title: The kinase VRK1 is required for normal meiotic progression in mammalian oogenesis.
abstract: The kinase VRK1 has been implicated in mitotic and meiotic progression in invertebrate species, but whether it mediates these events during mammalian gametogenesis is not completely understood. Previous work has demonstrated a role for mammalian VRK1 in proliferation of male spermatogonia, yet whether VRK1 plays a role in meiotic progression, as seen in Drosophila, has not been determined. Here, we have established a mouse strain bearing a gene trap insertion in the VRK1 locus that disrupts Vrk1 expression. In addition to the male proliferation defects, we find that reduction of VRK1 activity causes a delay in meiotic progression during oogenesis, results in the presence of lagging chromosomes during formation of the metaphase plate, and ultimately leads to the failure of oocytes to be fertilized. The activity of at least one phosphorylation substrate of VRK1, p53, is not required for these defects. These results are consistent with previously defined functions of VRK1 in meiotic progression in Drosophila oogenesis, and indicate a conserved role for VRK1 in coordinating proper chromosomal configuration in female meiosis.
authors.affiliation: Department of Genetics, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Carolyn S
authors.initials: CS
authors.lastname: Schober
authors.forename: Fulya
authors.initials: F
authors.lastname: Aydiner
authors.forename: Carmen J
authors.initials: CJ
authors.lastname: Booth
authors.forename: Emre
authors.initials: E
authors.lastname: Seli
authors.forename: Valerie
authors.initials: V
authors.lastname: Reinke
mesh_terms: D000818:Animals; D033481:Chromosomes, Mammalian / Q000502:physiology; D005260:Female; D006657:Histones / Q000378:metabolism; D007247:Infertility, Female / Q000235:genetics; D007248:Infertility, Male / Q000235:genetics; D008297:Male; D008540:Meiosis; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D016254:Mutagenesis, Insertional; D009865:Oocytes / Q000502:physiology; D009866:Oogenesis; D009929:Organ Size; D009928:Organ Specificity; D010053:Ovary / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012670:Seminiferous Epithelium / Q000002:abnormalities; D013091:Spermatogenesis; D013737:Testis / Q000378:metabolism / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D006657:Histones; D016159:Tumor Suppressor Protein p53; D017346:Protein Serine-Threonine Kinases; C484518:Vrk1 protein, mouse