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$28.3M federal grant to JAX for Knockout Mouse Project to reveal gene function

By Joyce Peterson

The National Institutes of Health (NIH) will award a total of $28,305,235 to The Jackson Laboratory (JAX) over five years to fund phase 2 of the Knockout Mouse Production and Phenotyping Project (KOMP2).

JAX Professor and Janeway Distinguished Chair Robert Braun, Ph.D., Senior Research Scientist Stephen Murray, Ph.D., and Research Scientist Karen Svenson, Ph.D., are the principal investigators of the grant.

“Mice and humans share approximately 20,000 genes,” Braun says, “but scientists have little or no data for more than half of these genes.” He says that scientists around the world have been working together since 2006 to generate a targeted knockout mutation for every gene in the mouse genome. “Deleting individual genes in this way provides valuable clues to the genes’ function.”

JAX and two other NIH funded centers are part of a worldwide effort, the International Mouse Phenotyping Consortium (IMPC), to genetically and systematically determine the function of every mammalian gene, one gene at a time. The consortium is engaged in the immense task of producing and phenotyping (collecting physiological data from) these mice. Mouse models of genes with common functionality between mice and humans can lead to new models of human disease, which are useful for drug screening, preclinical studies and deeper understanding of biological and disease mechanisms.

Under the new grant, Braun says, JAX will take advantage of powerful new gene editing technology, known as CRISPR/Cas9, to generate, breed, cryopreserve and clinically assess the health and well-being of 1,000 lines of mice. The research team will work with the scientific community to select genes of exceptional interest, genes for which little is presently known, and genes predicted to function in select pathways.

For each of the new mouse lines, JAX will assess body weight and composition, metabolic and physiological parameters, and behavioral and cognitive function at several age points, and make both the mice and the resulting data available to the worldwide scientific community prior to publication.

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