Establishing a Role for Kinesin-8 in Mammalian Germ Line Development

描述（由申请人提供）：这个小型研究项目侧重于激酶8，Kif18A的作用，它在细胞分裂中具有重要功能，广泛表达，但在发育的生殖系中是唯一需要的。哺乳动物Kif18A突变导致生殖细胞耗竭并最终导致不育；然而，突变小鼠的不育不是完全穿透的，而是取决于菌株背景。因此，在Kif18A消融的情况下，有遗传因素可以改善不孕症。Kif18a在种系发育中的独特作用直到最近才被揭示出来，并且Kif18a在种系中的功能机制尚未确定。这个小型研究项目的总体目标是提供建立Kif18A在生殖系发育中的作用机制所需的基本生物学数据，并创建一个遗传数据集，用于发现调节Kif18A依赖性生殖细胞耗竭的分子途径。这些数据将为一个更大的研究项目奠定基础，该项目关注的是哺乳动物生殖系生殖细胞分裂的专业化，在这个项目中，基因组完整性的维持是配子体发生和生育的重要组成部分。

DESCRIPTION (provided by applicant): This small research project focuses on the role of kinesin 8, Kif18A, which has an essential function in cell division and is broadly expressed, yet is uniquely required in the developing germ line. Mutations in mammalian Kif18A lead to germ cell depletion and ultimately infertility; however, infertility in mutant mice is not fully penetrat and is dependent on strain background. Therefore, there are genetic factors that ameliorate infertility in the context of Kif18A ablation. The unique role of Kif18a in germ line development has only recently been revealed and a mechanism for Kif18a function in the germ line has not been established. The overall goal of this small research project is to provide the basic biological data required to establish the mechanism by which Kif18A functions in germ line development and to create a genetic dataset for the discovery of the molecular pathways that modulate Kif18A dependent germ cell depletion. These data will contribute to the foundation of a larger research program focused on the specialization of germ cell division in the mammalian germ line, where maintenance of genome integrity is integral to gametogenesis and, critically, fertility.