title: Cellular mechanisms of mutant connexins in skin disease and hearing loss.
abstract: It has been demonstrated that distinct germline mutations within four connexin (Cx) genes, Cx26, Cx30, Cx31, and Cx30.3, underlie hearing loss and/or epidermal disease. Here, we describe two Cx26 mutations associated with skin disease. With the goal of understanding the mechanism(s) of Cx-associated human disease and how different mutations within the same Cx protein can result in different disorders, we performed a number of functional analyses investigating the cellular effects of disease-associated Cx mutations in keratinocytes and other cell types. Epidermal disease-associated proteins studied were primarily cytoplasmic with limited trafficking ability. FACS analysis of WT and mutant EGFP-Cx31 transfected keratinocytes revealed a high percentage of cell death associated with the skin disease-associated mutant Cx31 proteins.
authors.affiliation: Centre for Cutaneous Research, Barts and the London School of Medicine and Dentistry, Queen Mary, University of London, Whitechapel, London, United Kingdom.
authors.forename: John E A
authors.initials: JE
authors.lastname: Common
authors.forename: Wei-Li
authors.initials: WL
authors.lastname: Di
authors.forename: Derek
authors.initials: D
authors.lastname: Davies
authors.forename: Helen
authors.initials: H
authors.lastname: Galvin
authors.forename: Irene M
authors.initials: IM
authors.lastname: Leigh
authors.forename: Edel A
authors.initials: EA
authors.lastname: O'Toole
authors.forename: David P
authors.initials: DP
authors.lastname: Kelsell
mesh_terms: D002478:Cells, Cultured; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics / Q000378:metabolism*; D017629:Gap Junctions / Q000235:genetics / Q000378:metabolism*; D049452:Green Fluorescent Proteins; D034381:Hearing Loss / Q000235:genetics; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism*; D008164:Luminescent Proteins / Q000378:metabolism; D009154:Mutation; D012871:Skin Diseases / Q000235:genetics*
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D008164:Luminescent Proteins; D000072259:Connexin 26; C068044:GJB3 protein, human; D049452:Green Fluorescent Proteins