MOLECULAR CHARACTERIZATION OF THE MIS TYPE II RECEPTOR

MIS II 型受体的分子表征

• 批准号: 2196367
• 负责人: JOSE M. TEIXEIRA
• 金额: $ 2.37万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-08-22 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2196367
• 关键词: MOLECULAR; CHARACTERIZATION; MIS; TYPE; II

Mullerian inhibiting substance (MIS) is responsible for regression of Mullerian ducts during the course of male reproductive tract development and curiously, MIS is also expressed in both adult male testes and female ovaries, albeit at much lower levels. It is a TGF-beta family protein expressed in fetal Sertoli cells of the testis which transduces its signal into the cell via a heteromeric complex of type I and II receptors. The molecular mechanisms governing these processes are largely unknown as is the role played by MIS in the adult. Our primary goal is to identify and characterized the MIS receptor components in order to delineate the molecular details of MIS-mediated regression of Mullerian ducts and to determine the roles played by MIS in the adult. We have cloned putative MIS type I and type II receptors in the laboratory, R1 and pBS7, respectively, which are expressed in the appropriate tissues in a temporal manner. The type I receptor is being studied by others in the laboratory, whereas the molecular characterization of the MIS type II receptor (pBS7), is the focus of this proposal. We will confirm by qualitative and quantitative techniques that pBS7 is the MIS type II receptor. We will perform gene disruption in mice to determine the phenotype of type II receptor knockout. Finally, we will study the 5' flanking region of the type II receptor in order to better understand the molecular mechanism underlying its transcriptional regulation. The results of these efforts will allow us to understand the roles played by MIS in fetal development and in the adult.

苗勒管抑制物质（MIS）是负责退化的， 男性生殖道发育过程中的苗勒管 而且奇怪的是，MIS也在成年男性睾丸和女性睾丸中表达， 卵巢，尽管水平要低得多。 它是一种TGF-β家族蛋白 在睾丸的胎儿支持细胞中表达， 通过I型和II型的异聚体复合物向细胞中传递信号 受体。 控制这些过程的分子机制是 很大程度上未知的是MIS在成人中所起的作用。 我们的首要 目的是识别和表征MIS受体成分， 为了描述MIS介导的退行性变的分子细节， 苗勒管，并确定MIS在成人中发挥的作用。 我们已经克隆了假定的MIS I型和II型受体， 实验室，R1和pBS 7，分别表达在 适当的组织在时间的方式。 I型受体被 其他人在实验室里研究，而分子 MIS II型受体（pBS 7）的表征是本发明的焦点。 提议 我们将通过定性和定量技术确认 pBS 7是MIS II型受体。 我们将进行基因破坏 以确定II型受体敲除的表型。 最后，我们将研究II型受体的5'侧翼区， 为了更好地了解其分子机制， 转录调控 这些努力的结果将使我们 了解MIS在胎儿发育中的作用， 成年人了