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Knockout Mouse Project

Children's Hospital & Research Center Oakland is leading one of two teams in an international effort to produce thousands of genetically altered mice for a study to understand the role of individual genes in human health. Other members of the team represent the School of Veterinary Science at the University of California, Davis and the Wellcome Trust Sanger Institute in Hinxton, England. The National Institutes of Health (NIH), announced the selection of the hospital's research institute for the Knockout Mouse Project (KOMP) on September 7, 2006.

The $50 million initiative funded by the NIH is intended to help researchers explore the functions of 10,000 mouse genes. Humans and mice share the same characteristics for most of the 10,000 mouse genes identified for this study. Researchers hope to catalogue and confirm the functions of these genes and identify the disease consequences if these genes are defective. Since human and mice genes are similar, it is hoped that by inactivating mouse genes, one-by-one, the altered mice will yield clues about the function of human genes and their similar roles in human diseases.

"The process is a long one, but the rewards are immeasurable," said Pieter de Jong, Ph.D., Children's Hospital Oakland Research Institute scientist and principle investigator for KOMP. "We're at the forefront of understanding the pathology of human genes. By knocking out each gene one-by-one, we will be able to create a central resource for researchers and scientists to use and study," said Dr. de Jong.

Children's Hospital Oakland Research Institute has a recombinant DNA library with more than 30 million DNA samples that are used in research programs around the world. The research institute's DNA library has become a major resource for ongoing global research in the genetics of human diseases. The recombinant DNA library is, for example, being used in Oakland to investigate the genetic differences that make certain peopl e susceptible to inherited forms of Lou Gehrig's Disease.

For the new "KOMP" project, Children's Hospital Oakland will create the genetic material that will be used to knockout or "inactivate" mouse genes. Scientists at the Wellcome Trust Sanger Institute in Hinxton, England will insert the altered genes into the embryonic stem cells derived from the mice. UC Davis will use the altered embryonic stem cells to create adult mice with one missing gene, which are referred to as "knockout mice."

This NIH-funded project will work closely with similar efforts in Canada and Europe to inactivate and study additional mouse genes. The projects provide new standards to ensure that scientists will be working from the same tested and proven methodology. Eventually, the project may expand to include large scale studies related to the pathology of the 10,000 knock-out mouse strains. For now, scientists say there is much to be learned from the current study.


Source:Children's Hospital & Research Center at Oakland

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