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

KANSAS U COBRE：无生长突变小鼠生殖细胞的发育

• 批准号: 8167984
• 负责人: T. RAJENDRA KUMAR
• 金额: $ 22万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8167984
• 关键词: Cell Communication; Cells; Clinical; Clinical Protocols; Computer Retrieval of Information on Scientific Projects Database; Defect; Development; Developmental Biology; Fertility; Funding; Genes; Genetic; Genital system; Germ Cells; Goals; Grant; Histology; Human; Infertility; Institution; Kansas; Male Infertility; Mutant Strains Mice; Patients; Proliferating; Research; Research Personnel; Resources; Sertoli cell only syndrome; Source; Structure of primordial sex cell; Testing; Testis; United States National Institutes of Health; Work; cell motility; gain of function; human male; loss of function; male; mouse model; mutant; restoration; sertoli cell

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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 男性因素不育是全世界关注的一个重大问题。大多数男性不育症 病例为特发性。在男性中，原始生殖细胞（PGCs）迁移，增殖，并定殖于 生殖嵴最终形成睾丸索，在那里它们与支持细胞建立联系。关键 调节原始生殖细胞迁移和增殖的因素尚未完全了解。的 本项目的长期目标是描述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理解与临床相关。 男性不育症表现为支持细胞综合征，目前还没有 治疗开始探索雄性生殖细胞的发育生物学，并了解 在人类支持细胞综合征的病理生物学中，我们已经描述了无毛症， 发生纯合隐性小鼠突变体。无毛突变型睾丸组织学与 只有支持细胞综合征患者，并显示肾小管内衬只有支持细胞， 不含生殖细胞。我们将测试中心假设，即细胞自主缺陷导致 在无毛突变的睾丸中完全没有生殖细胞。这些研究将确定基因（S） 负责缺乏生殖细胞的无毛突变小鼠，并提供一个起点， 进一步的功能丧失和功能获得遗传学方法来了解生殖细胞迁移， 功能最后，这项工作将建立一个遗传可追踪的新的小鼠模型， 与仅有支持细胞的小管和生殖细胞发育不全相关的人类男性不育病症，因此 影响男性生育力恢复的临床方案。