项目名称: 睾丸特异表达激酶TSSK4调节雄性小鼠生殖的机制研究
项目编号: No.31301202
项目类型: 青年科学基金项目
立项/批准年度: 2014
项目学科: 生物科学
项目作者: 韦有衡
作者单位: 复旦大学
项目金额: 20万元
中文摘要: 我们在前面的研究工作中已经阐明TSSK4 是睾丸特异表达的丝/苏氨酸激酶,它特异的表达在变形及成熟的精子细胞中,在体内外TSSK4具有磷酸化和自身磷酸化活性,其自身磷酸化位点是第197位的苏氨酸(wei,2013)。在本研究中我们已经成功的制备了TSSK4基因缺失小鼠模型,发现该基因缺失后雄性小鼠的生殖能力显著下降,其原因是精子尾巴结构异常以及由此导致的具有运动能力的精子数显著下降。但TSSK4是如何通过调节精子尾巴结构和运动从而调节雄性小鼠生殖能力的分子机制仍然不清楚,本项目拟对这一部分内容展开研究。我们首先拟采用多种实验手段寻找可能被 TSSK4调控的分子靶标,探寻该(些)靶分子与精子尾巴结构和运动的关系,进而研究TSSK4和该(些)目标分子的调控关系从而阐释TSSK4调控雄性小鼠生殖能力的分子机制,为后续临床上研究男性不育症的遗传因素提供一定的理论基础。
中文关键词: 雄性生殖;磷酸化;TSSK4;;
英文摘要: In our previous work, we have elucidated that TSSK4 is a testes specific Serine/Threonine protein kinase. It is exclussively expressed in elongating and mature sperms. Both in vitro and in vivo, TSSK4 has phosphorylation and autophosphorylation activity.In vitro, it can phosphorylate itself on Thr-197 (Wei, 2013). In our present work, we have successfully generated TSSK4 deletion mice model. With the deletion of TSSK4, male mice show sub-fertility phenotypes according to abnormal sperm flagella structures as well as much less sperms with normal motile activity, but the molecular mechanism on TSSK4 regulating male fertility is remained to be elucidated. In this applying project, we will put all our efforts on elucidating this molecular mechanism. Firstly, we will find out the down-stream target molecular(s) that is (are) modified or regulated by TSSK4 using a variety of experimental procedures. Consecutive research work will be conducted to elucidate the relationships between TSSK4 and the candidated targeting molecules. With the completion of this project, mechanism on TSSK4 regulating male reproduction will be elucidated which will provide some theoretical basis for further clinical genetic research work concerning male sterility.
英文关键词: male reproduction;phosphorylation;TSSK4;;