Deficiency in the Multicopy Sycp3-Like X-Linked Genes Slx and Slxl1 Causes Major Defects in Spermatid Differentiation
| Autor: | Julie Cocquet, Nabeel A. Affara, Thomas P. S. Karacs, Obah A. Ojarikre, Áine Rattigan, Monika A. Ward, Jonathan M. Riel, Peter J.I. Ellis, Yasuhiro Yamauchi, Paul S. Burgoyne |
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| Rok vydání: | 2010 |
| Předmět: |
Male
endocrine system Gene Dosage Apoptosis Mice Transgenic Biology Y chromosome Mice 03 medical and health sciences 0302 clinical medicine Testis medicine Animals RNA Messenger RNA Small Interfering Spermatogenesis Molecular Biology reproductive and urinary physiology Sperm motility X chromosome 030304 developmental biology Regulation of gene expression 0303 health sciences Sex Chromosomes Sperm Count Spermatid urogenital system Gene Expression Profiling Nuclear Proteins Chromosome Spermatid differentiation Articles Cell Biology Spermatids Sperm Molecular biology Fertility medicine.anatomical_structure Gene Expression Regulation Cell Biology of Disease Gene Knockdown Techniques Sperm Motility 030217 neurology & neurosurgery |
| Zdroj: | Molecular Biology of the Cell |
| ISSN: | 1939-4586 1059-1524 |
| DOI: | 10.1091/mbc.e10-07-0601 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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