Positional cloning of mutations that disrupt hair development in mice.

描述（由申请人提供）：哺乳动物的被皮为发育的遗传分析提供了一个特别有价值的系统。影响头发和皮肤形成或维持的突变很容易通过简单的视觉屏幕检测到，这些变异通常表现出良好的生存能力。此外，毛发的后期发育（主要是在分娩后）及其在身体外部的位置使发育突变型和野生型组织变得容易。虽然我们相信皮肤和头发的变异可以通过这些方式，为哺乳动物发育的遗传控制提供独特的见解，但很明显，只有每个突变特征的分子遗传分配才能允许对改变过程的调查继续进行。因此，为了推进这类研究，我们建议（通过位置克隆方法）识别在一组隐性突变中被破坏的基因，这些突变导致小鼠毛发和皮肤发育缺陷，包括：幼年脱发（jal）、毛茸茸（wly）、卷曲样（frzl）、毛发生长迟缓（rhg）、毛囊营养不良（fold）和脱发（we）。这些研究还承诺通过为本科生和硕士水平的学生提供各种明确的项目来加强CCSU的研究活动，这些项目侧重于分子分配和进一步表征这组知之甚少的遗传变异。

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.