The significance of ODF1 for male germ cell differentiation and motility by generation and analysis of ODF1 deficient mice

近年来，精子尾部细胞骨架在男性不育诊断中越来越受到关注，因为精子尾部相关缺陷可能导致精子运动能力下降，最终导致不育。不幸的是，精子尾部的形态缺陷主要没有追溯到它们的分子原因，这主要是因为构建精子尾部细胞骨架的蛋白质成分的分析受到它们的不溶解性的阻碍。在脊椎动物精子尾部中发现的细胞骨架结构是外致密纤维（odf），其主要成分为ODF1和ODF2。由于其α-晶体蛋白结构域，ODF1被鉴定为小热休克蛋白，因此被重新命名为HSPB10，推测其具有伴侣蛋白的功能。为了分析ODF1在精子尾部细胞骨架形成中的作用及其对稳定性和运动性的影响，我们已经开始敲除ODF1。本研究的目的是建立杂合型和纯合型ODF1缺陷小鼠及其表型分析。此外，我们将探讨ODF1的异位表达是否会影响培养细胞中ODF2纤维、初级纤毛或中心体周期的形成。

The sperm tail cytoskeleton has got increasing attention in male infertility diagnostics over the years as sperm tail associated defects may impair sperm motility eventually resulting in infertility. Unfortunately, morphological defects of the sperm tail mainly have not been traced back to their molecular cause largely because analysis of the protein components that build up the sperm tail cytoskeleton was hampered by their insolubility. Cytoskeletal structures exclusively found in the sperm tails of vertebrates are the outer dense fibers (ODFs) whose main components have been identified as ODF1 and ODF2. Due to its α-crystallin domain ODF1 was identified as a small heat shock protein and thus renamed into HSPB10 suggesting a putative chaperone function. To analyse ODF1 function in formation of the sperm tail cytoskeleton and its impact for stability and motility we have started to knock out ODF1. Objective of the proposal is the generation of heterozygous and homozygous ODF1 deficient mice and their phenotypic analyses. Additionally, we will ask whether ectopic expression of ODF1 might affect the formation of ODF2 fibers, the primary cilium, or the centrosome cycle in cultured cells.