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: Kelly A McGowan, Swaroop Aradhya, Helmut Fuchs, Martin H de Angelis, Gregory S Barsh
• Journal: The Journal of investigative dermatology (J Invest Dermatol) Vol. 126 Issue 5 Pg. 1013-6 (May 2006) ISSN: 0022-202X [Print] United States
• PMID: 16528356 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Keratins

Topics

• Animals
• Disease Models, Animal
• Hyperkeratosis, Epidermolytic (etiology, genetics)
• Keratins (genetics)
• Mice
• Mice, Inbred C3H
• Mutation, Missense
• Skin Pigmentation