p>Skin is an extremely important tissue, as it is the largest tissue in the body and it provides a critical external barrier. Normal epidermis has four layers of keratinocytes. The UI study showed that mice that lack IRF6 have abnormal skin development and are missing the upper two cellular layers of the epidermis. The researchers also showed abnormal proliferation of keratinocytes in one of the remaining two layers and failure of these cells to die off or differentiate as normal.

Although humans with Van der Woude syndrome do not have skin defects, a similar human condition, called popliteal ptyergium syndrome (PPS) that is also caused by mutations in IRF6, does cause skin abnormalities in addition to cleft lip and palate. Thus, the UI researchers were not completely surprised by the skin abnormalities in the mice.

Mice provided a particularly good animal model for the UI study because mice and humans have very similar facial development and both share the distinctive mammalian structure of a palate, which separates the nasal airway from the mouth allowing a baby to suckle. In addition, it is fairly easy to create mutations in mice to study a particular gene's function.

"Having an animal model for a major human birth defect like cleft lip and palate provides us with the opportunity to investigate ways to better treat and prevent these disorders much more quickly than was previously possible," Murray said. "Dr. Schutte's work has also expanded our knowledge of other critical areas of human health such as the role of our skin in development and in how wounds and scars may heal."

"Our results open many new avenues of research because the function we discovered for IRF6 is vastly different than the best understood function for the other IRF genes," Schutte added.

IRF6 belongs to a family of nine IRF genes, which have been extensively investigated. The UI study reveals that IRF6 has a different function than the other known
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Contact: Dave Pedersen
david-pedersen@uiowa.edu
319-335-8032
University of Iowa
15-Oct-2006

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