GENETIC CHARACTERIZATION OF THE HYPOTRICHOTIC MUTATION

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DESCRIPTION: A spontaneous hypotrichotic mutant, characterized by the partial or complete absence of hair over most of the body, was discovered in Dr. King's colony of albino laboratory rats. Preliminary data demonstrate that the trait is inherited as an autosomal recessive gene, provisionally named shorn (shn), that is not allelic with any of the other known hypotrichotic mutations in rats. Shn maps to rat Chromosome (Chr) 10, which, excepting rnu, does not include any other named loci that are known to affect coat morphology. Homologous regions of the mouse genome also lack loci that are known to cause recessive hypotrichosis. The shn mutation therefore appears to identify a new gene that is essential for the normal development or maintenance of mammalian skin and hair. To advance the understanding of the shn gene's normal role in development, Dr. King proposes to characterize the shn mutation both genotypically and phenotypically. At the genotypic level of investigation, he aims to produce a fine-structure genetic map of the region around shn. Toward this aim, he will conduct a backcross of shn/+ F1 rats that are heterozygous for a large number of visible, biochemical, and PCR-scorable DNA markers. Analysis of about 250 progeny from this backcross will allow generation of a high-resolution, high-density genetic map of the region including and surrounding shn. This fine-structure genetic map, while advancing the genetic characterization of a 20-30 cM region of the rat genome, will facilitate identification of probes and candidates for the shn gene. At the phenotypic level, he proposes to carry out biochemical and histological comparisons between mutant and non-mutant testcross siblings. The biochemical analysis will focus on gene products known to be controlled by loci mapping in the same region as shn. Histological analysis of skin and other tissues may reveal pleiotropic effects of the mutation, and could help to implicate particular cell types, biomolecules, or a particular time or process involved in the development of the mutant phenotype. The genotypic and phenotypic investigations are expected to result in the identification of the shn gene, which in turn could lead to studies on its role in the normal development of mammalian skin and hair.