WINSTON-SALEM, N.C. – Wake Forest University Baptist Medical Center has set up a new laboratory to develop special mice to model human disease and treatments and tell scientists more about the function of human genes.
“This technology can lead to the development of a model for studying human disease and treatment strategies,” said Liqing Yu, M.D., Ph.D., director of the Transgenic Mouse Core Facility.
With the completion of the human genome project, scientists have identified all the genes in humans, but they don’t know what many of these genes do.
“We need to study the function of the genes,” said Yu, assistant professor of pathology - comparative medicine. “The most direct way of studying the function of a gene is through a mouse model.”
The mice are produced using genetic engineering to either insert an extra gene – these are called transgenic mice – or to create mice that are missing a gene – known as knockout mice.
Yu, a native of China, developed one of the first transgenic mice in China. He was recruited from the University of Texas Southwestern Medical Center in Dallas both to direct the transgenic program and to join the research group that studies cholesterol and hardening of the arteries.
With transgenic mice, a gene that scientists want to study is injected at the one-cell stage of development. All cells in the resulting mouse carry the extra gene, which leads to overproduction of whatever protein the gene produces. “Then we can examine what has changed.”
Yu said the technology could introduce a human gene into a mouse model and determine what function that human gene might have in humans.
In knockout mice, a particular gene is made nonfunctional and scientists study the resulting changes.
Yu said that these genes can be tested first in test-tube studies, but “eventually you have to study the gene function in a living animal model.”
Yu said the facility has already produced three transgenic mouse lines and are at the first stages of producing knockout mice.
“We hope to do more than 30 transgenic and knockout mice lines a year,” he said.
Wake Forest Baptist scientists have been studying genetically engineered mice for more than 15 years, especially in studies of high blood pressure, More recently, scientists found that one enzyme called ACAT2 is involved in the development of atherosclerosis – hardening of the arteries -- and another enzyme, LCAT, helps prevent atherosclerosis. They have helped prove this with knockout mice When the ACAT2 gene is knocked out, there is no atherosclerosis. Conversely, if the LCAT gene is knocked out, atherosclerosis increases
But these animals were engineered elsewhere, at places like the University of North Carolina, the University of Alabama at Birmingham and the University of Cincinnati. Being able to develop the mice on-site will help speed up the research process.
Richard St. Clair, Ph.D., professor of pathology and head of the Section on Comparative Medicine, led the effort to establish the new facility. He said researchers in just about every area of basic research now use transgenic or knockout mice or are planning to do so soon.
“This is an institutional facility designed to serve all the faculty of the medical school,” he said
“We are very fortunate to have Tanya Paschke supervising the Transgenic Mouse Core Facility,” said Yu. Paschke has 15 years experience and has supervised similar facilities at San Diego State University and at Scripps Research Institute in La Jolla, Calif.
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About Wake Forest University Baptist Medical Center: Wake Forest Baptist is an academic health system comprised of North Carolina Baptist Hospital and Wake Forest University Health Sciences, which operates the university’s School of Medicine. The system comprises 1,298 acute care, psychiatric, rehabilitation and long-term care beds and is consistently ranked as one of “America’s Best Hospitals” by U.S. News & World Report.