Deficiency in the multicopy Sycp3-like X-linked genes Slx and Slxl1 causes major defects in spermatid differentiation.
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.
Cocquet
Julie
J
Division of Stem Cell Biology and Developmental Genetics, Medical Research Council National Institute for Medical Research, London, UK. jcocque@nimr.mrc.ac.uk
Ellis
Peter J I
PJ
Yamauchi
Yasuhiro
Y
Riel
Jonathan M
JM
Karacs
Thomas P S
TP
Rattigan
Aine
A
Ojarikre
Obah A
OA
Affara
Nabeel A
NA
Ward
Monika A
MA
Burgoyne
Paul S
PS
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
D009687:Nuclear Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C085792:Slx protein, mouse