title: Mice deficient in the serine/threonine protein kinase VRK1 are infertile due to a progressive loss of spermatogonia.
abstract: The VRK1 protein kinase has been implicated as a pro-proliferative 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 (approximately 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.
authors.affiliation: Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Wiebe
authors.forename: R Jeremy
authors.initials: RJ
authors.lastname: Nichols
authors.forename: Tyler P
authors.initials: TP
authors.lastname: Molitor
authors.forename: Jill K
authors.initials: JK
authors.lastname: Lindgren
authors.forename: Paula
authors.initials: P
authors.lastname: Traktman
mesh_terms: D000483:Alleles; D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism; D049109:Cell Proliferation; D005260:Female; D007247:Infertility, Female / Q000378:metabolism; D007248:Infertility, Male / Q000378:metabolism*; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D008297:Male; D008540:Meiosis; D051379:Mice; D008810:Mice, Inbred C57BL; D008938:Mitosis; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012708:Sertoli Cells / Q000378:metabolism*; D013093:Spermatogonia / Q000378:metabolism*
chemical_list: D034961:Antigens, Nuclear; D051741:Kruppel-Like Transcription Factors; D018809:Proliferating Cell Nuclear Antigen; D000075722:Promyelocytic Leukemia Zinc Finger Protein; C513267:Zbtb16 protein, mouse; D017346:Protein Serine-Threonine Kinases; C484518:Vrk1 protein, mouse
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