title: ALKBH4 depletion in mice leads to spermatogenic defects.
abstract: ALKBH4, an AlkB homologue in the 2-oxoglutarate and Fe2+ dependent hydroxylase family, has previously been shown to regulate the level of monomethylated lysine-84 in actin and thereby indirectly influences the ability of non-muscular myosin II to bind actin filaments. ALKBH4 modulates fundamental processes including cytokinesis and cell motility, and its depletion is lethal during early preimplantation embryo stage. The aim of this study was to investigate the effect of ALKBH4 deficiency in a physiological context, using inducible Alkbh4 knockout mice. Here, we report that ALKBH4 is essential for the development of spermatocytes during the prophase of meiosis, and that ALKBH4 depletion leads to insufficient establishment of the synaptonemal complex. We also show that ALKBH4 is localized in nucleolar structures of Sertoli cells, spermatogonia and primary spermatocytes.
authors.affiliation: Institute of Medical Microbiology, Oslo University Hospital, Rikshospitalet, University of Oslo, Oslo, Norway.
authors.forename: Anja
authors.initials: A
authors.lastname: Nilsen
authors.affiliation: Institute of Medical Microbiology, Oslo University Hospital, Rikshospitalet, University of Oslo, Oslo, Norway.
authors.forename: Markus
authors.initials: M
authors.lastname: Fusser
authors.affiliation: Section for Reproductive Medicine, Department of Gynecology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: Gareth
authors.initials: G
authors.lastname: Greggains
authors.affiliation: Section for Reproductive Medicine, Department of Gynecology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: Peter
authors.initials: P
authors.lastname: Fedorcsak
authors.affiliation: Institute of Medical Microbiology, Oslo University Hospital, Rikshospitalet, University of Oslo, Oslo, Norway; Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors.forename: Arne
authors.initials: A
authors.lastname: Klungland
mesh_terms: D000071501:AlkB Homolog 4, Lysine Demethylase; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D049308:Dioxygenases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D055786:Gene Knockout Techniques; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011418:Prophase / Q000235:genetics; D012708:Sertoli Cells / Q000378:metabolism; D013091:Spermatogenesis / Q000235:genetics*; D013737:Testis / Q000166:cytology
chemical_list: D049308:Dioxygenases; C585273:ALKBH4 protein, mouse; D000071501:AlkB Homolog 4, Lysine Demethylase