Expression of the v-Mos oncogene in male meiotic germ cells of transgenic mice results in metaphase arrest.
To explore the role of pp39mos in male germ cell meiosis, we have constructed transgenic mice carrying either the c-Mos or v-Mos genes linked to the human male germ cell-specific phosphoglycerate kinase-2 promoter. All male transgenic mice bearing the v-Mos but not the c-Mos construct were sterile due to arrest of germ cells at metaphase I. Immunocytochemistry performed on sections from control and c-Mos transgenic testes with eight different monoclonal and polyclonal antisera against either alpha-, beta- or gamma-tubulins demonstrated that all could recognize MI spermatocyte spindles from control and c-Mos transgenics, but only one monoclonal anti-microtubule sera decorated the spindles of v-Mos-arrested meiotic figures. Western blot analyses with this one serum revealed a change in proteins in the v-Mos samples. Immunocytochemistry with the MPM-2 monoclonal antibody, which is specific for epitopes phosphorylated during mitosis, demonstrated an increase in cytoplasmic and spindle-associated phosphoproteins in arrested v-Mos spermatocytes. Western analysis with MPM-2 showed an increase in a M(r) 50,000-55,000 and a M(r) 25,000-29,000 protein in Mos transgenic testes when compared to controls. An anti-MAP kinase antibody demonstrated an increase in all four MAP kinases in testes of transgenic mice. Thus, overexpression of pp39v-mos during male germ cell meiosis resulted in an alteration of various cell cycle related kinases and cytostatic factor-like arrest at MI.
Rosenberg
M P
MP
Glaxo Research Institute, Department of Pharmacology, Research Triangle Park, North Carolina 27709, USA.
Aversa
C R
CR
Wallace
R
R
Propst
F
F
D000818:Animals; D001483:Base Sequence; D006801:Humans; D007248:Infertility, Male / Q000209:etiology; D008297:Male; D008540:Meiosis; D008677:Metaphase; D051379:Mice; D008822:Mice, Transgenic; D008870:Microtubules / Q000378:metabolism; D008969:Molecular Sequence Data; D017232:Oncogene Proteins v-mos / Q000096:biosynthesis* / Q000235:genetics / Q000633:toxicity; D010735:Phosphoglycerate Kinase / Q000096:biosynthesis / Q000235:genetics; D010750:Phosphoproteins / Q000096:biosynthesis; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis; D017231:Proto-Oncogene Proteins c-mos / Q000096:biosynthesis* / Q000235:genetics; D013094:Spermatozoa / Q000166:cytology / Q000502:physiology*; D013737:Testis / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure
D017232:Oncogene Proteins v-mos; D010750:Phosphoproteins; D017346:Protein Serine-Threonine Kinases; D017231:Proto-Oncogene Proteins c-mos; D010735:Phosphoglycerate Kinase