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Genes That Locate Organs Found

November 2, 1997

NEW YORK (AP) _ Researchers have found two of the genes that help the developing embryo tell left from right when deciding where to put the internal organs.

The heart, stomach and spleen normally end up on the left side of the body, the liver on the right. That placement is almost always determined within a few weeks of conception, when a series of biochemical events tells the developing embryo which side is which.

But one time in 10,000, in a condition known as heterotaxy, the embryo never distinguishes left from right. The organs end up in the wrong orientation, and serious medical problems can result. People with heterotaxy rarely live past young adulthood.

Biologists now know of two genes that can cause heterotaxy, one in humans and one in mice. Mutations in the human gene, ZIC3, have been found in four families with members who have heterotaxy. And mutations in another gene, lrd, can cause heterotaxy in mice.

``Until now there hasn’t been any genetic or molecular understanding of what’s going on here,″ said Brett Casey, an assistant professor of pathology at the Baylor College of Medicine in Houston.

Although heterotaxy will never be cured, he said, a number of treatments can be developed if the genetic causes of the disorder are better understood.

With colleagues from Missouri, North Carolina, California, Britain and Canada, Casey discovered that the ZIC3 gene acts as a sort of master switch, turning on a cascade of biochemical processes that put the organs in their proper places.

Meanwhile the mouse gene, described in the Oct. 30 issue of the journal Nature by researchers from Cincinnati and Connecticut, codes for a protein that may be part of the biochemical cascade that ZIC3 sets off. The mouse protein, left-right dynein, is a cellular motor that moves things inside cells. Humans also have a version of left-right dynein.

Nobody knows yet what the dynein is moving, or whether its production is actually stimulated by ZIC3. In fact, precious little is known about any aspect of how embryos tell left from right.

``These are things we’re just beginning to look at,″ said Dorothy Supp, a researcher who contributed to the research while at Children’s Hospital in Cincinnati.

She and her colleagues hope that further work will reveal the chain of events that must occur for the organs to be properly arranged.

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