Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan; Department of Experimental Genome Research, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.
Department of Experimental Genome Research, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.
J Reprod Immunol. 2024 Jun;163:104252. doi: 10.1016/j.jri.2024.104252. Epub 2024 Apr 29.
More than 1200 genes have been shown in the database to be expressed predominantly in the mouse testes. Advances in genome editing technologies such as the CRISPR/Cas9 system have made it possible to create genetically engineered mice more rapidly and efficiently than with conventional methods, which can be utilized to screen genes essential for male fertility by knocking out testis-enriched genes. Finding such genes related to male fertility would not only help us understand the etiology of human infertility but also lead to the development of male contraceptives. In this study, we generated knockout mice for 12 genes (Acrv1, Adgrf3, Atp8b5, Cfap90, Cfap276, Fbxw5, Gm17266, Lrrd1, Mroh7, Nemp1, Spata45, and Trim36) that are expressed predominantly in the testis and examined the appearance and histological morphology of testes, sperm motility, and male fertility. Mating tests revealed that none of these genes is essential for male fertility at least individually. Notably, knockout mice for Gm17266 showed smaller testis size than the wild-type but did not exhibit reduced male fertility. Since 12 genes were not individually essential for male fertilization, it is unlikely that these genes could be the cause of infertility or contraceptive targets. It is better to focus on other essential genes because complementary genes to these 12 genes may exist.
数据库中显示，超过 1200 个基因主要在小鼠睾丸中表达。基因组编辑技术的进步，如 CRISPR/Cas9 系统，使得比传统方法更快、更有效地创建基因工程小鼠成为可能，这可以用来通过敲除富含睾丸的基因来筛选对雄性生育力至关重要的基因。发现与雄性生育力相关的此类基因不仅有助于我们了解人类不育症的病因，还可能导致男性避孕药的开发。在这项研究中，我们生成了 12 个基因（Acrv1、Adgrf3、Atp8b5、Cfap90、Cfap276、Fbxw5、Gm17266、Lrrd1、Mroh7、Nemp1、Spata45 和 Trim36）的敲除小鼠，这些基因主要在睾丸中表达，并检查了睾丸的外观和组织形态、精子运动能力和雄性生育力。交配试验表明，这些基因中没有一个对雄性生育力是必不可少的，至少不是单独起作用的。值得注意的是，Gm17266 敲除小鼠的睾丸比野生型小，但雄性生育力并没有降低。由于这 12 个基因单独对雄性受精不是必需的，因此这些基因不太可能是不育症的原因或避孕靶点。最好将注意力集中在其他必需基因上，因为这些 12 个基因可能存在互补基因。
