title: Targeted epidermal expression of mutant Connexin 26(D66H) mimics true Vohwinkel syndrome and provides a model for the pathogenesis of dominant connexin disorders.
abstract: To investigate the role of connexins in dominantly inherited skin disease, transgenic mice were produced which expressed mutant connexin 26 [gjb2/connexin 26(D66H)], from a keratin 10 promoter, exclusively in the suprabasal epidermis (the cells in which Connexin 26 is up-regulated in epidermal hyperproliferative states). From soon after birth, the mice exhibited a keratoderma similar to that in humans carrying the Connexin 26(D66H) mutation (true Vohwinkel syndrome). Transgene expression was associated with loss of Connexin 26 and Connexin 30 from epidermal keratinocyte intercellular junctions and accumulation in cytoplasm. Light and electron microscopy showed marked thickening of the epidermal cornified layers and increased epidermal TUNEL staining, indicative of premature keratinocyte programmed cell death. The K10Connexin 26(D66H) mouse may provide a valuable model to study the role of gap-junctional intercellular communication in epidermal differentiation. Similarities in phenotype between individuals (man and mouse) carrying Connexin 26(D66H) and those carrying insertional mutants of Loricrin, a major cornified envelope protein of the epidermis, suggest a possible link between connexin function and cornified envelope formation.
authors.affiliation: Section of Squamous Cell Biology and Dermatology, Division of Cancer Sciences and Molecular Pathology, Robertson Building, University of Glasgow, Glasgow G12 8QQ, Scotland, UK.
authors.forename: George
authors.initials: G
authors.lastname: Bakirtzis
authors.forename: Rukhsana
authors.initials: R
authors.lastname: Choudhry
authors.forename: Trond
authors.initials: T
authors.lastname: Aasen
authors.forename: Leonard
authors.initials: L
authors.lastname: Shore
authors.forename: Ken
authors.initials: K
authors.lastname: Brown
authors.forename: Sheila
authors.initials: S
authors.lastname: Bryson
authors.forename: Stephen
authors.initials: S
authors.lastname: Forrow
authors.forename: Laurence
authors.initials: L
authors.lastname: Tetley
authors.forename: Malcolm
authors.initials: M
authors.lastname: Finbow
authors.forename: David
authors.initials: D
authors.lastname: Greenhalgh
authors.forename: Malcolm
authors.initials: M
authors.lastname: Hodgins
mesh_terms: D000818:Animals; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics* / Q000378:metabolism; D004817:Epidermis / Q000378:metabolism*; D005799:Genes, Dominant; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D012868:Skin Abnormalities / Q000235:genetics*
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; C000607043:Gjb2 protein, mouse; D000072259:Connexin 26