Scientists at the University of Southern California have identified a genetic circuit that when broken causes cleft palate in newborn mice, according to a story in Dentistry Today.
The critical points of the circuit represent genes and gene products that interact with each other to direct palate formation. The surge that caused the circuit to break in the mice was an environmental assault in the form of steroid hormones given to female mice during pregnancy.
According to the study, which was partly supported by the National Institute of Dental Research, this is the first time a cause-and-effect scenario for cleft palate has been worked out at the molecular level.
The findings may help define the genetic components of cleft palate in humans and explain the link of risk factors such as stress, smoking and certain medications that are known to elevate the level of steroids in the body.
"Facial clefting disorders are among the most common human birth defects and occur in almost one in 2,000 live births," says Dr. Tina Jaskoll, one of the study's principal investigators. "The defects can range in severity from a relatively minor split uvula at the rear of the mouth to a cleft running the length of the hard and soft tissues forming the roof of the mouth."
The more severe forms require surgery and are often associated with psychological and physical problems, she added.
The investigators believe cleft palate results from a combination of genetic and environmental factors, but attempts to identify these components in human populations have proved inconclusive to this point.
Dr. Michael Melnick, another of the study's principal investigators, believes the mouse model used in his team's study will provide the clues needed to unravel the mysteries of cleft palate.
Currently, he cautioned, it is still premature to pinpoint the underlying causes of cleft palate in humans.
"It is apparent from studying complex disorders, such as cleft palate, that simply identifying genetic differences between healthy and affected individuals is not enough to explain the cause of the disorder," says Dr. Melnick. "We must know what products are derived from the genes in question and what other genes and molecules are affected in the chain of events that lead to the formation of the palate."
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