Positional cloning of mutations that disrupt hair development in mice.

描述（由申请人提供）：哺乳动物外皮提供了一个特别有价值的系统，用于发育的遗传分析。影响毛发和皮肤形成或维持的突变很容易通过简单的视觉筛选检测到，并且这些变体通常显示出良好的生存能力。此外，毛被的后期发育（主要是在分娩后）及其在身体外部的位置允许容易获得发育中的突变体和野生型组织。虽然我们相信皮肤和毛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，只有对每种突变性状进行分子遗传分配，才能对改变的过程进行调查。因此，为了推进这类研究，我们建议（通过定位克隆方法）鉴定在一组隐性突变中被破坏的基因，这些突变导致小鼠的毛发和皮肤发育缺陷，包括：幼年型脱发（jal）、多毛（wly）、卷曲样（frzl）、毛发生长迟缓（rhg）、毛囊营养不良（fold）和wellhaarig（we）。这些研究还承诺通过为本科生和硕士生提供各种定义的项目来加强CCSU的研究活动，这些项目专注于分子分配和进一步表征这组知之甚少的遗传变异。 公共卫生相关性：这些调查有望加强中央康涅狄格州立大学的研究活动，同时推进干扰哺乳动物外皮正常发育的几种突变的分子特征。青少年脱发（jal）、羊毛状（wly）、卷曲样（frzl）、毛发生长迟缓（rhg）、毛囊营养不良（fold）和wellhaarig（we）突变影响毛发形态、发育和维持;此外，还可能破坏皮肤屏障功能。受这些基因影响的各种过程的分子分配和功能分析可能导致合理的治疗（例如脱发或鱼鳞病）和/或调节皮肤功能的方法。

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.