The use of knockout mice as tools for studying a specific gene’s function within a physiological or disease system grew during the 1990s as many laboratories constructed models for their own research. After the mouse genome was sequenced in 2002, scientists realized the tremendous potential a full library of mouse knockouts could provide for studying gene function and human disease, given the genomic similarity of the two organisms. But the creation of such a library was too large an undertaking for any one institution or laboratory to conduct; a collaborative effort would be needed.
A coordinated venture would also create efficiency (saving money and time), improve availability, and ensure reproducibility of data through the standardization of models. In 2007, the International Knockout Mouse Consortium (IKMC) was formed with the support of the European Commission, the National Institutes of Health and Genome Canada. The process of creating embryonic stem cell lines for knockouts of each of the approximately 21,000 protein-coding genes in the mouse genome was begun through four programs: The Knockout Mouse Project (KOMP), the European Conditional Mouse Mutagenesis Program (EUCOMM), the North American Conditional Mouse Mutagenesis Project (NorComm), and the Texas A&M Institute for Genomic Medicine (TIGM).
Through the sharing of technologies, coordination of production plans and joint resolution of issues related to archiving and distributing resources, the IKMC has had great success and will soon reach its goal.
With ES cell lines already created for more than two-thirds of the mouse genome, in 2011 the National Institutes of Health (NIH) launched the second phase of this project, the Knockout Mouse Phenotyping Program, or KOMP2: generating and phenotyping mice for over 5,000 knockout ES cell lines. Phenotyping, which will measure biological information from appearance and behavior to biochemical characteristics, will employ a standardized battery of analyses to obtain consistent data on traits affected by the deleted genes.
The NIH has funded three KOMP2 centers to convert the ES cells into mice and rigorously document their phenotypes:
- The Jackson Laboratory
- The BaSH Consortium (Baylor College of Medicine, The Wellcome Trust Sanger Institute and MRC Harwell)
- The DTCC Consortium (University of California at Davis, The Toronto Center for Phenogenomics, Children’s Hospital Oakland Research Institute (CHORI) and Charles River Laboratories)
All of the data generated by the KOMP2 program are collected and made public by a central Data Coordination Center Database located at EBI-Hinxton, with support from Mouse Genome Informatics.
How to cite this resource
The JAX KOMP2 program is funded by multiple grants from the National Institutes of Health, through the NIH Common Fund.
- Please acknowledge U42OD011185 in research using mice produced by the JAX KOMP program (High-throughput production and cryopreservation of knockout mice).
- Please acknowledge U54HG006332 in research benefiting from data provided by the JAX KOMP Phenotyping Center