NEW YORK (GenomeWeb News) – The National Institutes of Health has awarded nearly $52 million to launch the Knockout Mouse Project, a comprehensive resource of knockout mutations in the mouse genome, the agency said today.
Knockout mice are lines of mice in which specific genes have been completely disrupted. Systematic disruption of each of the 20,000 genes in the mouse genome will allow researchers to determine the role of each gene in normal physiology and development, NIH said.
Two awards, totaling up to $47.2 million over five years, were granted to Regeneron Pharmaceuticals and a collaborative team from Children’s Hospital Oakland Research Institute, School of Veterinary Medicine at University of California, Davis, and the Wellcome Trust Sanger Institute to create a combined collection of mouse embryonic stem cell lines in which 8,500 genes have been knocked out by gene targeting.
In addition, the Jackson Laboratory received a five-year cooperative agreement totaling $2.5 million to establish an NIH Knockout Mouse Project data coordination center to collect information to track the scheduling and progress of knockout production, to serve as a central information resource for known knockout mutants, and to integrate with other databases that contain mouse DNA sequences.
The University of Pennsylvania and the Samuel Lunenfeld Research Institute of Mount Sinai Hospital in Toronto received a total of $2.5 million to improve the efficiency of methods for creating knockout lines. The teams will developing methods suitable for high-throughput gene targeting or trapping in C57BL/6, the strain of mouse used most widely by the scientific community.
Regeneron will receive funds to optimize its existing ES cell line for the C57BL/6 strain and its proprietary growth medium, both of which will be supplied for use in the project.
NIH will issue a solicitation for a program to implement a Knockout Mouse Project repository, which will be funded in the next year.
The Knockout Mouse Project will work closely with Canada’s North American Conditional Mouse Mutagenesis Project and Europe’s European Conditional Mouse Mutagenesis Program. The programs aim to create a mutation in each of the approximately 20,000 protein-coding genes in the mouse genome. While academic researchers have created mouse knockouts around the world, there are overlaps. The three projects will coordinate to avoid more overlaps.
So far, academic researchers have created mouse knockouts of about 4,000 genes, and the International Gene Trap Consortium has developed a random disruption strategy to mutate 8,000 mouse genes. Due to some overlap between these efforts, about 15,000 genes remain to be knocked out in the mouse genome, NIH said.
The Knockout Mouse Project spans a number of NIH institutes, including NCRR, National Eye Institute, NHGRI, 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, NIDCD, National Institute of Dental and Craniofacial Research, NIDA, 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 Diabetes and Digestive and Kidney Disease, National Cancer Institute, and the Office of AIDS Research.
More information on the Knockout Mouse Project is here.
A fact sheet is here.