title: A mouse keratin 1 mutation causes dark skin and epidermolytic hyperkeratosis.
abstract: Chemical mutagenesis in the mouse has increased the utility of phenotype-driven genetics as a means for studying different organ systems, developmental pathways, and pathologic processes. From a large-scale screen for dominant phenotypes in mice, a novel class of pigmentation mutants was identified by dark skin (Dsk). We describe a Dsk mutant, Dsk12, which models the human disease, epidermolytic hyperkeratosis (EHK). At 2 days of age, mutant animals exhibit intraepidermal blisters and erosions at sites of trauma, and by 2 weeks of age develop significant hyperkeratosis. We identified a missense mutation in mutant animals that predicts an S194P amino acid substitution in the 1A domain of Keratin 1, a known target for human mutations that cause EHK. Dsk12 recapitulates the gross pathologic, histologic, and genetic aspects of the human disorder, EHK.
authors.affiliation: Departments of Genetics, Stanford University School of Medicine, Beckman Center B281, Stanford, CA 94305-5323, USA. kelly.mcgowan@yahoo.com
authors.forename: Kelly A
authors.initials: KA
authors.lastname: McGowan
authors.forename: Swaroop
authors.initials: S
authors.lastname: Aradhya
authors.forename: Helmut
authors.initials: H
authors.lastname: Fuchs
authors.forename: Martin H
authors.initials: MH
authors.lastname: de Angelis
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Barsh
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D017488:Hyperkeratosis, Epidermolytic / Q000209:etiology* / Q000235:genetics; D007633:Keratins / Q000235:genetics*; D051379:Mice; D008809:Mice, Inbred C3H; D020125:Mutation, Missense; D012880:Skin Pigmentation
chemical_list: D007633:Keratins