Human Disease
Bethesda, Maryland — The National Institutes of Health
(NIH) today announced contracts that will give researchers unprecedented access
to two private collections of knockout mice, providing valuable models for the
study of human disease and laying the groundwork for a public, genome-wide library
of knockout mice.
Under terms of three-year contracts jointly funded by 19 NIH institutes, centers
and offices, Deltagen Inc. of San Carlos, Calif., and Lexicon Genetics Incorporated
of The Woodlands, Texas will provide NIH and its scientific partners with access
to extensively characterized lines of mice in which a specific gene has been
disrupted, or “knocked out.” In the first year of the contract, NIH will expend
about $10 million to acquire about 250 lines of knockout mice.
For each mouse line, the contractors will provide not only the mouse line itself,
but also detailed, objective data on the impact of the specific gene deletion
on the mouse’s phenotype, which includes appearance, health, fitness, behavior,
ability to reproduce, and radiological and microscopic data. Such comprehensive
information on such a large group of mice has never been available to public
sector researchers, and is expected to greatly accelerate efforts to explore
gene functions in health and disease.
“Our decision to procure these knockout mouse lines and data and make them available
to the research community will yield tremendous benefits, both in the short and
long terms,” said NIH Director Elias A. Zerhouni, M.D. “This trans-NIH initiative
will place important mouse models into the hands of researchers,
speeding advances in the understanding of human disease and the development of
new therapies. It also represents a significant step in the direction of launching
an international project to systematically knock out all genes in the mouse.”
Since recombinant DNA technology was used to create the first such animals in
the early 1980s, knockout mice have proven to be one of the most powerful tools
available to study the function of genes and to create mouse models of human
disease. Researchers have produced knockout mice with characteristics similar
to humans suffering from a wide range of disorders, including cancer, heart disease,
neurological disorders and even obesity.
The process used by NIH to select the mouse lines involved a rigorous scientific
review process that evaluated information on the knocked out gene, the reliability
of the method used to produce the knockout, and whether the mouse line possesses
a “reporter” gene which enables researchers to analyze the pattern of the knockout
gene’s expression in various mouse tissues.
“This is exciting news for all researchers working to understand the complex
underpinnings of human biology in health and disease. Knockout mice provide one
of the quickest, most cost effective ways to explore gene function. It is essential
that we make it possible for more researchers to tap into this power,” said James
Battey, M.D., Ph.D., Director of the National Institute on Deafness and Other
Communication Disorders. Dr. Battey serves as chair of the Trans-NIH Mouse Initiative,
which develops priorities for mouse genomics and genetic resources at NIH.
The new contracts provide NIH with irrevocable, perpetual, worldwide, royalty-free
licenses to use and distribute to academic and non-profit researchers these lines
of knockout mice. The mouse lines, which will be stored in the form of frozen
embryos, frozen sperm and frozen embryonic stem (ES) cells, will be delivered
to NIH-funded mouse repositories that supply
mice to universities, medical schools and research labs all over the world. When
researchers express interest in obtaining a certain knockout mouse line, the
repositories will send them live mice, frozen embryos, sperm, and/or ES cells,
so they can study the mice in their own labs. All data on the mice will be made
available to researchers worldwide without restriction in publicly available
databases on the Web.
Under the license agreements with Deltagen and Lexicon, researchers who receive
the knockout mice lines are free to publish any results from research involving
the line and also to seek patent or other intellectual property protection for
any of inventions or discoveries resulting from such research.
The 19 NIH institutes, centers and offices contributing to the contracts 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.
In order to build upon the acquisition of knockout mice available from the private
sector, the NIH in September issued a set of requests for applications to establish
a Knockout Mouse Project. The ambitious goal of this trans-NIH program is to
produce a comprehensive resource of mouse mutants in which every gene in the
mouse genome has been knocked out. The resource will serve to further the value
of the mouse as a powerful and important tool in the study of human health and
For more information on what knockout mice are, how they are made and what they
are used for, go to http://www.genome.gov/12514551.
The National Institutes of Health (NIH) — The Nation's Medical Research
Agency — includes 27 Institutes and Centers and is a component of
the U. S. Department of Health and Human Services. It is the primary Federal
agency for conducting and supporting basic, clinical, and translational medical
research, and it investigates the causes, treatments, and cures for both common
and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.