| Autor: |
Press E; Department of Physiology and Pharmacology, University of Western Ontario, London, ON, Canada., Alaga KC; Department of Anatomy and Cell Biology, University of Western Ontario, London, ON, Canada., Barr K; Department of Anatomy and Cell Biology, University of Western Ontario, London, ON, Canada., Shao Q; Department of Anatomy and Cell Biology, University of Western Ontario, London, ON, Canada., Bosen F; LIMES (Life and Medical Sciences Institute), Molecular Genetics, University of Bonn, Bonn, Germany., Willecke K; LIMES (Life and Medical Sciences Institute), Molecular Genetics, University of Bonn, Bonn, Germany., Laird DW; Department of Physiology and Pharmacology, University of Western Ontario, London, ON, Canada.; Department of Anatomy and Cell Biology, University of Western Ontario, London, ON, Canada. |
| Abstrakt: |
Several mutant mice have been generated to model connexin (Cx)-linked skin diseases; however, the role of connexins in skin maintenance and during wound healing remains to be fully elucidated. Here we generated a novel, viable, and fertile mouse (Cx26 CK14-S17F/+ ) with the keratitis-ichthyosis-deafness mutant (Cx26S17F) driven by the cytokeratin 14 promoter. This mutant mouse mirrors several Cx26-linked human skin pathologies suggesting that the etiology of Cx26-linked skin disease indeed stems from epidermal expression of the Cx26 mutant. Cx26 CK14-S17F/+ foot pad epidermis formed severe palmoplantar keratoderma, which expressed elevated levels of Cx26 and filaggrin. Primary keratinocytes isolated from Cx26 CK14-S17F/+ neonates exhibited reduced gap junctional intercellular communication and migration. Furthermore, Cx26 CK14-S17F/+ mouse skin wound closure was normal but repaired epidermis appeared hyperplastic with elevated expression of cytokeratin 6. Taken together, we suggest that the Cx26S17F mutant disturbs keratinocyte differentiation and epidermal remodeling following wound closure. We further posit that Cx26 contributes to epidermal homeostasis by regulating keratinocyte differentiation, and that mice harboring a disease-linked Cx26 mutant display epidermal abnormalities yet retain most wound healing properties. |
