Loss of TSLC1 causes male infertility due to a defect at the spermatid stage of spermatogenesis.
Tumor suppressor of lung cancer 1 (TSLC1), also known as SgIGSF, IGSF4, and SynCAM, is strongly expressed in spermatogenic cells undergoing the early and late phases of spermatogenesis (spermatogonia to zygotene spermatocytes and elongating spermatids to spermiation). Using embryonic stem cell technology to generate a null mutation of Tslc1 in mice, we found that Tslc1 null male mice were infertile. Tslc1 null adult testes showed that spermatogenesis had arrested at the spermatid stage, with degenerating and apoptotic spermatids sloughing off into the lumen. In adult mice, Tslc1 null round spermatids showed evidence of normal differentiation (an acrosomal cap and F-actin polarization indistinguishable from that of wild-type spermatids); however, the surviving spermatozoa were immature, malformed, found at very low levels in the epididymis, and rarely motile. Analysis of the first wave of spermatogenesis in Tslc1 null mice showed a delay in maturation by day 22 and degeneration of round spermatids by day 28. Expression profiling of the testes revealed that Tslc1 null mice showed increases in the expression levels of genes involved in apoptosis, adhesion, and the cytoskeleton. Taken together, these data show that Tslc1 is essential for normal spermatogenesis in mice.
van der Weyden
Louise
L
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom.
Arends
Mark J
MJ
Chausiaux
Oriane E
OE
Ellis
Peter J
PJ
Lange
Ulrike C
UC
Surani
M Azim
MA
Affara
Nabeel
N
Murakami
Yoshinori
Y
Adams
David J
DJ
Bradley
Allan
A
D000818:Animals; D017209:Apoptosis; D002448:Cell Adhesion / Q000235:genetics; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; D002454:Cell Differentiation; D003599:Cytoskeleton / Q000235:genetics; D004622:Embryo, Mammalian / Q000166:cytology; D004822:Epididymis / Q000737:chemistry / Q000166:cytology; D015870:Gene Expression; D007136:Immunoglobulins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D007248:Infertility, Male / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D013081:Sperm Motility / Q000235:genetics; D013087:Spermatids / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D013091:Spermatogenesis / Q000235:genetics*; D013094:Spermatozoa / Q000002:abnormalities* / Q000166:cytology / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism; D013737:Testis / Q000737:chemistry / Q000166:cytology; D025521:Tumor Suppressor Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D015854:Up-Regulation
C498598:Cadm1 protein, mouse; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D008565:Membrane Proteins; D025521:Tumor Suppressor Proteins