Diagram showing overview of the KOMP2 phenotyping process. Building on resources derived from IKMC, standardized phenotyping of mutant mouse strains will be performed and data stored in a centralized database.
The laboratory mouse has been considered the premiere experimental model of human biology and disease since 1902 when it was first used to demonstrate how genetic traits could be transferred from parents to offspring via classical or “Mendelian” inheritance in mammals. In just over a century, an impressive array of genetic tools, reagents and processes has been developed in the mouse, including:
- Genetically similar or homozygous inbred strains,
- Monoclonal antibodies,
- Gene knockouts or animals engineered to carry a gene that has been made inactive or “knocked out”, and
- Transgenesis models or mice who have had a new gene – called a transgene – added so they will display a new trait and transmit that trait to their offspring.
Evidence that mice have played a key role in biomedical research is provided by the fact that at least 18 Nobel prizes have been awarded for work done using the mouse. Most recently, the 2007 Nobel Prize was awarded to Mario Capecchi, Martin Evans, and Oliver Smithies for their discovery of the "principles for introducing specific gene modifications in mice by the use of embryonic stem (ES) cells.” This technology has enabled gene knockout experiments that have elucidated the roles of thousands of genes in embryonic development, adult physiology, aging, and disease.
Recognizing the value and utility of a readily accessible, genome-wide collection of knockouts as the lynchpin to determine how mammalian genes function, several international programs were launched in 2006 to build such a resource. Partners in this effort include the NIH funded Knockout Mouse Program (KOMP), the European Conditional Mouse Mutagenesis Program (EuCOMM) funded by the European Commission, and the North American Conditional Mouse Mutagenesis Project (NorCOMM) funded by Genome Canada. Collectively, these programs have created over 15,000 knockouts in the form of embryonic stem (ES) cells, and they are on track to complete the resource by the end of 2011. This collection is complemented by the Texas A&M Institute for Genomic Medicine’s collection of mouse gene traps — mouse knockouts created using high-throughput approaches to introduce mutations across the mouse genome — resulting in over 17,000 knockouts being available to the scientific community.
The new Common Fund KOMP2 program will build upon this resource by expanding the efforts to characterize the mutant strains. Planning activities were held in fiscal years 2010-11 to shape the program, and awards were made in late fiscal year 2011 (see Funded Research).