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NIH Launches Attack on Mouse Genome

on 7 September 2006, 12:00 AM | | 0 Comments
Picture of mouse
Goodbye, genes.
A knockout mouse missing a gene for hair growth (left) sits next to a normal mouse.
Credit: MAGGIE BARTLETT/NHGRI

The National Institutes of Health (NIH) has kicked off its Knockout Mouse Project (KOMP), a massive effort to delete over a third of the genes in the mouse genome. Today, the institute named four centers that together will receive nearly $50 million over 5 years to create mutant cell lines and mice. The resource is expected to provide researchers with a mouse mutant for whatever disease or development gene they want to study.

Three of the centers--Children's Hospital Oakland Research Institute in California, the School of Veterinary Medicine at the University of California (UC), Davis, and the Wellcome Trust Sanger Institute in Hinxton, U.K.--will work together to make about 5000 unique knockouts. The fourth center, Regeneron Pharmaceuticals in Tarrytown, New York, plans to generate about 3500 additional mutants using technology it has developed for its drug-discovery program. "NIH has picked some great people," says Marina Picciotto, a mouse researcher at Yale University.

The NIH program is part of a global endeavor to knock out every gene in the mouse genome (Science, 30 June, p. 1862). In January, Europe and Canada embarked on the European Conditional Mouse Mutagenesis Program (EUCOMM) and the North American Conditional Mouse Mutagenesis Project, respectively, which have a combined goal of creating more than 30,000 knockouts in embryonic stem cells. China has plans for a similar resource. Mice and humans share similarity in some 25,000 genes, yet to date only about 11,000 different knockouts have been made. By coordinating their efforts, the projects hope to close this gap.

The Sanger Institute is also one of the leaders of the EUCOMM effort, but Sanger Director Allan Bradley says there will be no overlap between the two programs. "KOMP and EUCOMM researchers will be working side by side, but they'll each be targeting a different set of genes," he says.

Just which genes KOMP will go after will be decided by the Jackson Laboratory in Bar Harbor, Maine, which has received $2.5 million to help coordinate the project. Another $2.5 million will go to the University of Pennsylvania in Philadelphia and the Mount Sinai Hospital in Toronto to improve the performance of the reagents used by the KOMP centers.

Researchers should begin reaping KOMP's benefits in 6 to 9 months, says program director Colin Fletcher, when they can start ordering materials from Regeneron and UC Davis to make their own knockout mice. By next fall, he says, NIH will have set up one or more distribution centers that will quickly get knockouts into the hands of researchers who need them.

"That's going to save investigators lots of money and time and greatly accelerate the pace of mouse research," says M. Celeste Simon, a mouse researcher at the University of Pennsylvania Cancer Center. "It's a very wise investment for NIH."

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