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This one is about: Broken Gene Circuit May Cause Cleft Palate

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The following is a study that came out at year end:

Broken Gene Circuit May Cause Cleft Palate

NEW YORK (Reuters) -- A circuit of genes, when broken by exposure to steroid hormones during pregnancy, causes cleft palate in newborn mice, a new study shows.

The findings by researchers at the University of Southern California in Los Angeles may lead to a better understanding of how cleft palate occurs in humans.

The study results also add to the evidence for a link between the congenital disorder and exposure during pregnancy to risk factors that raise steroid levels in the body, such as smoking, stress, and certain medications.

"These risk factors have previously been identified by other researchers," says Dr. Michael Melnick, professor of genetics and director of the university's laboratory of developmental genetics. He says studying complex disorders like cleft palate and simply looking for genetic differences between healthy and affected individuals is not enough to explain the underlying causes of the disorder.

Melnick and his colleagues are studying two experimental strains of mice -- one strain bred to have offspring with cleft palate if exposed to steroids during pregnancy; the other strain resistant to steroid-induced cleft palate.

So far, the researchers have identified a circuit of at least three genes and their products that play key roles in the disorder: the genes for the growth factor receptor IGF-IIR, the growth factor TGF-beta2, and Cdk4, a protein that occurs with cell division. In mice susceptible to steroid-induced cleft palate, IGF-IIR is hyperactive, and steroids added to the circuit apparently make the gene even more so. This situation alters the function of other parts of the circuit so that normal palate development is affected, leaving a cleft in the roof of the mouth.

Cleft palate is a common congenital disorder in humans, affecting 1 in 2000 newborns. Melnick says molecules equivalent to those his team is studying are present in humans and that a similar genetic circuit may be involved in cleft palate. But he cautions that the situation in people may be more complicated.

"There are several tissues involved in forming the palate and they are under the direction of dozens of genes," the researcher says. "There are many potential places for things to go wrong, and the places may vary among families and racial groups." He sees his finding as offering "some promising targets to focus on" in human studies.

The study is published in the January issue of the journal Developmental Dynamics.

Reut13:55 12-30-97

(30 Dec 1997 13:54 EST)

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