Role of Tudor Domain Protein 1 in Mouse Germ Cells

描述（由申请人提供）：卵母细胞的产生是一个复杂的过程，始于早期胚胎发生，在成年时达到高潮，受精并随后发育成新的生物体。卵母细胞的发育程序要求它不仅表达自身发育的基因，而且表达合子基因组激活前早期胚胎的基因。后一个过程需要储存母体RNA。最近，一个新的生殖细胞特异性基因被克隆出来，称为tudor domain containing 1（TDRD 1）。含有Tudor结构域的蛋白质参与RNA储存和代谢的调节，类似地，TDRD 1可能参与卵母细胞mRNA的调节。该提案的长期目标是表征这种生殖细胞特异性基因。该提案的具体目的是：1）充分鉴定和表征TDRD 1在卵子发生的早期胚胎、胎儿和成体阶段的表达; 2）通过鉴定与TDRD 1相互作用的蛋白质来分析TDRD 1在卵子发生中的功能; 3）生成TDRD 1的小鼠敲除模型，以测试TDRD 1在雄性和雌性生育力中的体内作用。这些研究将可能导致了解TDRD 1在生殖细胞发育中的功能，进而了解卵子发生过程。更好地了解卵子发生是必要的，因为我们试图开发更成功的治疗人类不育症。

DESCRIPTION (provided by applicant): The generation of oocytes is a complex process that begins in early embryogenesis and which culminates in the adult with the fertilization and subsequent development of a new organism. The developmental program of the oocyte requires that it expresses genes not only for its own development, but also that of the early embryo prior to zygotic genome activation. The latter process requires the storage of maternal RNAs. Recently, a novel germ cell specific gene of unknown function, called tudor domain containing 1 (TDRD1), has been cloned. Tudor domain containing proteins have been implicated in the regulation of RNA storage and metabolism, and similarly, TDRD1 may be involved in the regulation of oocyte mRNAs. The long-term objective of this proposal is to characterize this germ cell specific gene. The specific aims of this proposal are to 1) fully identify and characterize the expression of Tdrd1 in early embryonic, fetal, and adult stages of oogenesis; 2) analyze the function of TDRD1 in oogenesis by identifying the proteins with which it interacts; and 3) generate a mouse knockout model of TDRD1 in order to test the in vivo role of TDRD1 in male and female fertility. These studies will potentially lead to an understanding TDRD1 function in germ cell development, and in turn, of the process of oogenesis. A better understanding of oogenesis is necessary as we try to develop more successful treatments for human infertility.