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。 哺乳动物卵母细胞是一种高度分化的细胞，其中包含一套独特的蛋白质，将自己的命运引导到可肥料的鸡蛋并产生健康的胚胎。 我们确定了一组六个NLRP（NLR家族，含有吡啶结构域的）基因，这些基因在恒河猕猴中特异性表达。在植入前的胚胎发生过程中，这些NLRP仅源自母体（母亲）基因组，并在胚胎基因组激活后迅速衰减。 除了在2细胞阶段以外的胚胎发生所需的小鼠NLRP5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基因在卵子发生和早期胚胎发育期间在多个阶段起着重要作用。 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，4F和14的体内功能； （2）在小鼠和猕猴的卵母细胞中演示了选定的NLRP基因（小鼠NLRP4A，4F和14;猕猴NLRP4、5和14）的体外分散后作用； （3）识别和分析与猕猴中选定的NLRP蛋白相互作用的卵巢因子。 由于猕猴与人之间的生殖生理和遗传学非常相似，因此从该项目中得出的发现很容易被推断为人类的生殖，并为将来的翻译研究提供了基础。