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1 Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita 565-0871, Japan
2 Department of Molecular Biology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka 537-8511, Japan
3 KAN Research Institute Inc., 93 Chudoji-Awatamachi, Shimogyo-ku, Kyoto 600-8815, Japan
Seminiferous epithelia of the testes contain two types of intercellular junctions: SertoliSertoli junctions and Sertolispermatid junctions. The former junctions are equipped with tight and adherens junctions while the latter junctions are not. Ca2+-independent immunoglobulin-like cell-cell adhesion molecules, nectin-2 and nectin-3, asymmetrically localize at the Sertoli cell side and at the spermatid side of Sertolispermatid junctions, respectively. They heterophilically trans-interact to make contact between the two cells. Nectin-2/ mice have shown male-specific infertility, disrupted Sertolispermatid junctions and morphologically impaired spermatid development. Here we report testicular phenotypes of nectin-3/ mice exhibiting male-specific infertility. Nectin-3/ mice had defects in the later steps of sperm morphogenesis including distorted nuclei and abnormal distribution of mitochondria, as well as in localization of nectin-2 at the Sertolispermatid junctions. Transplantation of wild-type spermatogenic stem cells into the nectin-3/ testes partially rescued these defects in sperm morphogenesis. These results indicate that the heterophilic trans-interaction between nectin-2 and nectin-3 is essential for the formation and maintenance of Sertolispermatid junctions that plays a critical role in spermatid development.
* Correspondence: E-mail: ytakai{at}molbio.med.osaka-u.ac.jp
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