Role of Tudor Domain Protein 1 in Mouse Germ Cells

描述(申请人提供)：卵母细胞的产生是一个复杂的过程，从早期胚胎发育开始，最终在成年后受精并随后发育出新的有机体。卵母细胞的发育程序要求它不仅表达自身发育所需的基因，而且在合子基因组激活之前表达早期胚胎的基因。后一过程需要储存母体RNA。最近，一个新的未知功能的生殖细胞特异性基因被克隆出来，称为Tudor结构域包含1(TDRD1)。含有Tudor结构域的蛋白质参与了RNA储存和代谢的调节，同样，TDRD1可能参与了卵母细胞mRNAs的调节。这项提议的长期目标是确定这种生殖细胞特异性基因的特征。本研究的具体目的是：1)充分鉴定和表征Tdrd1在卵子发生的早期胚胎、胎儿和成体阶段的表达；2)通过鉴定与其相互作用的蛋白来分析TDRD1在卵子发生中的功能；以及3)建立TDRD1的小鼠敲除模型，以测试TDRD1在体内对男性和女性生育的作用。这些研究可能有助于理解TDRD1在生殖细胞发育中的作用，进而了解卵子发生的过程。随着我们试图开发更成功的治疗人类不孕不育的方法，对卵子发生有更好的理解是必要的。

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.