Quill Timothy A, Wang Dan, Garbers David L
Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Mol Cell Endocrinol. 2006 May 16;250(1-2):84-92. doi: 10.1016/j.mce.2005.12.031. Epub 2006 Jan 18.
Successful natural reproduction normally requires vigorously motile spermatozoa. Using a signal peptide trapping strategy, we identified two new genes, a putative sperm Na+/H+ exchanger (sNHE) and the putative cation channel CatSper2, with unique and essential roles in sperm motility. Disruption of the sNHE or CatSper2 genes in mice caused male infertility due to immotile spermatozoa or failed motility hyperactivation, respectively, without other apparent abnormalities. The immotility phenotype of the sNHE null spermatozoa appears to result from an intimate association of sNHE and the atypical adenylyl cyclase (sAC), while a failure of calcium entry requiring an apparent CatSper1 and -2 heteromeric ion channel correlates with a hyperactivation defect in these null animals. The specific expression of sNHE and the CatSpers in spermatozoa and their required function in cell motility make them excellent potential targets for the development of novel male contraceptives.
成功的自然繁殖通常需要活力旺盛的精子。我们采用信号肽捕获策略，鉴定出两个新基因，一个推测的精子钠氢交换体（sNHE）和推测的阳离子通道CatSper2，它们在精子活力中具有独特且至关重要的作用。破坏小鼠体内的sNHE或CatSper2基因分别导致雄性不育，原因是精子不动或活力超激活失败，且无其他明显异常。sNHE基因敲除精子的不动表型似乎是由于sNHE与非典型腺苷酸环化酶（sAC）密切相关，而钙内流失败（需要明显的CatSper1和-2异源离子通道）与这些基因敲除动物的超激活缺陷相关。sNHE和CatSpers在精子中的特异性表达及其在细胞活力中的必需功能，使其成为开发新型男性避孕药的极佳潜在靶点。
