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Updated: Aug 7, 2026
Cell Population Analyses During Skin Carcinogenesis
Published on: August 21, 2013
Identification of a Keratin 4 mutation in a chemically induced mouse mutant that models white sponge nevus
Kelly A McGowan1, Helmut Fuchs, Martin Hrabé de Angelis
1Department of Genetics, Stanford University School of Medicine, Stanford, California 94305-5323, USA. kelly.mcgowan@yahoo.com
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.
Insights
A mouse model for white sponge nevus (WSN) was developed through chemical mutagenesis. This Bright coat color 1 (Bcc1) mutant exhibits skin defects and a keratin 4 mutation, mirroring the human genetic disorder.
Area of Science:
- Genetics
- Dermatology
- Animal Models
Background:
- Systematic chemical mutagenesis in mice aims to identify new genetic entry points for studying physiology and disease.
- Mouse mutants with inherited defects in skin and hair color are being studied to understand related genetic disorders.
Purpose of the Study:
- To describe a novel mouse mutant, Bright coat color 1 (Bcc1), with coat color changes and associated health defects.
- To investigate the genetic basis of Bcc1 and its potential as a model for human diseases.
Main Methods:
- Chemical mutagenesis in mice to generate mutations.
- Phenotypic analysis of coat color, skin, and oral tissues in mutant mice.
- Genetic sequencing to identify the causative mutation in the Bcc1 mutant.
Main Results:
- The Bcc1 mutant displays light-colored hair by 4 weeks of age.
- Homozygous Bcc1 mutants exhibit oral leukoplakia, blistering, and growth retardation.
- A missense mutation in the Keratin 4 (Krt2-4) gene, specifically an N154S substitution in the 1A domain, was identified in Bcc1 animals.
Conclusions:
- The identified mutation in Krt2-4 is homologous to mutations found in human white sponge nevus (WSN).
- The Bcc1 mouse mutant serves as a valuable model, recapitulating the pathologic, histologic, and genetic features of human WSN.
