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 通过分子克隆分离这些基因，并阐明 它们的突变导致雄性不育或精子的机制 功能障碍 由于没有关于它们基因的信息 产品，将使用以下两种克隆策略：（i） 随机分离17号染色体衍生的基因组克隆 或来自HpaII微小碎片（HTF）岛附近， 存在于与基因，和（ii）染色体的分离 17-编码的cDNA克隆，其在 正常和无菌的小鼠睾丸。 17号染色体衍生的基因组 将对从HTF岛屿附近分离的克隆进行筛选 睾丸转录本的存在，而克隆 随机隔离将被区域定位，以确定那些 在已知的雄性生殖细胞影响附近定位的克隆 的位点 将使用与这些基因座足够接近的克隆 构建“区域性”基因组文库， 筛查睾丸转录物的存在。 在我们 初步研究，使用第一个克隆策略， 导致了一种新的睾丸特异性基因的分离， 显然不符合任何已知的男性生殖细胞 影响位于17号染色体上的基因座。 这个基因，这个蛋白质 含有假定的“锌指”基序的产品也将 在本提案中详细说明。 很可能我们将分离和表征的小鼠基因 这里有他们的人类对应物。 一些人类男性 不孕症可以考虑。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相关性， 应该为我们提供基础知识， 男性不育症的诊断和治疗。

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.