The Multicopy Gene Sly Represses the Sex Chromosomes in the Male Mouse Germline after Meiosis

Studies of mice with Y chromosome long arm deficiencies suggest that the male-specific region (MSYq) encodes information required for sperm differentiation and postmeiotic sex chromatin repression (PSCR). Several genes have been identified on MSYq, but because they are present in more than 40 copies each, their functions cannot be investigated using traditional gene targeting. Here, we generate transgenic mice producing small interfering RNAs that specifically target the transcripts of the MSYq-encoded multicopy gene Sly (Sycp3-like Y-linked). Microarray analyses performed on these Sly-deficient males and on MSYq-deficient males show a remarkable up-regulation of sex chromosome genes in spermatids. Two sets of samples were examined: (1) Total RNA isolated from separated round spermatids of young adult males (8 weeks postpartum) with Yq deletions or shSLY targeted knockdown, compared to age- and strain-matched controls. (2) Total RNA isolated from whole testis of juvenile males (17 days post partum) with shSLY targeted knockdown, compared to age- and strain-matched controls.针对携带Y染色体长臂缺失的小鼠开展的研究显示，雄性特异性区域（MSYq）编码了精子分化与减数分裂后性染色质沉默（PSCR）所需的遗传信息。目前已在MSYq上鉴定出多个基因，但由于每个基因的拷贝数均超过40个，传统基因靶向技术无法对其功能开展研究。本研究构建了可特异性靶向MSYq编码的多拷贝基因Sly（Sycp3样Y连锁基因）转录本的小干扰RNA转基因小鼠。对该Sly缺陷雄性小鼠及MSYq缺陷雄性小鼠开展的微阵列分析显示，精子细胞内的性染色体基因出现显著上调。本次研究共检测两组样本：（1）从携带Yq缺失或shSLY介导敲低的年轻成年雄性（产后8周）的分离圆形精子细胞中提取的总RNA，以同年龄、同品系的野生型小鼠作为对照；（2）从接受shSLY介导敲低的幼年雄性（产后17天）的全睾丸组织中提取的总RNA，以同年龄、同品系的野生型小鼠作为对照。