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Zebrafish teaches lessons about thrombosis — formation of clots

San Antonio (May 28, 2003) — In a laboratory full of fish tanks at The University of Texas Health Science Center at San Antonio, Pudur Jagadeeswaran, Ph.D., and his team are identifying gene defects that put the zebrafish at heightened risk for blood clots. Someday, the new assay they have developed may prove useful in preventing or at least diagnosing the estimated 700,000 strokes that occur each year in the United States. Stroke is the nation's third-leading killer and claims a new victim about every three minutes.

Because zebrafish are translucent, the researchers are able to videotape blood flow through veins and arteries and capture real-time footage of clot formation. By shining a laser beam through a fish that has a mutation due to exposure to a gene-harming agent — or else a reduced protein production caused by interruption of a gene's messenger RNA — the scientists can induce clots very quickly. "We measure the time it takes to form an occlusion of the vessel," said Dr. Jagadeeswaran, professor in the department of cellular and structural biology. "In a developing zebrafish only three millimeters in size, the clot generally forms in about 20 seconds. The hope is to identify genes with mutations that would result in shortening the occlusion time to less than 20 seconds. We believe these will prove to be the risk factor genes for thrombosis, which clogs the arteries. All the experiments could be done in a week. This speed of detection of genes makes the zebrafish an excellent model for fishing out genes."

The assay of the fish's genetic material helps the researchers correlate specific gene mutations with the time it takes the vessel to occlude. "Based on this assay, we have identified mutations that prompt vessel occlusion in less than 20 seconds, whereas other gene mutations extend occlusion past one minute," Dr. Jagadeeswaran said. "Both are important. We guess that 100 to 150 genes are related to clot formation, and half are yet to be discovered. Finding a mutation that shortens the time to occlusion will be very important as a model of stroke. Finding a mutation that lengthens the time to occlusion will be important in the study of hemophilia, a condition in which blood does not clot quickly enough."

The laser beam is delivered through a $50,000 laser generator coupled with a high-power microscope. The Health Science Center is one of the leading U.S. zebrafish study centers, along with Harvard University, the Massachusetts Institute of Technology, the Carnegie Institute in Washington, the University of San Francisco, Washington University in St. Louis and the University of Oregon. The Health Science Center is the only one studying thrombosis in the zebrafish model.

To see a video of clot formation in a zebrafish, go to http://www.uthscsa.edu/csb/faculty/jagadees.html and click on "laser-induced venous thrombosis."

Contact: Will Sansom