Advancing Health Research through Improved Models
To uncover the role of genetic changes in the development of hereditary diseases such as cancer, it is possible to “knock out” selected genes in mice either by removing them, or selectively turning them on or off. Known as gene trapping or gene targeting, this process is accomplished by creating mouse embryonic stem cells in which a single gene has been replaced with a “null” gene—a non-functioning placeholder or a “conditional” gene-a modified gene for experimental testing. As the knock out mice grow to adulthood, researchers can study the effects of the altered gene.
The North American Conditional Mouse Mutagenesis (NorCOMM) project brought together research groups from across Canada, the US and Europe to develop mouse models for genomics health research and drug discovery.
The mouse is a critical model organism because 99 percent of the genes in mice are also present in humans. NorCOMM established a resource of mutant mouse embryonic stem cell lines that allows researchers to study the function of virtually any gene of interest. This resource is helping to elucidate the role of genetic predisposition in development, adverse drug reactions, obesity, diabetes, cancer, and other major diseases. As more industry, academic and government labs use mouse models for health research, the economic and social benefits of NorCOMM will perpetuate well into the future.
The process to isolate just one gene, which used to take up to two years of specialized work, has been streamlined to produce up to 1,000 isolations in one month. Some genes are more easily trapped than others, but after the mouse genome sequence became available for NorCOMM researchers, new methods were devised to target specific genes of interest to industry, academic and government labs. As the NorCOMM project gained momentum, an international effort came together; the International Knock out Mouse Consortium (IKMC). The IKMC enabled NorCOMM to coordinate efforts with international partners, the European Conditional Mouse Mutagenesis (EUCOMM) Program, the Knockout Mouse Project (KOMP) (National Institutes of Health - USA), and the Texas A&M Institute for Genomic Medicine (TIGM) to focus on high-throughput targeted gene knockouts, prioritizing requests from researchers and biotech companies worldwide. To date, the IKMC effort has developed over 36,180 knock out ES cell lines and over 2,150 knock out mouse lines.
- Over 220 knockout cell lines have been incorporated into external research programs in over 18 countries and in 10 Canadian academic labs.
- There have been 63 peer-reviewed publications using IKMC resources. 41 of these were released in 2012 and this number is expected to grow rapidly as more end-users access the resource.
- Two biopharmaceutical firms have incorporated NorCOMM cell lines into their drug discovery and validation pipelines.
- The National Institutes of Health estimates that any user will save $20-50K in development costs for each cell line ordered from NorCOMM.
- NorCOMM researchers leveraged over $30 million in additional funding to enhance the utility and use of the embryonic stem cell resource.
- The International Mouse Phenotyping Consortium (IMPC) has been developed to help researcher utilized the IKMC resource. The IMPC will determine the function of every gene in the mouse genome. These mice will be preserved in repositories and made available to the scientific community.
Geoff Hicks, University of Manitoba
Janet Rossant, University of Toronto
Carolyn Ashley, Genome Prairie
Lauryl Nutter, CMHD
Genome Canada Contribution:
Provincial Funding (MB):
Other Funding Partners:
Genome Canada Competition III