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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此，可以在其他清晰的条目中表示。列出的机构是 对于中心，这不一定是调查员的机构。 男性因素不育是全世界的一个重大关注点。大多数男性不育 病例是特发性的。在雄性中，原始生殖细胞（PGC）迁移，增殖和定居 生殖脊最终形成睾丸绳，在那里与Sertoli细胞建立接触。钥匙 调节原始生殖细胞迁移和增殖的因素尚不完全了解。这 该项目的长期目标是描述生殖细胞与Sertoli细胞中的机理 睾丸。对生殖细胞如何发展和功能的机械理解与临床有关 雄性不育症的疾病表现为仅塞尔托利细胞综合征，目前没有 治疗。开始探索男性生殖细胞的发育生物学，并了解 人类仅细胞综合征的病理生物学，我们已经表征了荒谬，自然 发生纯合隐性小鼠突变体。术的突变睾丸组织学非常相似 仅Sertoli细胞综合征患者的病例，并展示了仅衬有Sertoli细胞和 没有生殖细胞。我们将测试中心假设，即细胞自主缺陷导致 术中术中完全不存在生殖细胞。这些研究将确定基因 负责术中缺乏生殖细胞，并为 进一步的功能丧失和功能获得的遗传方法，以了解生殖细胞迁移和 功能。最后，这项工作将建立萎缩突变体作为一种遗传跟踪的新鼠标模型 人类男性不育症条件与仅Sertoli细胞仅细胞小管和生殖细胞性相关，因此 影响男性生育恢复的临床方案。