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，从早期胚胎发生开始，到成年受精和随后的新生物发育达到高潮。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。后一个过程需要母体rna的储存。最近，一种功能未知的生殖细胞特异性基因——tudor domain containing 1 （TDRD1）被克隆出来。都铎结构域蛋白参与RNA储存和代谢的调控，同样，TDRD1可能参与卵母细胞mrna的调控。这项建议的长期目标是表征这种生殖细胞特异性基因。该提案的具体目标是：1)充分识别和表征Tdrd1在早期胚胎、胎儿和卵发生的成年阶段的表达；2)通过鉴定与TDRD1相互作用的蛋白，分析TDRD1在卵子发生中的功能；3)建立小鼠TDRD1基因敲除模型，以检验TDRD1在体内对雌雄生殖能力的作用。这些研究将有可能导致了解TDRD1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多成功的治疗人类不孕症的方法。

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.