January 26, 2001
Volume XXXIV, No. 4

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UTHSC scientists develop first zebra fish model of clotting

Scientists are reeling in a "big one" information on blood-clotting disorders with help from a species of fish that contains 70 percent of the same genes found in people.


Dr. Ravikumar Hanumanthaiah (left), a postdoctoral fellow in the department of cellular and structural biology, and Ph.D. student Michael Gregory are part of the UTHSC research team studying normal and abnormal coagulation in zebra fish models. The scientists work in Dr. Pudur Jagadeeswaran's laboratory.
Health Science Center researchers are the first to focus on blood clotting in varieties of zebra fish, which have a life span of 3 1/2 years and are the length of a thumbnail. The San Antonio team is able to observe normal circulation of blood and formation of clots in the fish. Basic research of the body's clotting mechanisms is crucial to development of human therapies for stroke, hemophilia and other clot-related disorders.

"Of the estimated 50,000 genes in the human body, 35,000 are found in the zebra fish," said Dr. Pudur Jagadeeswaran, associate professor in the department of cellular and structural biology and leader of the zebra fish project. "Our goal is to identify novel genes that play a role in clotting diseases, and we have developed fish with several different mutations in the genes controlling clotting."

The zebra fish research is supported by a four-year, $860,000 grant from the National Heart, Lung and Blood Institute.

The scientists published a paper detailing the three-dimensional structure of zebra fish prothombin, one of the coagulation factors. They also developed a sensitive test to overcome the technical difficulties of screening zebra fish for clotting defects. "This is a beautiful screening tool and no one else in the world has it," Dr. Jagadeeswaran said.

Hundreds of zebra fish are bred to show varying symptoms of abnormal internal clotting (called thrombosis), said Dr. Jagadeeswaran. Because the zebra fish embryo is nearly transparent, the scientists see changes as they occur. Michael Gregory, a Ph.D. candidate working with the team, has captured video of a clot forming in a localized area.

This disease model is easier to manipulate and less expensive to maintain than other laboratory models such as rodents, and yields as much information about disease pathology, Dr. Jagadeeswaran said. A handful of academic health science centers nationwide, including UTHSC, are establishing zebra fish resource laboratories. Ear defects, circadian rhythms, pigmentation patterns and eating disorders are interesting areas under study at other centers.

Nearly 60 million Americans have some form of cardiovascular disease, according to the American Heart Association, and clot formation is a threat to many. "Since so many suffer and die from these diseases, any new mechanism to understand them is an important advance," Dr. Jagadeeswaran said. cutline: Dr. Ravikumar Hanumanthaiah (left), a postdoctoral fellow in the department of cellular and structural biology, and Ph.D. student Michael Gregory are part of the UTHSC research team studying normal and abnormal coagulation in zebra fish models. The scientists work in Dr. Pudur Jagadeeswaran's laboratory.