Abstract

Desmocollin 3 (DSC3) belongs to a subfamily of cadherins and is a major component of desmosomes in keratinocytes of stratified epithelia, such as the epidermis. Based on its amino acid sequence homology to classical cadherins, such as E-cadherin, it has been postulated that DSC3 functions as a cell-adhesion molecule. To test this hypothesis, we assessed the function of DSC3 in the development and maintenance of stratified epithelia, in particular the epidermis and hair follicles. Using a conditional null allele, we show that loss of Dsc3 function in the epidermis causes impaired cell-cell adhesion, leading to intra-epidermal blistering and telogen hair loss. Furthermore, the lesions in Dsc3-null skin resemble those observed in individuals with pemphigus vulgaris (PV), indicating that impaired Dsc3 function could be a potential cause of PV-like inherited or acquired skin blistering diseases.

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