title: Deficiency in the multicopy Sycp3-like X-linked genes Slx and Slxl1 causes major defects in spermatid differentiation.
abstract: 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.
authors.affiliation: Division of Stem Cell Biology and Developmental Genetics, Medical Research Council National Institute for Medical Research, London, UK. jcocque@nimr.mrc.ac.uk
authors.forename: Julie
authors.initials: J
authors.lastname: Cocquet
authors.forename: Peter J I
authors.initials: PJ
authors.lastname: Ellis
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yamauchi
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Riel
authors.forename: Thomas P S
authors.initials: TP
authors.lastname: Karacs
authors.forename: Aine
authors.initials: A
authors.lastname: Rattigan
authors.forename: Obah A
authors.initials: OA
authors.lastname: Ojarikre
authors.forename: Nabeel A
authors.initials: NA
authors.lastname: Affara
authors.forename: Monika A
authors.initials: MA
authors.lastname: Ward
authors.forename: Paul S
authors.initials: PS
authors.lastname: Burgoyne
mesh_terms: D000818:Animals; D017209:Apoptosis; D005298:Fertility / Q000235:genetics; D018628:Gene Dosage / Q000235:genetics*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D012730:Sex Chromosomes / Q000235:genetics; D013076:Sperm Count; D013081:Sperm Motility; D013087:Spermatids / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D013091:Spermatogenesis / Q000235:genetics*; D013737:Testis / Q000378:metabolism / Q000473:pathology
chemical_list: D009687:Nuclear Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C085792:Slx protein, mouse