Positional cloning of mutations that disrupt hair development in mice.

描述(申请人提供)：哺乳动物被片为发育的遗传分析提供了一个特别有价值的系统。通过简单的视觉屏幕可以很容易地检测到影响头发和皮肤形成或维护的突变，并且这些变体通常显示出良好的生存能力。此外，毛茸茸的皮毛发育较晚(主要是在分娩后)，其在身体外部的位置使其很容易获得发育中的突变和野生型组织。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基因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使对改变过程的研究继续进行。因此，为了推进这些研究，我们建议(通过位置克隆方法)在一组导致小鼠毛发和皮肤发育缺陷的隐性突变中识别被破坏的基因，这些突变包括：青少年脱发(JAL)、毛发(WLY)、卷毛样(FRZL)、毛发生长迟缓(RHG)、毛囊营养不良(Fold)和良好毛发(WE)。这些研究还承诺加强CCSU的研究活动，为本科生和硕士研究生提供各种明确的项目，重点是分子分配和对这组鲜为人知的遗传变异的进一步表征。 公共卫生相关性：这些研究承诺加强中康涅狄格州立大学的研究活动，同时推进几种扰乱哺乳动物体壁正常发育的突变的分子表征。青少年脱发(JAL)、毛发(Wly)、卷发样(FRZL)、毛发生长迟缓(RHG)、毛囊营养不良(Fold)和毛发健康(WE)，突变会影响毛发的形态、发育和维护；此外，还可能破坏皮肤屏障功能。对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.