IDENTIFICATION/CHARACTERIZATION OF NOVEL MATERNAL-EFFECT GENE PRODUCTS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 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，这些蛋白质是将自己的命运指引到可受精的卵子并产生健康胚胎所必需的。我们鉴定了一组在猕猴卵母细胞中特异表达的六个NLRP(NLR家族，PYRIN结构域)基因；在植入前胚胎发生过程中，这些NLRP仅来自母体(母亲)基因组，并随着胚胎基因组的激活而迅速衰退。除了小鼠NLRP5是超过2-细胞期的胚胎发育所必需的，其他NLRP家族成员的功能尚不清楚。我们对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的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。本项目的目的是揭示选定的卵母细胞特异性NLRPs在小鼠和恒河猴中的功能。其具体目的是：(1)利用基因敲除小鼠模型研究小鼠NLRP4A、4F和14的体内功能；(2)展示选定的NLRP基因(小鼠Nlrp4a、4f和14；猕猴NLRP4、5和14)在体外对小鼠和猕猴卵母细胞的促排卵作用；(3)鉴定和分析与猕猴中选定的NLRP蛋白相互作用的卵巢因子。由于猕猴与人类在生殖生理和遗传学上非常相似，本项目得出的结果将很容易推断到人类的生殖，并为未来的翻译研究提供基础。

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.