CHARACTERIZATION OF ZYGOTE ARREST ONE (ZAR1) IN NONHUMAN PRIMATES

非人类灵长类动物受精卵逮捕一 (ZAR1) 的特征

• 批准号: 8173204
• 负责人: Xuemei Wu
• 金额: $ 4.76万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8173204
• 关键词: Cells; Computer Retrieval of Information on Scientific Projects Database; Data; Development; Embryo; Embryonic Development; Female; Fertilization; Funding; Future; Genes; Genome; Goals; Grant; In Vitro; Infertility; Injection of therapeutic agent; Institution; Knockout Mice; Life; Macaca; Macaca mulatta; Messenger RNA; Microscopy; Monkeys; Mus; Oocytes; Orthologous Gene; Ovulation; Phenotype; Pre-implantation Embryo Development; Primates; RNA Interference; Research; Research Personnel; Resources; Role; Source; Staging; Time; Translational Research; United States National Institutes of Health; Woman; blastocyst; folliculogenesis; nonhuman primate; zygote

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. Zygote Arrest One (ZAR1) is a key oocyte factor required for early embryogenesis in mice. Zar1 null female mice are infertile due to a developmental arrest at the zygote stage despite fairly normal folliculogenesis and ovulation. Little is known about the mechanism underlying ZAR1's functions as well as the roles of ZAR1 in species other than mice. We identified a ZAR1 ortholog in rhesus monkeys. Similar to the mouse Zar1 gene, monkey ZAR1 is preferentially expressed in the oocyte and early preimplantation embryos. I hypothesize that ZAR1 is required for complete fertilization and the embryonic genome activation in both mice and rhesus macaques. Applying in vitro mRNA injection and RNAi in the oocyte/zygote from both species, I propose to: (1) rescue the developmental arrest phenotype in periovulatory oocytes and zygotes derived from Zar1 null mice. The goal of the aim is to determine the critical timing when ZAR1 is required, and to observe the progress of each developmental stage and dynamic translocalization of ZAR1 during the oocyte-to-embryo transition by time-lapse live cell microscopy; and (2), deplete macaque ZAR1 in fully-grown and mature oocytes to demonstrate the role of ZAR1 in preimplantation embryo development. The goal of the aim is to elucidate whether ZAR1 is functionally conserved in primates. Data obtained from this project will allow us to apply for R01 funds for future in-depth mechanistic studies on ZAR1 and translational research in oocyte quality assessment and infertility therapies in women.

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。 合子停滞一（ZAR1）是小鼠早期胚胎发生所需的关键卵母细胞因子。 ZAR1无效的雌性小鼠由于卵泡发生相当正常和排卵而在合子阶段的发育停滞，因此是不育的。 关于ZAR1功能以及ZAR1在小鼠以外的物种中的作用以及ZAR1的作用知之甚少。 我们在恒河猴中确定了ZAR1直系同源物。 与小鼠ZAR1基因相似，猴子Zar1优先表达在卵母细胞和早期植入前胚胎中。我假设在小鼠和恒河猕猴中完全受精和胚胎基因组激活是必需的。在这两种物种的卵母细胞/合子中施用体外mRNA注射和RNAi，我建议：（1）营救源自ZAR1 NULL小鼠的卵巢卵母细胞中的发育停滞表型和Zygotes。 目的的目的是确定需要ZAR1时的临界时机，并观察Zar1在卵母细胞到embryo在转变过程中通过延时活细胞显微镜的进展； （2），在完全生长和成熟的卵母细胞中耗尽猕猴的Zar1，以证明ZAR1在植入前胚胎发育中的作用。 目的的目的是阐明Zar1是否在灵长类动物中功能保守。 从该项目获得的数据将使我们能够申请R01资金，以对妇女的卵母细胞质量评估和不孕治疗的ZAR1和转化研究进行深入的内科机理研究。