Mice lacking desmocollin 1 show epidermal fragility accompanied by barrier defects and abnormal differentiation

M Chidgey, C Brakebusch, E Gustafsson… - The Journal of cell …, 2001 - rupress.org
M Chidgey, C Brakebusch, E Gustafsson, A Cruchley, C Hail, S Kirk, A Merritt, A North…
The Journal of cell biology, 2001rupress.org
The desmosomal cadherin desmocollin (Dsc) 1 is expressed in upper epidermis where
strong adhesion is required. To investigate its role in vivo, we have genetically engineered
mice with a targeted disruption in the Dsc1 gene. Soon after birth, null mice exhibit flaky skin
and a striking punctate epidermal barrier defect. The epidermis is fragile, and acantholysis in
the granular layer generates localized lesions, compromising skin barrier function.
Neutrophils accumulate in the lesions and further degrade the tissue, causing sloughing …
The desmosomal cadherin desmocollin (Dsc)1 is expressed in upper epidermis where strong adhesion is required. To investigate its role in vivo, we have genetically engineered mice with a targeted disruption in the Dsc1 gene. Soon after birth, null mice exhibit flaky skin and a striking punctate epidermal barrier defect. The epidermis is fragile, and acantholysis in the granular layer generates localized lesions, compromising skin barrier function. Neutrophils accumulate in the lesions and further degrade the tissue, causing sloughing (flaking) of lesional epidermis, but rapid wound healing prevents the formation of overt lesions. Null epidermis is hyperproliferative and overexpresses keratins 6 and 16, indicating abnormal differentiation. From 6 wk, null mice develop ulcerating lesions resembling chronic dermatitis. We speculate that ulceration occurs after acantholysis in the fragile epidermis because environmental insults are more stringent and wound healing is less rapid than in neonatal mice. This dermatitis is accompanied by localized hair loss associated with formation of utriculi and dermal cysts, denoting hair follicle degeneration. Possible resemblance of the lesions to human blistering diseases is discussed. These results show that Dsc1 is required for strong adhesion and barrier maintenance in epidermis and contributes to epidermal differentiation.
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