Home LiteratureArticle Details
PMID: 6327063 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Transgenic mice harboring SV40 T-antigen genes develop characteristic brain tumors.

Cell ·Vol. 37 ·No. 2 ·1984-06-00 ·Pages 367-79

Brinster RL, Chen HY, Messing A, van Dyke T, Levine AJ, Palmiter RD

Abstract

A high percentage of transgenic mice developing from eggs microinjected with plasmids containing the SV40 early region genes and a metallothionein fusion gene develop tumors within the choroid plexus. A line of mice has been established in which nearly every affected animal succumbs to this brain tumor. Thymic hypertrophy and kidney pathology are also observed in some mice. SV40 T-antigen mRNA and protein are readily detected in affected tissues; however, SV40 T-antigen gene expression is barely detectable in unaffected tissues or in susceptible tissues prior to overt pathology, suggesting that tumorigenesis depends upon activation of the SV40 genes. Comparison of DNA from tumor tissue (or cell lines derived from tumors) with DNA from unaffected tissues reveals structural rearrangements as well as changes in DNA methylation of the foreign DNA. The SV40 genes are frequently amplified in tumor tissue, which further indicates that their expression is intimately involved in tumorigenesis in transgenic mice.

MeSH Terms
Animals Antigens, Polyomavirus Transforming Base Sequence Brain Neoplasms/genetics,microbiology Crosses, Genetic DNA Restriction Enzymes Female Genes Genes, Viral Male Mice Nucleic Acid Hybridization Oncogenes Pedigree Plasmids RNA, Messenger/genetics Simian virus 40/genetics Viral Proteins/genetics
Chemicals
Antigens, Polyomavirus Transforming RNA, Messenger Viral Proteins DNA Restriction Enzymes
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Brinster R L
Chen H Y
Messing A
van Dyke T
Levine A J
Palmiter R D
References (50)
50 references, click to expand
  1. Metallothionein-human GH fusion genes stimulate growth of mice.
    Science. 1983 Nov 18;222(4625):809-14 PMID: 6356363
  2. Evidence for non-spliced SV40 RNA in undifferentiated murine teratocarcinoma stem cells.
    Nature. 1979 Jul 26;280(5720):335-8 PMID: 223058
  3. Translocations among antibody genes in human cancer.
    Science. 1983 Nov 18;222(4625):765-71 PMID: 6356357
  4. Cleavage of structural proteins during the assembly of the head of bacteriophage T4.
    Nature. 1970 Aug 15;227(5259):680-5 PMID: 5432063
  5. Somatic expression of herpes thymidine kinase in mice following injection of a fusion gene into eggs.
    Cell. 1981 Nov;27(1 Pt 2):223-31 PMID: 6276022
  6. Expression of a microinjected immunoglobulin gene in the spleen of transgenic mice.
    Nature. 1983 Nov 24-30;306(5941):332-6 PMID: 6417544
  7. Differential regulation of metallothionein-thymidine kinase fusion genes in transgenic mice and their offspring.
    Cell. 1982 Jun;29(2):701-10 PMID: 7116454
  8. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose.
    Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201-5 PMID: 6159641
  9. Independent mechanisms involved in suppression of the Moloney leukemia virus genome during differentiation of murine teratocarcinoma cells.
    Cell. 1983 Apr;32(4):1105-13 PMID: 6188535
  10. Identification of the oncogenic substance in rhesus monkey kidney cell culture as simian virus 40.
    Virology. 1962 May;17:65-75 PMID: 13889129
  11. Adenovirus early region 1A enables viral and cellular transforming genes to transform primary cells in culture.
    Nature. 1983 Aug 18-24;304(5927):602-6 PMID: 6308473
  12. Onc gene amplification in promyelocytic leukaemia cell line HL-60 and primary leukaemic cells of the same patient.
    Nature. 1982 Sep 2;299(5878):61-3 PMID: 6955596
  13. Human-tumor-derived cell lines contain common and different transforming genes.
    Cell. 1981 Dec;27(3 Pt 2):467-76 PMID: 6101201
  14. Transforming activity of human tumor DNAs.
    Proc Natl Acad Sci U S A. 1981 Feb;78(2):1181-4 PMID: 6940134
  15. Expression of the chicken transferrin gene in transgenic mice.
    Cell. 1983 Sep;34(2):335-41 PMID: 6311428
  16. Multiple arrangements of viral DNA and an activated host oncogene in bursal lymphomas.
    Nature. 1982 Jan 21;295(5846):209-14 PMID: 6276760
  17. Incidence, latency, and morphologic types of neoplasms induced by simian virus 40 inoculated intravenously into hamsters of three inbred strains and one outbred stock.
    J Natl Cancer Inst. 1978 Feb;60(2):445-9 PMID: 202720
  18. Two distinct mechanisms regulate the levels of a cellular tumor antigen, p53.
    Mol Cell Biol. 1983 Dec;3(12):2143-50 PMID: 6318085
  19. A cellular oncogene (c-Ki-ras) is amplified, overexpressed, and located within karyotypic abnormalities in mouse adrenocortical tumour cells.
    Nature. 1983 Jun 9-15;303(5917):497-501 PMID: 6304530
  20. Cellular transforming genes.
    Science. 1982 Aug 27;217(4562):801-6 PMID: 6285471
  21. Tumorigenicity of polyoma virus in hamsters.
    Cold Spring Harb Symp Quant Biol. 1980;44 Pt 1,:591-6 PMID: 6253159
  22. Microinjection of cloned retroviral genomes into mouse zygotes: integration and expression in the animal.
    Nature. 1981 Oct 15-21;293(5833):540-2 PMID: 7197324
  23. Sarcomas induced by injection of simian virus 40 into neonatal CFW mice.
    J Natl Cancer Inst. 1979 Oct;63(4):965-8 PMID: 225503
  24. Recovery of DNA segments from agarose gels.
    Anal Biochem. 1980 Jan 15;101(2):339-41 PMID: 6244756
  25. Amplification of endogenous myc-related DNA sequences in a human myeloid leukaemia cell line.
    Nature. 1982 Aug 12;298(5875):679-81 PMID: 6285209
  26. Mutants of SV40 with an altered small t protein are reduced in their ability to transform cells.
    Cell. 1978 May;14(1):79-88 PMID: 208777
  27. Activation of a cellular onc gene by promoter insertion in ALV-induced lymphoid leukosis.
    Nature. 1981 Apr 9;290(5806):475-80 PMID: 6261142
  28. A practical approach for quantitating specific mRNAs by solution hybridization.
    Anal Biochem. 1983 Jun;131(2):385-93 PMID: 6614474
  29. Methylation of the viral genome in an in vitro model of herpes simplex virus latency.
    Proc Natl Acad Sci U S A. 1982 Apr;79(7):2207-10 PMID: 6285373
  30. De novo methylation and expression of retroviral genomes during mouse embryogenesis.
    Nature. 1982 Aug 12;298(5875):623-8 PMID: 6285203
  31. Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes.
    Nature. 1983 Aug 18-24;304(5927):596-602 PMID: 6308472
  32. Neoplastic differentiation: interaction of simian virus 40 and polyoma virus with murine teratocarcinoma cells in vitro.
    J Cell Physiol. 1975 Apr;85(2 Pt 1):179-87 PMID: 164473
  33. Simian virus 40 DNA sequences in DNA of healthy adult mice derived from preimplantation blastocysts injected with viral DNA.
    Proc Natl Acad Sci U S A. 1974 Apr;71(4):1250-4 PMID: 4364530
  34. CELL-TRANSFORMING ABILITY OF A TEMPERATURE-SENSITIVE MUTANT OF POLYOMA VIRUS.
    Proc Natl Acad Sci U S A. 1965 Mar;53:486-91 PMID: 14338226
  35. The human beta-globin gene and a functional viral thymidine kinase gene in developing mice.
    Proc Natl Acad Sci U S A. 1981 Aug;78(8):5016-20 PMID: 6272287
  36. A foreign beta-globin gene in transgenic mice: integration at abnormal chromosomal positions and expression in inappropriate tissues.
    Cell. 1983 Sep;34(2):343-58 PMID: 6616614
  37. 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.
    J Virol. 1984 Feb;49(2):540-8 PMID: 6319753
  38. Leukemia, lymphoma, and osteosarcoma induced in the Syrian golden hamster by simian virus 40.
    Science. 1972 Apr 14;176(4031):173-5 PMID: 4335386
  39. Transforming genes of carcinomas and neuroblastomas introduced into mouse fibroblasts.
    Nature. 1981 Mar 19;290(5803):261-4 PMID: 7207618
  40. Function of simian virus 40 gene A in transforming infection.
    J Virol. 1975 Mar;15(3):613-8 PMID: 163375
  41. The SV40 A gene product is required for the production of a 54,000 MW cellular tumor antigen.
    Virology. 1979 Oct 30;98(2):308-18 PMID: 228475
  42. Fragments of the simian virus 40 transforming gene facilitate transformation of rat embryo cells.
    Proc Natl Acad Sci U S A. 1982 Sep;79(17):5189-93 PMID: 6291029
  43. The induction of ovalbumin and conalbumin mRNA by estrogen and progesterone in chick oviduct explant cultures.
    Cell. 1978 Jun;14(2):403-13 PMID: 566622
  44. Chromatin structure of endogenous retroviral genes and activation by an inhibitor of DNA methylation.
    Nature. 1981 Jul 23;292(5821):311-7 PMID: 6166864
  45. Cellular oncogenes and retroviruses.
    Annu Rev Biochem. 1983;52:301-54 PMID: 6351725
  46. Germ line integration and Mendelian transmission of the exogenous Moloney leukemia virus.
    Proc Natl Acad Sci U S A. 1976 Apr;73(4):1260-4 PMID: 1063407
  47. A simple, rapid, and sensitive DNA assay procedure.
    Anal Biochem. 1980 Mar 1;102(2):344-52 PMID: 6158890
  48. Monoclonal antibodies specific for simian virus 40 tumor antigens.
    J Virol. 1981 Sep;39(3):861-9 PMID: 6169844
  49. "Western blotting": electrophoretic transfer of proteins from sodium dodecyl sulfate--polyacrylamide gels to unmodified nitrocellulose and radiographic detection with antibody and radioiodinated protein A.
    Anal Biochem. 1981 Apr;112(2):195-203 PMID: 6266278
  50. Oncogenes in human tumor cell lines: molecular cloning of a transforming gene from human bladder carcinoma cells.
    Proc Natl Acad Sci U S A. 1982 May;79(9):2845-9 PMID: 6953433
Article Info
Journal
Cell
Abbr.
Cell
ISSN
0092-8674
Published
1984-06-00
Pages
367-79
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC4889224
Subset
IM
Grants
NICHD NIH HHS · R01 HD017321 · United States
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]