Deficiency in the multicopy Sycp3-like X-linked genes Slx and Slxl1 causes major defects in spermatid differentiation.
Deficiency in the multicopy Sycp3-like X-linked genes Slx and Slxl1 causes major defects in spermatid differentiation.
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DOI：
10.1091/mbc.e10-07-0601
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发表时间：
2010-10-15
影响因子：
3.3
通讯作者：
Burgoyne PS
中科院分区：
文献类型：
--
作者：
Cocquet J;Ellis PJ;Yamauchi Y;Riel JM;Karacs TP;Rattigan A;Ojarikre OA;Affara NA;Ward MA;Burgoyne PS
Slx和Slxl1是存在于小鼠X染色体多个拷贝中的基因。使用转基因递送的小干扰rna破坏其功能，我们发现Slx和Slxl1对正常精子分化和男性生育能力很重要。人类和小鼠的性染色体富含圆形精子在减数分裂后向精子分化所需的多拷贝基因。Sly基因存在于小鼠Y染色体上的多个拷贝中，并编码一种蛋白质，这种蛋白质是减数分裂后性染色体表达的表观遗传调控所必需的。X染色体携带两个与Sly相关的多拷贝基因：Slx和Slxl1。在这里，我们研究了Slx/Slxl1的作用，使用转基因递送的小干扰rna来破坏它们的功能。我们发现Slx和Slxl1对正常精子分化和男性生育能力很重要。Slx/Slxl1缺乏导致精细胞伸长和精子释放延迟。高比例的延迟精子通过细胞凋亡被消除，导致精子数量减少。剩余的精子是异常的，运动能力和受精能力受损。微阵列分析显示，Slx/Slxl1缺陷影响精子细胞质中发生的代谢过程，但不会导致性染色体表达的全局扰动；这与Sly缺乏导致X和Y染色体基因上调的效果相反。这种差异可能是由于SLX/SLXL1存在于细胞质中，而SLY存在于精子的细胞核和细胞质中。
Slx and Slxl1 are genes present in multiple copies on the mouse X chromosome. Using transgenically-delivered small interfering RNAs to disrupt their function, we show that Slx and Slxl1 are important for normal sperm differentiation and male fertility. The human and mouse sex chromosomes are enriched in multicopy genes required for postmeiotic differentiation of round spermatids into sperm. The gene Sly is present in multiple copies on the mouse Y chromosome and encodes a protein that is required for the epigenetic regulation of postmeiotic sex chromosome expression. The X chromosome carries two multicopy genes related to Sly: Slx and Slxl1. Here we investigate the role of Slx/Slxl1 using transgenically-delivered small interfering RNAs to disrupt their function. We show that Slx and Slxl1 are important for normal sperm differentiation and male fertility. Slx/Slxl1 deficiency leads to delay in spermatid elongation and sperm release. A high proportion of delayed spermatids are eliminated via apoptosis, with a consequent reduced sperm count. The remaining spermatozoa are abnormal with impaired motility and fertilizing abilities. Microarray analyses reveal that Slx/Slxl1 deficiency affects the metabolic processes occurring in the spermatid cytoplasm but does not lead to a global perturbation of sex chromosome expression; this is in contrast with the effect of Sly deficiency which leads to an up-regulation of X and Y chromosome genes. This difference may be due to the fact that SLX/SLXL1 are cytoplasmic while SLY is found in the nucleus and cytoplasm of spermatids.