title: The effects of a mutant connexin 26 on epidermal differentiation.
abstract: To elucidate the mode of action of dominant mutant connexins in causing inherited skin diseases, transgenic mice were produced that express the true Vohwinkel syndrome-associated mutant Cx26 (D66H), from a keratin 10 promoter, specifically in the suprabasal epidermal keratinocytes. Following birth, the transgenic mice developed keratoderma similar to that of human carriers of Cx26 (D66H). Expression of the transgene resulted in a loss of Cx26 and Cx30 at intercellular junctions of epidermal keratinocytes and accumulation of these connexins in the cytoplasm. Injection of primary mouse keratinocytes with Lucifer Yellow showed no difference in terms of dye spreading between transgenic and non transgenic keratinocytes in vitro. Expression of the mutant Cx26 (D66H) did not interfere with the formation of the epidermal water barrier during late embryonic development. Attempts to produce transgenic mice expressing the wild type form of Cx26 from the K10 promoter failed to produce viable animals although transgenic embryos were recovered at days 9 and 12 of gestation, suggesting that the transgene might be embryonic lethal.
authors.affiliation: Division of Cancer Sciences and Molecular Pathology, University of Glasgow, Glasgow, Scotland, United Kingdom. gb99k@clinmed.gla.ac.uk
authors.forename: George
authors.initials: G
authors.lastname: Bakirtzis
authors.forename: Susan
authors.initials: S
authors.lastname: Jamieson
authors.forename: Trond
authors.initials: T
authors.lastname: Aasen
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; D002450:Cell Communication / Q000235:genetics / Q000502:physiology*; D000072259:Connexin 26; D000075302:Connexin 30; D017630:Connexins / Q000235:genetics / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000378:metabolism; D004817:Epidermis / Q000196:embryology / Q000378:metabolism*; D005799:Genes, Dominant; D007546:Isoquinolines / Q000737:chemistry; D015603:Keratinocytes / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic / Q000235:genetics
chemical_list: D000075302:Connexin 30; D017630:Connexins; C000607042:GJB2 protein, human; C491020:GJB6 protein, human; C000607043:Gjb2 protein, mouse; C100629:Gjb6 protein, mouse; D007546:Isoquinolines; D000072259:Connexin 26; C017475:lucifer yellow