Mice deficient in the serine/threonine protein kinase VRK1 are infertile due to a progressive loss of spermatogonia

Matthew S. Wiebe, R. Jeremy Nichols, Tyler P. Molitor, Jill K. Lindgren, Paula Traktman

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

The VRK1 protein kinase has been implicated as a proproliferative factor. Genetic analyses of mutant alleles of the Drosophila and Caenorhabditis elegans VRK1 homologs have revealed phenotypes ranging from embryonic lethality to mitotic and meiotic defects with resultant sterility. Herein, we describe the first genetic analysis of murine VRK1. Two lines of mice containing distinct gene-trap integrations into the Vrk1 locus were established. Insertion into intron 12 (GT12) spared VRK1 function, enabling the examination of VRK1 expression in situ. Insertion into intron 3 (GT3) disrupted VRK1 function, but incomplete splicing to the gene trap rendered this allele hypomorphic (∼15% of wild-type levels of VRK1 remain). GT3/GT3 mice are viable, but both males and females are infertile. In testes, VRK1 is expressed in Sertoli cells and spermatogonia. The infertility of GT3/GT3 male mice results from a progressive defect in spermatogonial proliferation or differentiation, culminating in the absence of mitotic and meiotic cells in adult testis. These data demonstrate an important role for VRK1 in cell proliferation and confirm that the need for VRK1 during gametogenesis is evolutionarily conserved.

Original languageEnglish (US)
Pages (from-to)182-193
Number of pages12
JournalBiology of reproduction
Volume82
Issue number1
DOIs
StatePublished - 2010

Keywords

  • Gametogenesis
  • Infertility
  • Kinases
  • Proliferation
  • Protein kinase
  • Signal transduction
  • Spermatogenesis
  • Spermatogonia
  • Testis
  • VRK1

ASJC Scopus subject areas

  • Reproductive Medicine
  • Cell Biology

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