Analysis of a transgenic mouse containing simian virus 40 and v-myc sequences

Two plasmids, one containing the simian virus 40 (SV40) genome and the mouse metallothionein I gene and one containing the v-myc gene of avian myelocytomatosis virus MC29, were coinjected into mouse embryos. Of the 13 surviving mice, one, designated M13, contained both myc and SV40 sequences. This mouse developed a cranial bulge identified as a choroid plexus papilloma at 13 weeks and was subsequently sacrificed; tissue samples were taken for further analysis. Primary cell lines derived from these tissues contained both myc and SV40 DNA. No v-myc mRNA could be detected, although SV40 mRNA was present in all of the cell lines tested. T antigen also was expressed in all of the cell lines analyzed. These data suggest that SV40 expression was involved in the abnormalities of mouse M13 and was responsible for the transformed phenotype of the primary cell lines. Primary cell lines from this mouse were atypical in that the population rapidly became progressively more transformed with time in culture based on the following criteria: morphology, growth rate, and the ability to grow in soft agar and in serum-free medium. The data also suggest that factors present in the mouse regulated the ability of SV40 to oncogenically transform most cells and that in vitro culture of cells allowed them to escape those factors.

[1]  P. Leder,et al.  Functional role for c-myc in mitogenic response to platelet-derived growth factor , 1984, Nature.

[2]  R. Palmiter,et al.  Transgenic mice harboring SV40 t-antigen genes develop characteristic brain tumors , 1984, Cell.

[3]  C. Gélinas,et al.  Tumorigenic activity of polyoma virus and SV40 DNAs in newborn rodents. , 1984, Virology.

[4]  I. Verma,et al.  Expression of cellular oncogenes in human malignancies. , 1984, Science.

[5]  B. Diamond,et al.  The generation of macrophage-like cell lines by transfection with SV40 origin defective DNA. , 1984, Journal of immunology.

[6]  G. Maul,et al.  Tumor induction by simian virus 40 in mice is controlled by long-term persistence of the viral genome and the immune response of the host , 1984, Journal of virology.

[7]  J. Sambrook,et al.  Molecular Cloning: A Laboratory Manual , 2001 .

[8]  P. Leder,et al.  Cell-specific regulation of the c-myc gene by lymphocyte mitogens and platelet-derived growth factor , 1983, Cell.

[9]  R. Hammer,et al.  Expression of a microinjected immunoglobulin gene in the spleen of transgenic mice , 1983, Nature.

[10]  P. Leder,et al.  Translocations among antibody genes in human cancer. , 1983, Science.

[11]  R. Hammer,et al.  Expression of the chicken transferrin gene in transgenic mice , 1983, Cell.

[12]  Robert A. Weinberg,et al.  Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes , 1983, Nature.

[13]  R. K. Reynolds,et al.  Nucleotide sequence analysis of the proviral genome of avian myelocytomatosis virus (MC29). , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[14]  D. Mcclure.  Anchorage-independent colony formation of SV40 transformed BALB/c-3T3 cells in serum-free medium: Role of cell- and serum-derived factors , 1983, Cell.

[15]  F. Ruddle,et al.  Gene transfer into mouse embryos: production of transgenic mice by pronuclear injection. , 1983, Methods in enzymology.

[16]  Michael G. Rosenfeld,et al.  Dramatic growth of mice that develop from eggs microinjected with metallothionein–growth hormone fusion genes , 1982, Nature.

[17]  B. Christy,et al.  Expression of transferred thymidine kinase genes is controlled by methylation. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[18]  R. Gallo,et al.  onc gene amplification in promyelocytic leukaemia cell line HL-60 and primary leukaemic cells of the same patient , 1982, Nature.

[19]  R. Weinberg.  Fewer and fewer oncogenes , 1982, Cell.

[20]  R. Palmiter,et al.  Differential regulation of metallothionein-thymidine kinase fusion genes in transgenic mice and their offspring , 1982, Cell.

[21]  R. Palmiter,et al.  Regulation of metallothionein–thymidine kinase fusion plasmids injected into mouse eggs , 1982, Nature.

[22]  D. Hamer,et al.  Regulation in vivo of a cloned mammalian gene: cadmium induces the transcription of a mouse metallothionein gene in SV40 vectors. , 1982, Journal of molecular and applied genetics.

[23]  F. Ruddle,et al.  Integration and stable germ line transmission of genes injected into mouse pronuclei. , 1981, Science.

[24]  R. Palmiter,et al.  Somatic expression of herpes thymidine kinase in mice following injection of a fusion gene into eggs , 1981, Cell.

[25]  E. Wagner,et al.  The human beta-globin gene and a functional viral thymidine kinase gene in developing mice. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[26]  K. Yokoro,et al.  Continuous lines of basophil/mast cells derived from normal mouse bone marrow. , 1981, Science.

[27]  F H Ruddle,et al.  Genetic transformation of mouse embryos by microinjection of purified DNA. , 1980, Proceedings of the National Academy of Sciences of the United States of America.

[28]  P. Thomas,et al.  Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. , 1980, Proceedings of the National Academy of Sciences of the United States of America.

[29]  J. G. Derge,et al.  Comparison of properties of mouse cells transformed spontaneously by ultraviolet light-irradiated herpes simplex virus or by simian virus 40. , 1980, Cancer research.

[30]  P. Duesberg.  Transforming genes of retroviruses. , 1980, Cold Spring Harbor symposia on quantitative biology.

[31]  R. Martin,et al.  Simian virus 40 small t antigen is not required for the maintenance of transformation but may act as a promoter (cocarcinogen) during establishment of transformation in resting rat cells , 1979, Journal of virology.

[32]  W. Rutter,et al.  Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. , 1979, Biochemistry.

[33]  S. Malkiel,et al.  Sarcomas induced by injection of simian virus 40 into neonatal CFW mice. , 1979, Journal of the National Cancer Institute.

[34]  N. Colburn,et al.  Tumour promoter induces anchorage independence irreversibly , 1979, Nature.

[35]  Tom Maniatis,et al.  Transformation of mammalian cells with genes from procaryotes and eucaryotes , 1979, Cell.

[36]  P. Newburger,et al.  Constitutive and inducible granulocyte-macrophage functions in mouse, rat, and human myeloid leukemia-derived continuous tissue culture lines. , 1978, Cancer research.

[37]  G. Sauer.  [Molecular biology of tumor viruses]. , 1977, Die Naturwissenschaften.

[38]  S. Falkow,et al.  General Method for the Isolation of Plasmid Deoxyribonucleic Acid , 1973, Journal of bacteriology.

[39]  V. Defendi,et al.  INFECTION AND TRANSFORMATION OF MOUSE PERITONEAL MACROPHAGES BY SIMIAN VIRUS 40 , 1971, Journal of Experimental Medicine.

[40]  K. Takemoto,et al.  Transformation of Mouse Macrophages by Simian Virus 40 , 1970, Journal of virology.

[41]  R. A. Cox.  [103a] The use of guanidinium chloride in the isolation of nucleic acids , 1968 .