WILD DERIVED GENETIC VARIATION

一系列远亲的老鼠物种已经被测试了它们的 能够与实验室菌株杂交， 可繁殖的杂种 其中，M.斯普雷图斯被证明是 作为一种高度分化的亲本资源， 但在F1杂交组合中仍能存活。 在这些 杂交，女性是肥沃的，他们可以与任何回交 亲本基因型 相比之下，杂交雄性不育， 或者在减数分裂中期I之后没有精子发生的证据。 初步工作表明，X-Y染色体配对失败是一种遗传学上的遗传学异常。 这些杂种的减数分裂前期的突出特征，它可能 导致不育表型。 总体而言，最初的工作 表明，正常的X-Y配对是一个基本的必要条件， 减数分裂中期Ⅰ以后进程与小鼠属的分歧 可能在X-Y配对区缺乏足够的序列同源性， 这种互动发生。 因此，不育的杂种雄性可以提供 关于减数分裂和精子发生调节的重要信息。 从进化的角度来看，X-Y配对区域的分歧可能 是物种形成过程中的一个重要特征 这项建议 概述了解决雄性不育遗传基础的具体目标， 小鼠物种杂交，包括X-Y染色体配对在这一过程中的作用， 表型和配对失败的分子基础的分析。 该计划还保留了强大的研究资源， 使用广泛的小鼠样本的特定研究问题集 基因库作为特殊的研究资源。 支持的研究资源 这项赠款包括1）一套多样化的野生衍生，实验室 保持远交种小鼠，2）一系列同源株携带 各种不同基因的野生衍生等位基因，3）罕见的近交系 对更广泛的研究至关重要的菌株和突变株 我们部门的几个调查人员的利益和4）一个小系列 从我们项目中进行的ENU诱变研究中回收的突变体。 因此，建议的一个中心主题是继续使用这一资源 以及一个大纲计划，以提高其对我们和更广泛的社区的价值 老鼠遗传学和医学研究的成果

A series of distantly related Mus species have been tested for their ability to interbreed with laboratory strains and to produce viable, fertile hybrids. Among these species, M. spretus has proved to be extremely valuable as a parental resource stock that is highly diverged from laboratory mice but still viable in F1 hybrid combinations. In these hybrids, the females are fertile and they can be backcrossed with either parental genotype. By contrast, the hybrid males are sterile with little or no evidence of spermatogenesis beyond metaphase I of meiosis. Preliminary work indicates that a failure of X-Y chromosome pairing is a prominent feature of the meiotic prophase of these hybrids and that it may be causal of the sterile phenotype. Taken together, the initial work indicates that normal X-Y pairing is an essential requisite for the progression of meiosis beyond metaphase I and that divergent Mus species may lack sufficient sequence homology in the X-Y pairing region to allow this interaction to occur. Thus, the sterile hybrid males may provide important information about the regulation of meiosis and spermatogenesis. From an evolutionary perspective, the divergence of X-Y pairing regions may be an important feature in the process of speciation. This proposal outlines specific aims to address the genetic basis of male sterility in mouse species hybrids including the role of X-Y chromosome pairing in this phenotype and an analysis of the molecular basis for the pairing failure. The program also retains a strong research resource combined with a specific set of research questions that use a broad sampling of the mouse gene pool as special research resources. The research resources supported by this grant include 1) a diverse set of wild-derived, laboratory maintained outbred Mus species, 2) a series of congenic strains carrying wild-derived alleles for a variety of different genes, 3) rare inbred strains and mutant stocks that are critical to the broader research interests of several investigators in our department and 4) a small series of mutants recovered from ENU mutagenesis studies conducted in our program. Thus a central theme of the proposal is the continuation of this resource and an outline program to improve its value to us and the broader community of mouse genetics and medical research.