AKAP9 Is Essential for Spermatogenesis and Sertoli Cell Maturation in Mice |
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Authors: | Kerry J Schimenti Sky K Feuer Laurie B Griffin Nancy R Graham Claire A Bovet Suzanne Hartford Janice Pendola Carl Lessard John C Schimenti Jeremy O Ward |
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Institution: | §Department of Biology, Middlebury College, Middlebury, Vermont 05753;*Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853;†Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853;‡The Jackson Laboratory, Bar Harbor, Maine 04609 |
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Abstract: | Mammalian male fertility relies on complex inter- and intracellular signaling during spermatogenesis. Here we describe three alleles of the widely expressed A-kinase anchoring protein 9 (Akap9) gene, all of which cause gametogenic failure and infertility in the absence of marked somatic phenotypes. Akap9 disruption does not affect spindle nucleation or progression of prophase I of meiosis but does inhibit maturation of Sertoli cells, which continue to express the immaturity markers anti-Mullerian hormone and thyroid hormone receptor alpha in adults and fail to express the maturation marker p27Kip1. Furthermore, gap and tight junctions essential for blood–testis barrier (BTB) organization are disrupted. Connexin43 (Cx43) and zona occludens-1 are improperly localized in Akap9 mutant testes, and Cx43 fails to compartmentalize germ cells near the BTB. These results identify and support a novel reproductive tissue-specific role for Akap9 in the coordinated regulation of Sertoli cells in the testis. |
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Keywords: | spermatogenesis Sertoli cells mouse protein kinase A infertility |
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