|NIH Launches Effort to Place More Knockout Mice in Public
Bethesda, Maryland — As part of its ongoing effort to
build a public, genome-wide library of “knockout” mouse models for the study
of human disease, the National Institutes of Health (NIH) today awarded $800,000
to two public mouse repositories to acquire genetically engineered mouse lines
not yet widely accessible to researchers.
In the two decades since recombinant DNA technology was first used to produce
lines of mice in which specific genes have been disrupted, or “knocked out,” such
mice have proven to be one of the most powerful tools available to study the
function of genes and to create animal models of human disease. Researchers have
generated knockout mice that serve as useful models of human diseases, such as
cancer, heart disease, neurological disorders and even obesity.
“NIH is committed to making knockout mouse models more widely accessible to
the biomedical research community,” said National Institute on Deafness and Other
Communication Disorders (NIDCD) Director James Battey, M.D., Ph.D., who is chairman
of the Trans-NIH Mouse Initiative. “Getting these valuable models into the hands
of a wide range of researchers will serve to accelerate our efforts to develop
new strategies for understanding and treating human disease.”
NIH policy requires that mouse lines created through NIH-funded research be
made available to the scientific community after researchers publish papers describing
their work. However, the obligation to maintain mouse lines and supply them to
others can be burdensome for small laboratories and individual researchers. To
facilitate sharing, the National Center for Research Resources (NCRR) supports
a network of public repositories that archive and distribute mouse strains. The
network includes the Mutant Mouse Regional Resource Centers (MMRRC) at the University
of California, Davis, the Harlan/University of Missouri facility in Columbia,
the University of North Carolina, Chapel Hill, and the Jackson Laboratory in
Bar Harbor, Maine.
Depositing mice in centralized repositories ensures ready availability of lines
at a reasonable cost, standardizes the animals’ health status and guarantees
long-term preservation of lines. However, more than 3,000 of the approximately
4,000 knockout mouse lines described in the scientific literature have not yet
been placed in public repositories. To increase the availability of such models,
the NIH Knockout Mouse Project has initiated an effort to encourage more NIH-supported
researchers to place the knockout mouse lines that they have created into public
Using funds supplied by the NIH Neuroscience Blueprint and the National Institute
of Allergy and Infectious Diseases (NIAID), the NCRR today awarded a total of
$800,000 for deposition of existing knockout mice to MMRRCs at the University
of California, Davis and the Harlan/University of Missouri facility. Additionally,
all of the NCRR-supported mouse repositories will use their existing capacity
to further increase the number of existing mice that can be deposited. In total,
NIH anticipates that more than 300 existing mouse mutants will be deposited and
made available to the research community over the next two years.
NIH currently is working with the research community to develop a prioritized
list of mice that can be collected under this program. Drawing upon that list,
the researchers will be asked to submit the mouse lines to the repositories,
which will maintain and replenish them, and distribute the lines to the biomedical
research community upon request.
“We are very pleased that the NCRR’s network of mouse repositories will be working
together to carry out this effort. The network has an excellent track record
of acquiring, maintaining and distributing mutant mouse lines. By leveraging
existing infrastructure and resources, we will be able to make these mice available
to researchers in a timely, cost-effective manner,” said NCRR Acting Director
Barbara M. Alving, M.D.
The Knockout Mouse Project is a trans-NIH initiative that aims to produce, in
the next five years, a comprehensive resource of mouse mutants in which each
of the approximately 20,000 genes in the mouse genome has been knocked out. The
resource will greatly enhance the already considerable value of the mouse in
the study of human health and disease.
In October 2005, NIH laid the foundation for the project with contracts that
provided NIH and the research community with access to a set of very well-characterized
knockout mouse lines created by Deltagen, Inc. of San Carlos, Calif., and Lexicon
Genetics Incorporated of The Woodlands, Texas. As part of this procurement, NIH
also obtained a great deal of data on the observable characteristics, or phenotype,
of each of the mouse lines. In the first year of the three-year contract, NIH
has expended about $11 million to acquire about 250 lines of these well-characterized
knockout mice. Researchers can obtain information on what lines are available
and how to order them at http://www.nih.gov/science/models/mouse/deltagenlexicon/list.html.
Later this summer, through the National Human Genome Research Institute (NHGRI),
the trans-NIH initiative will award a set of cooperative agreements to support
the central component of the Knockout Mouse Project. These cooperative agreements,
which will total up to $50 million over 5 years, will be aimed at making maximum
progress toward the completion of a comprehensive resource of knockout mice lines
representing all genes in the mouse genome. Awardees will use a variety of techniques,
such as gene targeting, gene trapping or transposon-mediated mutagenesis, to
systematically create new knockout mouse lines for the thousands of genes not
included in the effort to deposit existing knockout mouse lines or the contracts
with Deltagen and Lexicon. For more details on the techniques used to make knockout
mice, visit http://www.genome.gov/12514551.
“It will take an enormous amount of work to build this knockout mouse resource,
but we are confident the effort will be well worth it. This resource will enable
many, many more researchers to tap into the power of knockout mice for exploring
gene function, which in turn will speed our efforts to improve human health,” said
NHGRI Director Francis S. Collins, M.D., Ph.D. “It is exciting that so many different
components of NIH have pulled together to support this important project.”
The 19 NIH institutes, centers and offices contributing to the Knockout Mouse
Project are: National Center for Complementary and Alternative Medicine, NCRR,
National Eye Institute, NHGRI, National Heart, Lung and Blood Institute, National
Institute on Aging, National Institute of Alcohol Abuse and Alcoholism, NIAID,
National Institute of Arthritis and Musculoskeletal and Skin Diseases, National
Institute of Child Health and Human Development, NIDCD, 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.
For more information on the Knockout Mouse Project, visit http://www.nih.gov/science/models/mouse/knockout/index.html.
High-resolution photos of knockout mice are available at: http://www.genome.gov/pressDisplay.cfm?photoID=5006.
NCRR provides laboratory scientists and clinical researchers with the environments
and tools they need to understand, detect, treat, and prevent a wide range
of diseases. For more, visit www.ncrr.nih.gov.
NHGRI supports the development of resources and technology that will accelerate
genome research and its application to human health. For more, visit www.genome.gov.
The NIH Neuroscience Blueprint provides a framework for enhancing cooperation
among 15 NIH Institutes and Centers, with an emphasis on supporting and making
broadly available tools and resources for the neuroscience research community.
For more, visit http://neuroscienceblueprint.nih.gov/
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 www.nih.gov.