Designer mice to deliver

August 1, 2001

Suzanne Johnson

In the old Warner Brothers cartoons, Sylvester the Cat is continually being pummeled by a giant killer mouse wearing boxing gloves. (Of course, to everyone but Sylvester, it is obvious that the giant mouse is really a baby kangaroo.)

Silly, yes, but it is nonetheless an image that springs to mind when looking at the recent campuswide memo outlining the latest round of strategic projects that will be receiving funding from the estate of Lallage Feazel Wall: "Development of a State-of-the-Art Transgenic/Knockout Mouse Facility."

Knockout mice? Doesn't New Orleans have enough problems? But knockout mice are serious business, with a world of potential for human health. In a real sense, the new facility, which will be housed in the uptown vivarium in Stern Hall, will indeed result in a new strain of super-mice. But these "designer mice" will be helping Tulane scientists find ways to battle conditions such as Alzheimer's disease, cleft palates and heart defects.

The proposal for the facility, approved in May for Wall funding of $365,000 over three years as well as an enhancement grant from the Louisiana Board of Regents, was submitted by a team from across the university: George Flowers, associate professor and chair of geology, and faculty coordinator for the uptown vivarium and the Coordinated Instrumentation Facility; James Blanchard, senior veterinarian at the Tulane Primate Research Center; Yiping Chen, associate professor of cell and molecular biology; assistant professors of cell and molecular biology Bret Smith, Carol Burdsal and Liang Ma; Gary Hoyle, associate professor of pulmonary medicine and head of the lung research group at the health sciences center; and Prescott Deninger, associate director for research at the Tulane Cancer Center.

Transgenic and knockout mice, says Flowers, hold tremendous potential for the next generation of genetic medical research. Basically, scientists with the proper facilities--which the Wall funds will enable Tulane to have--are able to breed mice either with an extra gene for a specific disease or condition, or lacking a gene suspected of causing a specific disease or condition. The mice with the extra genes are transgenic; knockout mice are those lacking a specific gene.

"Scientists have mapped the human genome but we don't yet know exactly what each gene does," Flowers explains. "Suppose we had an idea that a certain gene created a protein required in the synthesis of insulin. We could go in, knock out that gene, and see if we can produce an insulin-deficient mouse."

Such specific genetic mapping would have enormous implications in the treatment and prevention of diabetes. Mice, Flowers says, are excellent models for understanding human genetic makeup. "Theirs is similar to our own genetic makeup," he notes.

Currently, Flowers says, faculty members interested in working in genetic research are hampered by the cost and waiting time involved in purchasing transgenic and knockout mice from the small number of facilities producing them commercially. A breeding pair of knockout mice for Alzheimer's research, for example, can cost as much as $500,000. The demand from the growing number of genetic researchers across the country means that the facilities producing the mice can only meet a portion of the demand, and can only produce mice that are more widely needed.

For Yiping Chen, one of whose research areas is studying the genes that control the growth of teeth, getting such specialized "designer mice" is next to impossible. Chen also is working on other projects promising great impact from the availability of knockout mice: study of the molecular basis of cleft palate formation, and identification of the genes that control heart position within the body.

"One of every 6,000 to 8,000 people are born with their hearts on the right side of the body," he explains, adding that this positioning has a great impact on the person's health and development. The Wall funds will enable Tulane to purchase and install autoclaving equipment and micro-isolator units to house the transgenic and knockout mice in the uptown vivarium, and will also allow the university to purchase equipment and supplies to create the designer mice.

This involves the detailed work of being able to add or remove genetic material at the embryonic stage of development, Chen says. With more ready access to the designer mice they need for specific projects, Flowers says, Tulane researchers will have a tremendous boost in competitiveness when it comes to obtaining external funding for biomedical research.

Tulane scientists are the only ones in Louisiana doing work with knockout mice, Chen notes, though research with transgenic mice is taking place elsewhere. Current plans call for the production of Tulane's first knockout mice in two years, Flowers says.

Tulane University, New Orleans, LA 70118 504-865-5000