ALKBH4 depletion in mice leads to spermatogenic defects

Anja Nilsen; Markus Fusser; Gareth Greggains; Peter Fedorcsak; Arne Klungland

doi:10.1371/journal.pone.0105113

ALKBH4 depletion in mice leads to spermatogenic defects

PLoS One. 2014 Aug 25;9(8):e105113. doi: 10.1371/journal.pone.0105113. eCollection 2014.

Authors

Anja Nilsen¹, Markus Fusser¹, Gareth Greggains², Peter Fedorcsak², Arne Klungland³

Affiliations

¹ Institute of Medical Microbiology, Oslo University Hospital, Rikshospitalet, University of Oslo, Oslo, Norway.
² Section for Reproductive Medicine, Department of Gynecology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
³ Institute of Medical Microbiology, Oslo University Hospital, Rikshospitalet, University of Oslo, Oslo, Norway; Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

AlkB Homolog 4, Lysine Demethylase
Animals
Apoptosis / genetics
Dioxygenases / genetics
Dioxygenases / metabolism
Dioxygenases / physiology*
Gene Knockout Techniques
Male
Mice
Mice, Knockout
Prophase / genetics
Sertoli Cells / metabolism
Spermatogenesis / genetics*
Testis / cytology

Substances

Dioxygenases
ALKBH4 protein, mouse
AlkB Homolog 4, Lysine Demethylase

Grants and funding

This work was supported by the Norwegian Research Council and the Norwegian Cancer Society. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.