In newly patented process, The Jackson Laboratory "freezes" genetic variation in mice
| Date: September 22, 2009 |
Bar Harbor, Maine -- The U.S. Patent and Trademark Office has awarded The Jackson Laboratory a patent for a process that effectively prevents random change or "genetic drift" in its inbred mouse colonies.
Thanks to the close match between human and mouse genes, researchers around the world use mouse models to study human biology and diseases. Today more than 4,000 mouse models are available from The Jackson Laboratory, each with a very specific genetic profile.
However, just a few of these models -- standard inbred strains -- represent the vast majority of mice used in research and are consequently bred in large numbers. Because "evolution happens" even among genetically identical animals, there's always the chance of random new mutations arising over time or place in these mouse colonies, potentially introducing unknown variables into researchers' experiments.
"Some of these mutations will be visible and easy to detect," notes Michael Wiles, Ph.D., senior director of technology transfer and development at the Laboratory. "However, most will be invisible. This means that over time the mouse model will change its genetic consistency, so if you do an experiment now and you do it again in 10 years, you might get different results."
The Jackson Laboratory has rigorous processes in place to detect and screen out the effects of random mutations in its foundation mouse colonies, Wiles says. The newly patented Genetic Stability Program (GSP), which Wiles and Jackson colleagues Robert Taft, Ph.D., and Eva Eicher, Ph.D., devised in 2003, literally freezes genetic variation in its tracks, by rebooting the production colonies with frozen embryos or gametes from specially prepared stocks every five generations. The stocks are set up to give a 25-year supply.
Watch a video interview with Drs. Taft and Wiles (4:48)
The innovation allows the Laboratory to reduce the number of generations in its inbred foundation stocks, thus stopping the accumulation of mutations and revolutionizing the uniformity of the mouse as a research tool.
The first inbred mouse strains to be included in the GSP are those, such as the famous C57BL/6J "Black 6," with genomes that have been fully or partially sequenced. The Laboratory is also continually adding new strains to this list. These are the strains that researchers typically start with to develop new mouse models of specific diseases. Because a given engineered mutation can show very different characteristics on different genetic backgrounds, the choice of strain is all-important, and any random variations in that strain can jeopardize the validity of a study.
"With the Genetic Stability Program," says Taft, director of the Laboratory's Reproductive Sciences group, "we're helping to ensure the genetic integrity of the mice that are distributed from here for at least a couple of decades, improving the consistency of research results for many years to come."
The Jackson Laboratory is an independent, nonprofit biomedical research institution based in Bar Harbor, Maine, with a facility in Sacramento, Calif. Its mission is to discover the genetic basis for preventing, treating and curing human diseases, and to enable research and education for the global biomedical community.
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