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The cell adhesion molecule BT-IgSF is essential for a functional blood-testis barrier and male fertility in mice

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Item Type:Article
Title:The cell adhesion molecule BT-IgSF is essential for a functional blood-testis barrier and male fertility in mice
Creators Name:Pelz, L. and Purfürst, B. and Rathjen, F.G.
Abstract:The Ig-like cell adhesion molecule (IgCAM) brain- and testis-specific immunoglobulin superfamily (BT-IgSF) protein plays a major role in male fertility in mice. However, the molecular mechanism by which BT-IgSF supports fertility is unclear. Here, we found that it is localized in Sertoli cells at the blood-testis barrier (BTB) and at the apical ectoplasmic specialization. Absence of BT-IgSF in Sertoli cells in both global and conditional mouse mutants (i.e. AMHCre and Rosa26CreERT2 lines) resulted in male infertility, atrophic testes with vacuolation, azoospermia, and spermatogenesis arrest. Although transcripts of junctional proteins such as connexin43, ZO-1, occludin, and claudin11 were upregulated in the absence of BT-IgSF, the functional integrity of the BTB was impaired, as revealed by injection of a BTB-impermeable component into the testes under in vivo conditions. Disruption of the BTB coincided with mislocalization of connexin43, which was present throughout the seminiferous epithelium and not restricted to the BTB as in wildtype tissues, suggesting impaired cell-cell communication in the BT-IgSF-KO mice. Since EM images revealed a normal BTB structure between Sertoli cells in the BT-IgSF-KO mice, we conclude that infertility in these mice is most likely caused by a functionally impaired BTB. In summary, our results indicate that BT-IgSF is expressed at the BTB and is required for male fertility by supporting the functional integrity of the BTB.
Keywords:Blood-Testis Barrier, BT-IgSF (IgSF11), Connexin43, IgCAM, Male Fertility, Cell Adhesion, Testis, Spermatogenesis, IgCAM BT-IgSF (IgSF11), Animals, Mice
Source:Journal of Biological Chemistry
ISSN:0021-9258
Publisher:American Society for Biochemistry and Molecular Biology (U.S.A.)
Volume:292
Number:52
Page Range:21490-21503
Date:29 December 2017
Additional Information:Copyright © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.
Official Publication:https://doi.org/10.1074/jbc.RA117.000113
PubMed:View item in PubMed

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