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: Kelly A McGowan, Helmut Fuchs, Martin Hrabé de Angelis, Gregory S Barsh
• Journal: The Journal of investigative dermatology (J Invest Dermatol) Vol. 127 Issue 1 Pg. 60-4 (Jan 2007) ISSN: 1523-1747 [Electronic] United States
• PMID: 16858417 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Keratin-4

Topics

• Animals
• Disease Models, Animal
• Hair Color (genetics)
• Hamartoma (genetics)
• Keratin-4 (genetics)
• Leukoplakia, Oral (genetics)
• Mice
• Mice, Inbred C3H
• Mice, Inbred C57BL
• Mouth Diseases (genetics)
• Mouth Mucosa (pathology)
• Mutation, Missense