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) 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 repositories.
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.
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.
"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."