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Gene Involved In Common Birth Defect Also Regulates Skin Biology

Following up on an earlier discovery that a gene called IRF6 is involved in the common birth defect cleft lip and palate, researchers at the University of Iowa Roy J. and// Lucille A. Carver College of Medicine and their colleagues have identified the function of the gene. Their latest findings, published online Oct. 15 in Nature Genetics, reveal an unexpected role for IRF6 in the growth and development of skin cells, a discovery that may have implications for wound healing and cancer research.

In 2002, Brian Schutte, Ph.D., UI associate professor of pediatrics and nursing, and Jeff Murray, M.D., UI professor of pediatrics, pediatric dentistry and biological sciences, and the Roy J. Carver Chair in Perinatal Health, led a study showing that mutations in IRF6 cause Van der Woude syndrome (VWS), a rare, dominantly inherited form of cleft lip and palate. Subsequently, the researchers found that this gene also is mutated in 10 to 15 percent of the more common, so-called non-syndromic cases of cleft lip and palate. Cleft lip and palate, where the lip or both the lip and palate (roof of the mouth) fail to close, occurs in approximately one of every 1,000 babies.

In order to determine the function of this gene, the researchers created mice that lacked IRF6. These mice had very abnormal skin as well as a cleft palate. Detailed analysis of the mice revealed that IRF6 regulates the proliferation and differentiation of keratinocytes -- the main cell type in the epidermis or outer layer of skin. Keratinocytes also provide a protective barrier around the mouth, gut, liver, lung, kidney and other internal organs.

'This study really looks at the role of IRF6 in skin development. By focusing on skin we felt we could learn more about this specific cell type that is also abnormal in the palate,' Schutte said. 'The insight we gained into the function of IRF6 will help focus research efforts to identify other genes involved in cleft lip and palate.'
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