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A spontaneous mouse hair mutation was identified in a C3H/HeN colony. The mode of inheritance of the mutation was semidominant, with incomplete penetrance when heterozygous. The trait is controlled by a single locus hague (Hag), which was mapped to the telomeric region of chromosome 15. This mutation was shown to be unstable, since its transmission could be switched from semidominant to recessive. To identify the causative gene and the nature of the mutation, hague was introduced into a high-resolution and high-density molecular genetic map. Over 2000 meioses were analyzed and the mutation was mapped to the keratin 2 complex genes. A YAC and BAC physical map of the critical region was then constructed and the gene involved was located in a 600- to 800-kb-long segment. Fourteen genes were mapped to this region; of these, 11 were expressed in the skin (5 epidermic cytokeratin and 6 hard keratin genes), but none were mutated in hague mice.

Hague (Hag): A New Mouse Hair Mutation With an Unstable Semidominant Allele