Investigation of the requirement for VRK1 in mammalian germ cell development

Vaccinia related kinase 1 (VRK1) is a highly conserved kinase that has been shown to be important for mitotic progression. VRK1 has also been implicated in germ cell development, but how it mediates mitotic or meiotic events during mammalian gametogenesis is not completely understood. Investigations conducted within this thesis utilized a Vrk1 gene trap mouse model to address the requirement for VRK1 in mammalian germ cell development. Similar to other models of VRK1 deficiency, mice homozygous for the Vrk1 gene trap insertion displayed fertility defects. The research presented here provides independent evidence that supports a role for VRK1 during the proliferation of male spermatogonia, as has been found by other groups. Moreover, this thesis presents findings that point to a function for VRK1 in coordinating proper chromosomal configurations during female meiosis. Thus, this work provides the first mammalian data indicative of a conserved role for VRK1 in female meiosis (published in Schober et al., 2011). Investigation of three previously determined phosphorylation targets of VRK1, p53 and histones H3 Ser10 and H2A Thr120, demonstrated that the activity of these substrates did not appear to be responsible for the observed fertility defects. Ultimately, this thesis has laid the groundwork for future exploration of the function of VRK1 during female mammalian meiosis.