Cellular mechanisms of mutant connexins in skin disease and hearing loss.
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.
Common
John E A
JE
Centre for Cutaneous Research, Barts and the London School of Medicine and Dentistry, Queen Mary, University of London, Whitechapel, London, United Kingdom.
Di
Wei-Li
WL
Davies
Derek
D
Galvin
Helen
H
Leigh
Irene M
IM
O'Toole
Edel A
EA
Kelsell
David P
DP
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*
D017630:Connexins; C000607042:GJB2 protein, human; D008164:Luminescent Proteins; D000072259:Connexin 26; C068044:GJB3 protein, human; D049452:Green Fluorescent Proteins