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Immune system protein may be critical in kidney disorders and other diseases

St. Louis, Oct. 8, 1999--Evolution has an uncanny way of reusing good blueprints, as researchers recently were reminded when they discovered that a protein involved in immune-cell interactions may be important for kidney function.

Andrey S. Shaw, M.D., principal investigator of the research on the CD2-associated protein, says, "Defects in CD2AP may play a critical role in some kidney diseases."

The research is published in today's issue of Science. The first authors of the paper are postdoctoral fellow Neng-Yao Shih, Ph.D., and research associate Jun Li, who both work in Shaw's laboratory at Washington University School of Medicine in St. Louis.

Shaw, associate professor of pathology, led a team of researchers who studied the protein. His group originally cloned the gene as a molecule important for T cell function. The researchers were surprised to find that CD2AP is also specifically expressed in the kidney glomerulus, which filters toxins and other substances from the blood.

The researchers found that mice lacking CD2AP had defective glomeruli and died of renal failure. When they analyzed these mice, they found that CD2AP was expressed in the kidney, mainly in a cell known as a glomerular epithelial cell. The glomerular epithelial cell has a complex shape with foot-like extensions that wrap around capillaries of the glomerulus, forming spaces for the flow of blood filtrate that are called slit diaphragms. In the mice lacking CD2AP, the epithelial cells were damaged and the slit diaphragms were lost.

The mice, developed by Shih and Li, died of kidney failure by the time they were 6 weeks old. The researchers, including co-author Jeffrey H. Miner, Ph.D., assistant professor of medicine and of cell biology and physiology, found progressive damage to the foot-like extensions as early as one week after the mice were born.

How could missing CD2AP have such a dramatic effect on the kidneys? To address this question, Shaw re
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Contact: Barbra Rodriguez
rodrigub@medicine.wustl.edu
314-286-0122
Washington University School of Medicine
8-Oct-1999


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