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: 7348946
• 负责人: Xuemei Wu
• 金额: $ 7.68万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7348946
• 关键词: CHARACTERIZATION; ZYGOTE; ARREST; ZAR1; NONHUMAN

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. ZAR1 is a newly identified oocyte-expressed protein conserved during evolution. Female mice lacking ZAR1 are infertile due to a block of embryogenesis at the zygote stage. Thus, ZAR1 belongs to a small group of maternal-effect proteins that are required for the oocyte-to-embryo transition in mice. In humans, however, ZAR1 mRNA is detectable in both the ovary and the testis. To elucidate functions of ZAR1 in human fertility, we chose nonhuman primates as our mammalian system due to their close resemblance to humans in development. The aim of this project is to demonstrate potential functions of ZAR1 during early embryogenesis and identify key molecules that function at the oocyte-to-embryo transition in monkeys. We have discovered a monkey cDNA that is highly homologous to mouse and human ZAR1 gene, and determined the expression pattern of monkey ZAR1 mRNA. The specific aims are as follows: (1) to characterize ZAR1 protein expression in monkeys. Specific antibodies that recognize a highly conserved region of ZAR1 protein will be generated and used to determine ZAR1 expression in monkeys and humans; (2) to demonstrate potential functions of ZAR1 during early embryo development in monkeys. In vitro RNAi and transgenic techniques will be employed in monkey oocytes and early embryos; (3) to identify key molecules that function at the oocyte-to-embryo transition in nonhuman primates. We will perform microarray analysis to identify differentially expressed molecules in ZAR1 knockdown embryos. The study described here is among the first attempts to illustrate molecular mechanisms that regulate preimplantation embryogenesis in nonhuman primates.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中得到体现。列出的机构是中心的机构，不一定是研究者的机构。 ZAR1 是一种新发现的卵母细胞表达蛋白，在进化过程中保守。缺乏 ZAR1 的雌性小鼠由于受精卵阶段的胚胎发生受阻而无法生育。因此，ZAR1 属于小鼠卵母细胞向胚胎转变所需的一小群母体效应蛋白。然而，在人类中，ZAR1 mRNA 在卵巢和睾丸中均可检测到。为了阐明 ZAR1 在人类生育能力中的功能，我们选择非人类灵长类动物作为我们的哺乳动物系统，因为它们在发育过程中与人类非常相似。该项目的目的是证明 ZAR1 在早期胚胎发生过程中的潜在功能，并鉴定在猴子卵母细胞到胚胎转变过程中发挥作用的关键分子。我们发现了与小鼠和人ZAR1基因高度同源的猴cDNA，并确定了猴ZAR1 mRNA的表达模式。具体目的如下：（1）表征猴子中ZAR1蛋白的表达。将生成识别 ZAR1 蛋白高度保守区域的特异性抗体，并用于确定猴子和人类中 ZAR1 的表达； (2)证明ZAR1在猴子早期胚胎发育过程中的潜在功能。体外RNAi和转基因技术将应用于猴卵母细胞和早期胚胎； (3) 鉴定在非人灵长类动物卵母细胞到胚胎转变过程中发挥作用的关键分子。我们将进行微阵列分析来识别 ZAR1 敲低胚胎中的差异表达分子。这里描述的研究是阐明调节非人类灵长类动物植入前胚胎发生的分子机制的首次尝试之一。