The co-repressor hairless has a role in
epithelial cell differentiation in the skin.
Zarach JM, Beaudoin III GM, Coulombe PA, Thompson CC.2004 Jul
Although mutations in the mammalian hairless (Hr) gene result in
congenital hair loss disorders in both mice and humans, the precise role
of Hr in skin biology remains unknown.
We have shown that the protein encoded by Hr (HR) functions as a
nuclear receptor co-repressor.
To address the role of HR in vivo, we generated a loss-of-function
(Hr(-/-)) mouse model. The Hr(-/-) phenotype includes both hair loss and
severe wrinkling of the skin.
Wrinkling is correlated with increased cell proliferation in the
epidermis and the presence of dermal cysts. In addition, a normally
undifferentiated region, the infundibulum, is transformed into a
morphologically distinct structure (utricle) that maintains epidermal
function.
Analysis of gene expression revealed upregulation of keratinocyte
terminal differentiation markers and a novel caspase in Hr(-/-) skin,
substantiating HR action as a co-repressor in vivo.
Differences in gene expression occur prior to morphological changes
in vivo, as well as in cultured keratinocytes, indicating that aberrant
transcriptional regulation contributes to the Hr(-/-) phenotype.
The properties of the cell types present in Hr(-/-) skin suggest that
the normal balance of cell proliferation and differentiation is
disrupted, supporting a model in which HR regulates the timing of
epithelial cell differentiation in both the epidermis and hair follicle.
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