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Hair Loss News Archives
November 2005
Stratifin gene defect leading to abnormal skin development and cancer identified
Nov 2005
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, at Thomas Jefferson University in
Philadelphia and at Jefferson's Kimmel Cancer Center and
Bruce Herron, at the Wadsworth Center of the New York State
Department of Health and 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 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.
The research team described in the journal Nature Genetics
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 repeated
epilation features," Herron sais. When the repeated
epilation mutation was "rescued" by providing a molecular
carrier containing normal genetic regions of chromosome 4,
the mice had normal hair development.
" We were interested in genes affecting susceptibility to
the development of skin cancer, and the repeated epilation
mice provided a good model," Siracusa said. The initial goal
of the work was to find out what gene was responsible for
the repeated epilation mutation.
" We think the mutation is potentially another player in
what could be a relatively novel pathway affecting the
development of hair and skin," Herron said. The Stratifin
gene is present in humans, and comparable genetic defects
are under investigation.
Siracusa and Herron's laboratories are continuing to
collaborate to understand the mechanisms behind the gene
defect's effects on skin development, 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 Stratifin gene could help lead to a better
understanding of the susceptibility to and development of
epithelial cancers such as those of the breast, prostate,
skin, lung, ovary and colon, and could predict a person's
response to cancer therapy. Further studies may also lead to
applications for hair loss treatment.
Source: Thomas Jefferson University, 2005