Loss of TSLC1 Causes Male Infertility Due to a Defect at the Spermatid Stage of Spermatogenesis
- 1 May 2006
- journal article
- Published by Taylor & Francis in Molecular and Cellular Biology
- Vol. 26 (9) , 3595-609
- https://doi.org/10.1128/mcb.26.9.3595-3609.2006
Abstract
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.Keywords
This publication has 52 references indexed in Scilit:
- The tumor suppressor TSLC1/NECL-2 triggers NK-cell and CD8+ T-cell responses through the cell-surface receptor CRTAMBlood, 2005
- Spermatid differentiation requires the assembly of a cell polarity complex downstream of junctional adhesion molecule-CNature, 2004
- Targeted Inactivation of Testicular Nuclear Orphan Receptor 4 Delays and Disrupts Late Meiotic Prophase and Subsequent Meiotic Divisions of SpermatogenesisMolecular and Cellular Biology, 2004
- Association of a lung tumor suppressor TSLC1 with MPP3, a human homologue of Drosophila tumor suppressor DlgOncogene, 2003
- Loss of Nectin-2 at Sertoli-Spermatid Junctions Leads to Male Infertility and Correlates with Severe Spermatozoan Head and Midpiece Malformation, Impaired Binding to the Zona Pellucida, and Oocyte PenetrationBiology of Reproduction, 2003
- Expression and Functional Characterization of the Adhesion Molecule Spermatogenic Immunoglobulin Superfamily in the Mouse Testis1Biology of Reproduction, 2003
- FLIP is expressed in mouse testis and protects germ cells from apoptosisCell Death & Differentiation, 2003
- Microarray data normalization and transformationNature Genetics, 2002
- A 2-Mb Sequence-Ready Contig Map and a Novel Immunoglobulin Superfamily Gene IGSF4 in the LOH Region of Chromosome 11q23.2Genomics, 1999
- Cell Adhesion: The Molecular Basis of Tissue Architecture and MorphogenesisPublished by Elsevier ,1996