Loss of desmocollin 3 in mice leads to epidermal blistering.
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.
Chen
Jiangli
J
Department of Dermatology, Charles C. Gates Regenerative Medicine and Stem Cell Biology Program, University of Colorado Denver, Aurora, CO 80045, USA.
Den
Zhining
Z
Koch
Peter J
PJ
D000818:Animals; D000831:Animals, Newborn; D001768:Blister / Q000473:pathology*; D002448:Cell Adhesion; D051187:Desmocollins; D003896:Desmosomes / Q000648:ultrastructure; D004817:Epidermis / Q000473:pathology* / Q000648:ultrastructure; D017353:Gene Deletion; D018390:Gene Targeting; D006197:Hair / Q000473:pathology; D019426:Integrases / Q000378:metabolism; D015603:Keratinocytes / Q000473:pathology / Q000648:ultrastructure; D008562:Membrane Glycoproteins / Q000172:deficiency* / Q000378:metabolism; D051379:Mice; D010641:Phenotype
D051187:Desmocollins; D008562:Membrane Glycoproteins; C090171:Dsc3 protein, mouse; C045073:Cre recombinase; D019426:Integrases