title: AKAP9 is essential for spermatogenesis and sertoli cell maturation in mice.
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 p27(Kip1). 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.
authors.affiliation: Department of Biology, Middlebury College, Middlebury, VT 05753, USA.
authors.forename: Kerry J
authors.initials: KJ
authors.lastname: Schimenti
authors.forename: Sky K
authors.initials: SK
authors.lastname: Feuer
authors.forename: Laurie B
authors.initials: LB
authors.lastname: Griffin
authors.forename: Nancy R
authors.initials: NR
authors.lastname: Graham
authors.forename: Claire A
authors.initials: CA
authors.lastname: Bovet
authors.forename: Suzanne
authors.initials: S
authors.lastname: Hartford
authors.forename: Janice
authors.initials: J
authors.lastname: Pendola
authors.forename: Carl
authors.initials: C
authors.lastname: Lessard
authors.forename: John C
authors.initials: JC
authors.lastname: Schimenti
authors.forename: Jeremy O
authors.initials: JO
authors.lastname: Ward
mesh_terms: D054758:A Kinase Anchor Proteins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D054304:Anti-Mullerian Hormone / Q000235:genetics / Q000378:metabolism; D018031:Connexin 43 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism; D017629:Gap Junctions / Q000648:ultrastructure; D008297:Male; D008540:Meiosis / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D009928:Organ Specificity; D021381:Protein Transport; D012708:Sertoli Cells / Q000166:cytology* / Q000378:metabolism; D013091:Spermatogenesis / Q000235:genetics*; D013094:Spermatozoa / Q000166:cytology / Q000378:metabolism; D008941:Spindle Apparatus / Q000378:metabolism; D037021:Thyroid Hormone Receptors alpha / Q000235:genetics / Q000378:metabolism; D019108:Tight Junctions / Q000648:ultrastructure; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
chemical_list: D054758:A Kinase Anchor Proteins; C464931:Akap9 protein, mouse; D018031:Connexin 43; D008869:Microtubule-Associated Proteins; D037021:Thyroid Hormone Receptors alpha; D062826:Zonula Occludens-1 Protein; D050760:Cyclin-Dependent Kinase Inhibitor p27; D054304:Anti-Mullerian Hormone
keywords: Sertoli cells; infertility; mouse; protein kinase A; spermatogenesis