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

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. S oon after birth, null mice exhibit flaky skin and a striking punctate epide rmal barrier defect. The epidermis is fragile, and acantholysis in the gran ular layer generates localized lesions, compromising skin barrier function. Neutrophils accumulate in the lesions and further degrade the tissue, caus ing sloughing (flaking) of lesional epidermis, but rapid wound healing prev ents the formation of overt lesions. Null epidermis is hyperproliferative a nd overexpresses keratins 6 and 16, indicating abnormal differentiation. Fr om 6 wk, null mice develop ulcerating lesions resembling chronic dermatitis . We speculate that ulceration occurs after acantholysis in the fragile epi dermis because environmental insults are more stringent and wound healing i s less rapid than in neonatal mice. This dermatitis is accompanied by local ized hair loss associated with formation of utriculi and dermal cysts, deno ting hair follicle degeneration. Possible resemblance of the lesions to hum an blistering diseases is discussed. These results show that Dsc1 is requir ed for strong adhesion and barrier maintenance in epidermis and contributes to epidermal differentiation.