Disruption of spermatogenic cell adhesion and male infertility in mice lacking TSLC1/IGSF4, an immunoglobulin superfamily cell adhesion molecule.
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.
Yamada
Daisuke
D
Tumor Suppression and Functional Genomics Project, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
Yoshida
Midori
M
Williams
Yuko N
YN
Fukami
Takeshi
T
Kikuchi
Shinji
S
Masuda
Mari
M
Maruyama
Tomoko
T
Ohta
Tsutomu
T
Nakae
Dai
D
Maekawa
Akihiko
A
Kitamura
Tadaichi
T
Murakami
Yoshinori
Y
D000818:Animals; D017209:Apoptosis; D002448:Cell Adhesion / Q000235:genetics; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics; D005091:Exons / Q000235:genetics; D015870:Gene Expression; D020869:Gene Expression Profiling; D007136:Immunoglobulins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D007248:Infertility, Male / Q000235:genetics*; D007985:Leydig Cells / Q000166:cytology; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D012661:Semen / Q000166:cytology; D017384:Sequence Deletion; D012708:Sertoli Cells / Q000648:ultrastructure; D013091:Spermatogenesis / Q000235:genetics*; D013094:Spermatozoa / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; 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