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Molecular and Cellular Biology, May 2006, p. 3610-3624, Vol. 26, No. 9
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.9.3610-3624.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Disruption of Spermatogenic Cell Adhesion and Male Infertility in Mice Lacking TSLC1/IGSF4, an Immunoglobulin Superfamily Cell Adhesion Molecule

Tumor Suppression and Functional Genomics Project,¹ Genetics Division, National Cancer Center Research Institute, Tokyo, Japan,³ Department of Pathology, Sasaki Institute, Sasaki Foundation, Tokyo, Japan,² Department of Urology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan⁴

Received 5 August 2005/ Returned for modification 1 October 2005/ Accepted 30 January 2006

TSLC1/IGSF4, an immunoglobulin superfamily molecule, is predominantly expressed in the brain, lungs, and testes and plays important roles in epithelial cell adhesion, cancer invasion, and synapse formation. We generated Tslc1/Igsf4-deficient mice by disrupting exon 1 of the gene and found that Tslc1^–/– mice were born with the expected Mendelian ratio but that Tslc1^–/– male mice were infertile. In 11-week-old adult Tslc1^–/– mice, the weight of a testis was 88% that in Tslc1^+/+ mice, and the number of sperm in the semen was approximately 0.01% that in Tslc1^+/+ mice. Histological analysis revealed that the round spermatids and the pachytene spermatocytes failed to attach to the Sertoli cells in the seminiferous tubules and sloughed off into the lumen with apoptosis in the Tslc1^–/– mice. On the other hand, the spermatogonia and the interstitial cells, including Leydig cells, were essentially unaffected. In the Tslc1^+/+ mice, TSLC1/IGSF4 expression was observed in the spermatogenic cells from the intermediate spermatogonia to the early pachytene spermatocytes and from spermatids at step 7 or later. These findings suggest that TSLC1/IGSF4 expression is indispensable for the adhesion of spermatocytes and spermatids to Sertoli cells and for their normal differentiation into mature spermatozoa.

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