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.

[1]  K. Okazaki,et al.  Parthenogenetic activation of oocytes in c-mos-deficient mice , 1994, Nature.

[2]  M. Evans,et al.  Disruption of c-mos causes parthenogenetic development of unfertilized mouse eggs , 1994, Nature.

[3]  E. Nishida,et al.  Requirement for the MAP kinase kinase/MAP kinase cascade in Xenopus oocyte maturation. , 1994, The EMBO journal.

[4]  G. V. Vande Woude Embryology. On the loss of Mos. , 1994, Nature.

[5]  A. Lewellyn,et al.  Induction of metaphase arrest in cleaving Xenopus embryos by MAP kinase. , 1993, Science.

[6]  J. Ruderman,et al.  Mos induces the in vitro activation of mitogen-activated protein kinases in lysates of frog oocytes and mammalian somatic cells. , 1993, Molecular biology of the cell.

[7]  T. Hunt,et al.  The c‐mos proto‐oncogene protein kinase turns on and maintains the activity of MAP kinase, but not MPF, in cell‐free extracts of Xenopus oocytes and eggs. , 1993, The EMBO journal.

[8]  Jonathan A. Cooper,et al.  Mos stimulates MAP kinase in Xenopus oocytes and activates a MAP kinase kinase in vitro , 1993, Molecular and cellular biology.

[9]  G. V. Vande Woude,et al.  Characterization of activated and normal mouse Mos gene in murine 3T3 cells. , 1992, Oncogene.

[10]  R. Erikson,et al.  Activation of protein serine/threonine kinases p42, p63, and p87 in Rous sarcoma virus-transformed cells: signal transduction/transformation-dependent MBP kinases. , 1992, Molecular biology of the cell.

[11]  E. Nishida,et al.  Regulation of a major microtubule‐associated protein by MPF and MAP kinase. , 1992, The EMBO journal.

[12]  G. V. Vande Woude,et al.  pp39mos is associated with p34cdc2 kinase in c-mosxe-transformed NIH 3T3 cells , 1992, Molecular and cellular biology.

[13]  K. Okazaki,et al.  The ‘second‐codon rule’ and autophosphorylation govern the stability and activity of Mos during the meiotic cell cycle in Xenopus oocytes. , 1992, The EMBO journal.

[14]  H. Joshi,et al.  γ-Tubulin is a centrosomal protein required for cell cycle-dependent microtubule nucleation , 1992, Nature.

[15]  G. Woude,et al.  Meiotic initiation by the mos protein in Xenopus , 1992, Nature.

[16]  L. Ramagli,et al.  The physical interactions between p37env-mos and tubulin structures. , 1992, Oncogene.

[17]  G. Borisy,et al.  Specific association of an M-phase kinase with isolated mitotic spindles and identification of two of its substrates as MAP4 and MAP1B. , 1991, Cell regulation.

[18]  M. Meistrich,et al.  Linkage of manchette microtubules to the nuclear envelope and observations of the role of the manchette in nuclear shaping during spermiogenesis in rodents. , 1991, The American journal of anatomy.

[19]  T. Hunter,et al.  Human cyclins A and B1 are differentially located in the cell and undergo cell cycle-dependent nuclear transport , 1991, The Journal of cell biology.

[20]  R. Arlinghaus,et al.  Inhibition of c-mos protein kinase blocks mouse zygotes at the pronuclei stage. , 1991, Oncogene.

[21]  G. Cooper,et al.  The c-mos gene product is required for cyclin B accumulation during meiosis of mouse eggs. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[22]  T. Hunt,et al.  Xenopus oocyte maturation does not require new cyclin synthesis , 1991, The Journal of cell biology.

[23]  T. Hunt,et al.  On the synthesis and destruction of A- and B-type cyclins during oogenesis and meiotic maturation in Xenopus laevis , 1991, The Journal of cell biology.

[24]  Yixian Zheng,et al.  γ-Tubulin is present in Drosophila melanogaster and homo sapiens and is associated with the centrosome , 1991, Cell.

[25]  M. Kirschner,et al.  γ-Tubulin is a highly conserved component of the centrosome , 1991, Cell.

[26]  G. Saunders,et al.  A novel M phase-specific H1 kinase recognized by the mitosis-specific monoclonal antibody MPM-2. , 1991, Developmental biology.

[27]  D. Donoghue,et al.  Meiotic induction by Xenopus cyclin B is accelerated by coexpression with mosXe , 1991, Molecular and cellular biology.

[28]  G. V. Vande Woude,et al.  Ability of the c-mos product to associate with and phosphorylate tubulin. , 1991, Science.

[29]  X. Zhao,et al.  The role of c-mos proto-oncoprotein in mammalian meiotic maturation. , 1991, Oncogene.

[30]  G. V. Vande Woude,et al.  mos gene transforming efficiencies correlate with oocyte maturation and cytostatic factor activities , 1991, Molecular and cellular biology.

[31]  E. Nishida,et al.  In vitro effects on microtubule dynamics of purified Xenopus M phase-activated MAP kinase , 1991, Nature.

[32]  J. Maller,et al.  Cyclin B in Xenopus oocytes: implications for the mechanism of pre‐MPF activation. , 1991, The EMBO journal.

[33]  G. V. Vande Woude,et al.  Neuropathological changes in transgenic mice carrying copies of a transcriptionally activated Mos protooncogene , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[34]  D. Donoghue,et al.  Effects of the v-mos oncogene on Xenopus development: meiotic induction in oocytes and mitotic arrest in cleaving embryos , 1990, The Journal of cell biology.

[35]  J. Maller,et al.  The cyclin B2 component of MPF is a substrate for the c-mosxe proto-oncogene product , 1990, Cell.

[36]  M. Simon,et al.  Developmental regulation of expression of the lactate dehydrogenase ( LDH ) multigene family during mouse spermatogenesis , 2005 .

[37]  Y. Masamune,et al.  Transcription switch of two phosphoglycerate kinase genes during spermatogenesis as determined with mouse testis sections in situ. , 1990, Experimental cell research.

[38]  Eric Karsenti,et al.  Regulation of microtubule dynamics by cdc2 protein kinase in cell-free extracts of Xenopus eggs , 1990, Nature.

[39]  Yun-Fai Chris Lau,et al.  Stage‐Specific expression of the lactate dehydrogenase‐X gene in adult and developing mouse testes , 1990, Molecular reproduction and development.

[40]  E. Goldberg Developmental expression of lactate dehydrogenase isozymes during spermatogenesis. , 1990, Progress in clinical and biological research.

[41]  G. Woude,et al.  The c-mos proto-oncogene product is a cytostatic factor responsible for meiotic arrest in vertebrate eggs , 1989, Nature.

[42]  M. Simon,et al.  Transcriptional regulatory regions of testis-specific PGK2 defined in transgenic mice. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[43]  G. Cooper,et al.  Microinjection of antisense c-mos oligonucleotides prevents meiosis II in the maturing mouse egg. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[44]  G. V. Vande Woude,et al.  The product of the mos proto-oncogene as a candidate "initiator" for oocyte maturation. , 1989, Science.

[45]  D. Donoghue,et al.  Xenopus homolog of the mos protooncogene transforms mammalian fibroblasts and induces maturation of Xenopus oocytes. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[46]  G. Saunders,et al.  Mitosis-specific monoclonal antibody MPM-2 inhibits Xenopus oocyte maturation and depletes maturation-promoting activity. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[47]  G. V. Vande Woude,et al.  Mouse Mos protooncogene product is present and functions during oogenesis. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[48]  L. Adams,et al.  Increased amount of a 25-kilodalton phosphoprotein after v-mos transfection of CHO cells , 1988, Molecular and cellular biology.

[49]  G. Woude,et al.  Function of c-mos proto-oncogene product in meiotic maturation in Xenopus oocytes , 1988, Nature.

[50]  H. Zimmermann,et al.  Identification of the phosphorylated β‐tubulin isotype in differentiated neuroblastoma cells , 1988, FEBS letters.

[51]  N. Copeland,et al.  Genetic analysis and developmental regulation of testis-specific RNA expression of Mos, Abl, actin and Hox-1.4. , 1988, Oncogene.

[52]  D. Wolgemuth,et al.  Evidence for the involvement of the proto‐oncogene c‐mos in mammalian meiotic maturation and possibly very early embryogenesis. , 1988, The EMBO journal.

[53]  N. Copeland,et al.  Developmental regulation of ovarian-specific Mos expression. , 1988, Oncogene.

[54]  D. Wolgemuth,et al.  Distinct developmental patterns of c-mos protooncogene expression in female and male mouse germ cells. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[55]  G. Cooper,et al.  Expression of c-mos RNA in germ cells of male and female mice. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[56]  J. McCarrey Nucleotide sequence of the promoter region of a tissue-specific human retroposon: comparison with its housekeeping progenitor. , 1987, Gene.

[57]  M. Handel Genetic control of spermatogenesis in mice. , 1987, Results and problems in cell differentiation.

[58]  M. Tainsky,et al.  Analysis of the transforming potential of the human homolog of mos , 1986, Cell.

[59]  G. Borisy,et al.  Phosphoproteins are components of mitotic microtubule organizing centers. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[60]  K. Grzeschik,et al.  A human autosomal phosphoglycerate kinase locus maps near the HLA cluster. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[61]  F. M. Davis,et al.  Monoclonal antibodies to mitotic cells. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[62]  W. Mcclements,et al.  Activation of the transforming potential of a normal cell sequence: a molecular model for oncogenesis. , 1981, Science.

[63]  S. Berkowitz,et al.  Separation and characterization of microtubule proteins from calf brain. , 1977, Biochemistry.

[64]  Katharina Wagner,et al.  Reproduction of Mammals , 1965, Nature.

[65]  E. Oakberg Duration of spermatogenesis in the mouse and timing of stages of the cycle of the seminiferous epithelium. , 1956, The American journal of anatomy.