Disruption of spermatogenic cell adhesion and male infertility in mice lacking TSLC1/IGSF4, an immunoglobulin superfamily cell adhesion molecule
Disruption of spermatogenic cell adhesion and male infertility in mice lacking TSLC1/IGSF4, an immunoglobulin superfamily cell adhesion molecule
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DOI：
10.1128/mcb.26.9.3610-3624.2006
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发表时间：
2006-05-01
影响因子：
5.3
通讯作者：
Murakami, Y
中科院分区：
文献类型：
--
作者：
Yamada, D;Yoshida, M;Murakami, Y
TSLC1/IGSF4是一种免疫球蛋白超家族分子，主要在脑、肺和睾丸中表达，在上皮细胞黏附、肿瘤侵袭和突触形成中发挥重要作用。我们通过破坏Tslc1/Igsf4基因的外显子1产生了Tslc1/Igsf4缺陷小鼠，发现Tslc1(-/-)小鼠出生时具有预期的孟德尔比例，但Tslc1(-/-)雄性小鼠不育。11周龄成年Tslc1(-/-)小鼠的睾丸重量是Tslc1(+/+)小鼠的88%，精液中精子数约为Tslc1(+/+)小鼠的0.01%。组织学分析显示，Tslc1(-/-)小鼠生精管内圆形精细胞和粗线型精母细胞未能附着于支持细胞，脱落到管腔内，细胞发生凋亡。另一方面，精原细胞和间质细胞，包括间质细胞，基本上没有受到影响。在Tslc1(+/+)小鼠中，TSLc1/IGSF4在中间精原细胞到粗线期早期精母细胞的生精细胞以及在第7步或以后的精子细胞中均有表达。这些结果表明，TSLC1/IGSF4的表达对于精母细胞和精子细胞与Sertoli细胞的黏附和向成熟精子的正常分化是必不可少的。
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.