IDENTIFICATION/CHARACTERIZATION OF NOVEL MATERNAL-EFFECT GENE PRODUCTS

新型母体效应基因产品的鉴定/表征

• 批准号: 7715919
• 负责人: Xuemei Wu
• 金额: $ 1.11万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7715919
• 关键词: Cells; Computer Retrieval of Information on Scientific Projects Database; Data; Domestic Animals; Embryo; Embryonic Development; Family; Family member; Funding; Future; Genes; Genetic; Genome; Grant; Human; In Vitro; Institution; Knock-out; Macaca; Macaca mulatta; Mothers; Mus; Oocytes; Oogenesis; Ovarian; Play; Proteins; Purpose; Reproduction; Reproductive Physiology; Research; Research Personnel; Resources; Rodent; Role; Set protein; Source; Staging; Translational Research; United States National Institutes of Health; base; egg; in vivo; marenostrin; mouse model; nonhuman primate; novel

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. The mammalian oocyte is a highly differentiated cell and contains a unique set of proteins necessary for directing its own fate to a fertilizable egg and producing a healthy embryo. We identified a group of six NLRP (NLR family, pyrin domain containing) genes that are specifically expressed in the oocyte in rhesus macaques; during preimplantation embryogenesis, these NLRPs are exclusively derived from the maternal (mother's) genome and decay rapidly upon embryo genome activation. Except for mouse NLRP5 that is required for embryogenesis beyond the 2-cell stage, functions of other NLRP family members are not known. Our preliminary data from nonhuman primates, along with recent findings in rodents and domestic animals, suggest that these oocyte-specific NLRP genes play important roles at multiple stages during oogenesis and early embryo development. 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, 4F and 14 using knockout mouse models; (2) demonstrate the in vitro postovulatory roles of selected NLRP genes (mouse Nlrp4a, 4f and 14; macaque NLRP4, 5 and 14) in mouse and macaque oocytes; (3) identify and analyze ovarian factors that interact with selected NLRP proteins in macaques. Due to the close resemblance in reproductive physiology and genetics between rhesus macaques and humans, the findings derived from this project will be easily extrapolated to human reproduction, and provide a basis for future translational research.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 哺乳动物卵母细胞是一种高度分化的细胞，含有一组独特的蛋白质，这些蛋白质是指导其自身命运形成受精卵并产生健康胚胎所必需的。 我们鉴定了一组 6 个 NLRP（NLR 家族，含有热蛋白结构域）基因，这些基因在恒河猴的卵母细胞中特异性表达；在植入前胚胎发生过程中，这些 NLRP 完全源自母体基因组，并在胚胎基因组激活后迅速衰减。 除了小鼠 NLRP5 是 2 细胞阶段以上胚胎发生所必需的之外，其他 NLRP 家族成员的功能尚不清楚。 我们来自非人类灵长类动物的初步数据，以及最近在啮齿动物和家畜中的发现表明，这些卵母细胞特异性 NLRP 基因在卵子发生和早期胚胎发育的多个阶段发挥着重要作用。 该项目的目的是揭示小鼠和恒河猴中选定的卵母细胞特异性 NLRP 的功能。 具体目标是：（1）利用敲除小鼠模型表征小鼠NLRP4A、4F和14的体内功能； (2) 证明选定的 NLRP 基因（小鼠 Nlrp4a、4f 和 14；猕猴 NLRP4、5 和 14）在小鼠和猕猴卵母细胞中的体外排卵后作用； (3) 鉴定并分析与猕猴中选定的 NLRP 蛋白相互作用的卵巢因子。 由于恒河猴与人类在生殖生理学和遗传学方面非常相似，该项目的研究结果将很容易外推到人类生殖，并为未来的转化研究提供基础。