Positional cloning of mutations that disrupt hair development in mice.

Central Connecticut State University, New Britain CT

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Abstract

DESCRIPTION (provided by applicant): The mammalian integument offers a particularly valuable system for the genetic analysis of development. Mutations that affect hair and skin formation or maintenance are readily detected by simple visual screens, and such variants generally show good viability. Also, the late development of a hairy coat (largely after parturition) and its location on the outside of the body allow easy access to developing mutant and wild type tissues. While we believe that skin and hair variants can, in these ways, provide a unique insight into the genetic control of mammalian development, it is clear that only the molecular-genetic assignment of each mutant trait will allow investigation of the altered processes to proceed. Therefore, to advance such investigations, we propose to identify (by a positional-cloning approach) the genes that are disrupted in a set of recessive mutations that cause defective hair and skin development in mice, including: juvenile alopecia (jal), wooly (wly), frizzy-like (frzl), retarded hair growth (rhg), follicular dystrophy (fold), and wellhaarig (we). These studies also promise to enhance research activity at CCSU by providing undergraduate and master's-level students with a variety of defined projects focused on the molecular assignment and further characterization of this set of poorly understood genetic variants. PUBLIC HEALTH RELEVANCE: These investigations promise to enhance research activity at Central Connecticut State University while advancing the molecular characterization of several mutations that disturb normal development of the mammalian integument. The juvenile alopecia (jal), wooly (wly), frizzy-like (frzl), retarded hair growth (rhg), follicular dystrophy (fold), and wellhaarig (we), mutations affect hair morphology, development and maintenance;and may, in addition, disrupt skin-barrier function. The molecular assignment and functional analysis of the various processes impacted by these genes may lead to rational therapies (e.g. for alopecia or ichthyosis) and/or methods for regulating the function of the skin.