MALE GERM CELL-AFFECTING GENES ON MOUSE CHROMOSOME 17

许多影响精子发生的基因已经被定位到 小鼠17号染色体。拟议项目的总体目标是 用分子克隆的方法分离这些基因，并阐明它们之间的关系 它们的突变导致男性不育或精子的机制 功能障碍。因为没有关于他们基因的信息 产品，将使用以下两种克隆策略：(I) 随机分离17号染色体来源的基因组克隆 或来自HpaII微小碎片(HTF)岛附近 与基因相关的存在，以及(Ii)染色体的分离 差异表达的17个编码的cDNA克隆 正常和无菌的小鼠睾丸。17号染色体衍生的基因组 从HTF岛附近分离出来的克隆将被筛选 对于睾丸转录的存在，而克隆 随机隔离的将按地区本地化，以识别 在已知雄性生殖细胞附近映射的克隆-影响 精神错乱。将使用与这些基因座映射足够近的克隆 构建“地区性”基因组文库，然后 检查是否有睾丸转录记录。在我们的 初步研究表明，使用第一克隆策略已经 导致了一种新的睾丸特异基因的分离 显然不符合任何已知的男性生殖细胞- 位于17号染色体上的影响基因。这个基因，蛋白质 其产品含有推定的“锌指”图案，也将 在这项提案中有详细的描述。 很可能我们将分离和鉴定的小鼠基因 这里有他们的人类同行。某些形式的人类男性 不孕不育也可以算在内。因为它们的突变。在这 从某种意义上说，拟议的项目具有直接的临床意义和 应该为我们提供基本知识，这些知识应该会导致更好的 人类男性不育的诊断和治疗。

Numerous genes that affect spermatogenesis have been mapped to mouse chromosome 17. The overall goal of the proposed project is to isolate these genes by molecular cloning and to elucidate the mechanisms by which their mutations cause male sterility or sperm dysfunction. Since no information is available on their gene products, the following two cloning strategies will be used: (i) isolation of chromosome 17-derived genomic clones either at random or from the vicinity of HpaII tiny fragment (HTF) islands that exist in association with genes, and (ii) isolation of chromosome 17-encoded cDNA clones that are differentially expressed between normal and sterile mouse testes. The chromosome 17-derived genomic clones isolated from the vicinity of HTF islands will be screened for the presence of testicular transcripts, whereas the clones isolated at random will be regionally localized to identify those clones that map in the vicinity of known male germ cell-affecting loci. The clones that map close enough to such loci will be used to construct "regional" genomic libraries, which will then be screened for the presence of testicular transcripts. In our preliminary studies, the use of the first cloning strategy has resulted in the isolation of a novel testis-specific gene that apparently does not correspond to any of the known male germ cell- affecting loci located on chromosome 17. This gene, the protein products of which contain putative "zinc finger" motifs, will also be characterized in detail in this proposal. It is likely that the mouse genes we will isolate and characterize here have their human counterparts. Some forms of human male infertility may be accounted. for by their mutations. In this sense, the proposed project has direct clinical relevance and should provide us with basic knowledge that should lead to better diagnosis and treatment of human male infertility.