KANSAS U COBRE: GERM CELL DEVELOPMENT IN THE ATRICHOSIS MUTANT MOUSE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 男性因素不育症是全世界普遍关注的问题。大多数男性不育 这些病例是特发性的。在雄性中，原始生殖细胞(PGC)迁移、增殖并在 生殖器脊最终形成睾丸索，在那里它们与支持细胞建立联系。钥匙 调节原始生殖细胞迁移和增殖的因素尚不完全清楚。这个 该项目的长期目标是阐明生殖细胞与支持细胞相互作用的机制。 睾丸。对生殖细胞如何发育和功能的机械性理解与临床相关 表现为仅支持细胞综合征的男性不育状况，目前尚无 治疗。开始探索男性生殖细胞的发育生物学，并了解 人类仅支持细胞综合征的病理生物学，我们已经表征了闭锁，自然 发生纯合子隐性小鼠突变。睾丸发育不全突变型组织学与 显示仅有支持细胞综合征患者的肾小管内仅有支持细胞和 不含生殖细胞。我们将检验一个中心假设，即细胞自主缺陷导致 发育不全突变的睾丸中完全没有生殖细胞。这些研究将确定该基因(S) 负责在闭锁突变小鼠中缺乏生殖细胞，并为 进一步的功能丧失和功能获得的遗传学方法来理解生殖细胞迁移和 功能。最后，这项工作将建立闭锁突变作为一种可遗传追踪的新小鼠模型 人类男性不育症与仅有支持细胞的小管和生殖细胞再生障碍有关，因此 影响男性生育能力恢复的临床方案。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Male factor infertility is a significant concern throughout the world. The majority of the male infertility cases are idiopathic. In the male, primordial germ cells (PGCs) migrate, proliferate, and colonize the genital ridges to ultimately form testicular cords, where they establish contacts with the Sertoli cells. Key factors that regulate primordial germ cell migration and proliferation are not completely understood. The long-term goal of this project is to delineate the mechanisms of germ cell interactions with Sertoli cells in the testis. A mechanistic understanding of how germ cells develop and function is relevant to clinical conditions of male infertility that manifest as Sertoli cell-only syndrome for which there is currently no treatment. To begin to explore the developmental biology of the male germ cells and to understand the pathobiology of the human Sertoli cell-only syndrome, we have characterized atrichosis, the naturally occurring homozygous recessive mouse mutant. The atrichosis mutant testis histology closely resembles that of Sertoli cell-only syndrome patients and demonstrates tubules lined with only Sertoli cells and contains no germ cells. We will test the central hypothesis that a cell autonomous defect leads to complete absence of germ cells in the atrichosis mutant testis. These studies will identify the gene(s) responsible for the absence of germ cells in the atrichosis mutant mouse and provide a starting point for further loss-of-function and gain-of-function genetic approaches to understand germ cell migration and function. Finally, this work will establish atrichosis mutant as a genetically trackable new mouse model for human male infertility conditions associated with Sertoli cell-only tubules and germ cell aplasia, thus impacting clinical protocols of male fertility restoration.