IDENTIFICATION/CHARACTERIZATION OF POTENTIAL NOVEL MATERNAL-EFFECT GENE PRODUCTS

潜在新型母体效应基因产品的鉴定/表征

• 批准号: 7958441
• 负责人: Xuemei Wu
• 金额: $ 6.04万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-04 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7958441
• 关键词: Cells; Computer Retrieval of Information on Scientific Projects Database; Data; Domestic Animals; Embryonic Development; Experimental Designs; Factor Analysis; Family; Family member; Funding; Generations; Genes; Grant; Human; In Vitro; Institution; Knockout Mice; Leucine-Rich Repeat; Link; Macaca; Macaca mulatta; Mammals; Mediating; Monkeys; Mus; Mutation; Oocytes; Oogenesis; Play; Primates; Proteins; RNA Interference; Research; Research Personnel; Resources; Rodent; Role; Source; Staging; United States National Institutes of Health; blastocyst; in vivo; marenostrin; mouse model; nonhuman primate; novel; protein protein interaction; reproductive; yeast two hybrid system

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. We have identified a group of six NLRP (NLR family, pyrin domain containing) genes that are specifically expressed in the oocyte and early preimplantation embryos in rhesus macaques. Mouse NLRP5 has been demonstrated to be essential for embryogenesis beyond the 2-cell stage, and human NLRP7 was identified as the first maternal effect gene as the mutations of which have been linked to various forms of reproductive wastage. However, functions of other NLRP family members are not known. Our preliminary data in nonhuman primates, along with recent findings in rodents and domestic animals, suggest that these oocyte-specific NLRP genes play important roles during oogenesis and early embryo development in mammals. The purpose of this project is to reveal the functions of selected oocyte-specific NLRPs in mice and rhesus macaques. The specific aims are to: (1) characterize in vivo functions of mouse NLRP4A and 9B using knockout mouse models; (2) demonstrate the in vitro postovulatory roles of selected NLRP genes (mouse Nlrp4a, 5 and 9b; macaque NLRP4, 5 and 9) in mouse and macaque oocytes; (3) identify and analyze factors that interact with selected NLRP proteins in mouse and macaque oocytes. NLRP proteins contain a pyrin domain (PYD), a NACHT, and a leucine rich repeat (LRR) domain; both the PYD and LRR mediate protein-protein interactions. Experimental designs include generation and analysis of gene knockout mouse models, RNA interference (RNAi) in mouse and monkey oocytes, and application of yeast two-hybrid system in the mouse and macaque oocyte.

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代表。列出的机构是 对于中心，这不一定是调查员的机构。 我们已经确定了一组六个NLRP（NLR家族，含有吡啶结构域的）基因，该基因在恒河猕猴中特异性表达和早期植入前胚胎。 已证明小鼠NLRP5对于超出2细胞阶段的胚胎发生至关重要，并且人NLRP7被鉴定为第一个母体效应基因，因为其突变与各种形式的生殖废物有关。 但是，其他NLRP家族成员的功能尚不清楚。 我们在非人类灵长类动物中的初步数据，以及啮齿动物和家畜的最新发现，表明这些卵母细胞特异性的NLRP基因在卵子发生过程中起着重要作用，并且在哺乳动物的早期胚胎发育中起着重要作用。 该项目的目的是揭示小鼠和恒河猕猴中选定的卵母细胞特异性NLRP的功能。 具体目的是：（1）使用基因敲除鼠标模型来表征鼠标NLRP4A和9B的体内功能； （2）在小鼠和猕猴卵母细胞中演示了选定的NLRP基因（小鼠NLRP4A，5和9B；猕猴NLRP4、5和9）的体外卵巢后作用； （3）识别和分析与小鼠和猕猴卵母细胞中选定的NLRP蛋白相互作用的因子。 NLRP蛋白包含一个吡啶结构域（PYD），NACHT和一个富含亮氨酸的重复（LRR）结构域； PYD和LRR都介导蛋白质 - 蛋白质相互作用。 实验设计包括对基因敲除小鼠模型的产生和分析，小鼠和猴子卵母细胞中的RNA干扰（RNAi）以及在小鼠和猕猴卵母细胞中的酵母两杂化系统的应用。