title: Identification of a Keratin 4 mutation in a chemically induced mouse mutant that models white sponge nevus.
abstract: With the goal of increasing the number of genetic entry points for studying physiologic processes and human disease, large-scale, systematic, chemical mutagenesis projects in mice have been initiated in several different centers. We have been studying mouse mutants that exhibit dominantly inherited defects in either skin and/or hair color. Here, we describe a bright coat color mutant, Bright coat color 1 (Bcc1), which develops light-colored hair at 4 weeks of age, and when homozygous exhibits oral leukoplakia and blistering, and growth retardation. We identified a missense mutation in mutant animals that predicts an N154S amino-acid substitution in the 1A domain of Keratin 4 (encoded by the Krt2-4 gene), a region known to be mutated in human patients with white sponge nevus (WSN). Bcc1 recapitulates the gross pathologic, histologic, and genetic aspects of the human disorder, WSN.
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, California 94305-5323, USA. kelly.mcgowan@yahoo.com
authors.forename: Kelly A
authors.initials: KA
authors.lastname: McGowan
authors.forename: Helmut
authors.initials: H
authors.lastname: Fuchs
authors.forename: Martin
authors.initials: M
authors.lastname: Hrabé de Angelis
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Barsh
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006200:Hair Color / Q000235:genetics; D006222:Hamartoma / Q000235:genetics*; D053527:Keratin-4 / Q000235:genetics*; D007972:Leukoplakia, Oral / Q000235:genetics*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009059:Mouth Diseases / Q000235:genetics*; D009061:Mouth Mucosa / Q000473:pathology; D020125:Mutation, Missense
chemical_list: D053527:Keratin-4