dermatitis and aging-related barrier dysfunction in transgenic mice overexpressing an epidermal-targeted claudin 6 tail deletion mutant皮炎和体内屏障功能障碍在转基因小鼠overexpressing epidermal-targeted claudin 6尾缺失突变体.pdfVIP

Dermatitis and Aging-Related Barrier Dysfunction in Transgenic Mice Overexpressing an Epidermal-Targeted Claudin 6 Tail Deletion Mutant 1 1,2 ` 1,2 1,2 Tammy-Claire Troy , Azadeh Arabzadeh , Nathalie M.K. Lariviere , Adebola Enikanolaiye , Kursad Turksen1,2,3,4* 1 Sprott Centre for Stem Cell Research at the Ottawa Hospital Research Institute, Ottawa, Ontario, Canada, 2 Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada, 3 Divisions of Dermatology and Endocrinology, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada, 4 Division of Reproductive Endocrinology, Department of Obstetrics, Gynaecology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada Abstract The barrier function of the skin protects the mammalian body against infection, dehydration, UV irradiation and temperature fluctuation. Barrier function is reduced with the skin’s intrinsic aging process, however the molecular mechanisms involved are unknown. We previously demonstrated that Claudin (Cldn)-containing tight junctions (TJs) are essential in the development of the epidermis and that transgenic mice overexpressing Cldn6 in the suprabasal layers of the epidermis undergo a perturbed terminal differentiation program characterized in part by reduced barrier function. To dissect further the mechanisms by which Cldn6 acts during epithelial differentiation, we overexpressed a Cldn6 cytoplasmic tail deletion mutant in the suprabasal compartment of the transgenic mouse epidermis. Although there were no gross phenotypic abnormalities at birth, subtle epidermal anomali