Baylor receives $12 million grant for third phase of Knockout Mouse Phenotyping Program

Researchers at Baylor College of Medicine have received a grant for more than $12 million from the National Institutes of Health for a third five-year phase of the Knockout Mouse Phenotyping Program (KOMP2). KOMP2 is part of the International Mouse Phenotyping Consortium (IMPC), a worldwide effort to create a mouse model for every protein-coding gene in the mouse genome and characterize each gene’s function.

“We knock out, or turn off, one gene in each mouse model in order to understand the basic biological function of that gene,” said Dr. Jason Heaney, co-principal investigator of the study, associate professor of molecular and human genetics and director of the Center for Precision Medicine Models at Baylor. “Once we know what a gene does, we can start to understand how a variation in that gene contributes to disease on a mechanistic level.”

Together, IMPC teams have created unique gene knockout mouse lines for more than 10,000 genes and characterized the phenotypes of nearly 9,000 of those genes. All the data is publicly available online for use in scientific research. Approximately 75% of protein-coding genes in the human genome have been catalogued in corresponding knockout mouse models. This final round of funding for KOMP2 is part of an effort to complete the rest of the protein-coding genome.

Baylor is one of three KOMP2 sites, along with the University of California, Davis and the Jackson Laboratory in Bar Harbor, Maine. Each KOMP2 site is expected to produce and characterize an additional 400 knockout mouse lines over the next 5 years.

“Our team at Baylor will draw on the strength of our human disease gene discovery program and our top-funded genetics department to create knockout mice that can be used as resources to verify gene-disease association and to understand how these genes cause disease and potentially can be used for pre-clinical therapeutic studies,” said Dr. Mary Dickinson, co-principal investigator of the study, senior vice president and dean of research at Baylor. “Our KOMP2 research also will benefit from connections with Baylor’s Center for Precision Medicine Models and Undiagnosed Diseases Center.”

“KOMP2 will help us understand genetic contribution to rare diseases, Mendelian diseases and more common diseases like cardiovascular disease and diabetes,” Heaney said. “We are developing tools to help clinicians and patients get answers and to improve the lives of people who suffer from genetic diseases.”

Dickinson is professor of molecular and human genetics and Kyle and Josephine Morrow Endowed Chair of molecular physiology and biophysics. Heaney is co-leader of the advanced in vivo cancer models shared resource at the Dan L Duncan Comprehensive Cancer Center. Other Baylor researchers involved in this work include: Dr. John Seavitt, Dr. Denise Lanza, Dr. Rodney Samaco, Dr. Surabi Veeraragavan, Dr. Christopher Ward, Dr. Chih-Wei (Logan) Hsu and Dr. Audrey Christiansen.

This research is funded by NIH grant UM1 HG006348.