Researchers at Jefferson Medical College and at the Wadsworth Center inNew York have identified a gene defect in mice resulting in a range ofabnormalities, from cyclical hair loss and skin cancer to severeproblems in normal skin development. The work may lead to improvedtreatments for skin injuries, including burns, and might haveimplications for diseases such as eczema and psoriasis, as well ascertain cancers.
Linda Siracusa, Ph.D., associate professor of microbiology andimmunology at Jefferson Medical College of Thomas Jefferson Universityin Philadelphia and at Jefferson's Kimmel Cancer Center and BruceHerron, Ph.D., a research scientist at the Wadsworth Center of the NewYork State Department of Health and assistant professor in theDepartment of Biomedical Sciences at the State University of New Yorkat Albany, wanted to identify the nature of an inherited geneticmutation in mice called repeated epilation (Er), and pinpoint the geneitself.
Mice carrying one copy of the mutation have cyclical hair loss, anddevelop skin cancer late in life. Mice carrying two copies have severedefects in skin development related to keratinocyte (skin cell)differentiation. At birth, they lack external openings -- the nose andmouth 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 researchteam describes how it subsequently narrowed the region on chromosome 4to about 800 megabases, eventually uncovering a mutation in a gene,Stratifin. Stratifin is highly expressed in the epidermis and plays arole in preventing human cancers. The researchers identified an"insertion" mutation in the gene that resulted in a damaged Stratifinprotein.
"We looked at a number of inbred strains and only saw a mutation in theStratifin gene in mice with the Er features," Dr. Herron says. When theEr mutation was "rescued" by providing a molecular carrier containingnormal genetic regions of chromosome 4, the mice had normal hairdevelopment.
"We were interested in genes affecting susceptibility to thedevelopment of skin cancer, and the Er mice provided a good model,"says Dr. Siracusa. The initial goal of the work was to find out whatgene was responsible for the Er mutation.
"We think the mutation is potentially another player in what could be arelatively novel pathway affecting the development of hair and skin,"says Dr. Herron. The Stratifin gene is present in humans, andcomparable genetic defects are under investigation.
Drs. Siracusa and Herron's laboratories are continuing to collaborateto understand the mechanisms behind the gene defect's effects on skindevelopment, hair growth and tumor development.
The researchers note that Stratifin is turned off in many cancers,suggesting it may protect cells from becoming cancerous. The Stratifingene could help lead to a better understanding of the susceptibility toand development of epithelial cancers such as those of the breast,prostate, skin, lung, ovary and colon, and could predict a person'sresponse to cancer therapy. Further studies may also lead toapplications for hair loss treatment.
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