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Jefferson scientists identify gene defect leading to abnormal skin development and cancer

Researchers at Jefferson Medical College and at the Wadsworth Center in New York have identified a gene defect in mice resulting in a range of abnormalities, from cyclical hair loss and skin cancer to severe problems in normal skin development. The work may lead to improved treatments for skin injuries, including burns, and might have implications for diseases such as eczema and psoriasis, as well as certain cancers.

Linda Siracusa, Ph.D., associate professor of microbiology and immunology at Jefferson Medical College of Thomas Jefferson University in Philadelphia and at Jefferson's Kimmel Cancer Center and Bruce Herron, Ph.D., a research scientist at the Wadsworth Center of the New York State Department of Health and assistant professor in the Department of Biomedical Sciences at the State University of New York at Albany, wanted to identify the nature of an inherited genetic mutation in mice called repeated epilation (Er), and pinpoint the gene itself.

Mice carrying one copy of the mutation have cyclical hair loss, and develop skin cancer late in life. Mice carrying two copies have severe defects in skin development related to keratinocyte (skin cell) differentiation. At birth, they lack external openings the nose and mouth are covered by skin, for example and live only a brief time.

Previous studies had pinned the gene's location to mouse chromosome 4. Reporting October 2, 2005 in the journal Nature Genetics, the research team describes how it subsequently narrowed the region on chromosome 4 to about 800 megabases, eventually uncovering a mutation in a gene, Stratifin. Stratifin is highly expressed in the epidermis and plays a role in preventing human cancers. The researchers identified an "insertion" mutation in the gene that resulted in a damaged Stratifin protein.

"We looked at a number of inbred strains and only saw a mutation in the Stratifin gene in mice with the Er features," Dr. Herron says. When the Er mutation was "rescued" by
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2-Oct-2005


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