Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1987 Oct;61(10):3013–3019. doi: 10.1128/jvi.61.10.3013-3019.1987

The mouse mammary tumor virus long terminal repeat directs expression in epithelial and lymphoid cells of different tissues in transgenic mice.

Y W Choi, D Henrard, I Lee, S R Ross
PMCID: PMC255874  PMID: 3041021

Abstract

A series of transgenic mice was developed that contained the simian virus 40 early region genes under the transcriptional control of the mouse mammary tumor virus long terminal repeat, including the promoter and glucocorticoid response elements. These mice all expressed the transgene in the epithelial cells of a number of different organs, such as lungs, kidneys, and prostate, salivary, and mammary glands, and in Leydig and lymphoid cells. Transcription of the chimeric gene was inducible by glucocorticoids, either after transfection into tissue culture cells or in cells cultured from animals carrying the transgene. Many, but not all, tissues which expressed the simian virus 40 sequences, as determined immunologically and by RNA analysis, developed into tumors, although they showed premalignant features. Since the mouse mammary tumor virus long terminal repeat is expressed in a number of different cell types when inherited through the germ line, the lactating mammary gland-specific transcription of endogenous proviruses must require other factors or sequences to achieve this specificity.

Full text

PDF
3013

Images in this article

3015Image
on p.3015
3016Image
on p.3016
3017Image
on p.3017
3017Image
on p.3017
3018Image
on p.3018

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Birnboim H. C., Doly J. A rapid alkaline extraction procedure for screening recombinant plasmid DNA. Nucleic Acids Res. 1979 Nov 24;7(6):1513–1523. doi: 10.1093/nar/7.6.1513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Brinster R. L., Chen H. Y., Messing A., van Dyke T., Levine A. J., Palmiter R. D. Transgenic mice harboring SV40 T-antigen genes develop characteristic brain tumors. Cell. 1984 Jun;37(2):367–379. doi: 10.1016/0092-8674(84)90367-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  4. Dickson C., Smith R., Brookes S., Peters G. Tumorigenesis by mouse mammary tumor virus: proviral activation of a cellular gene in the common integration region int-2. Cell. 1984 Jun;37(2):529–536. doi: 10.1016/0092-8674(84)90383-0. [DOI] [PubMed] [Google Scholar]
  5. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  6. Hammer R. E., Krumlauf R., Camper S. A., Brinster R. L., Tilghman S. M. Diversity of alpha-fetoprotein gene expression in mice is generated by a combination of separate enhancer elements. Science. 1987 Jan 2;235(4784):53–58. doi: 10.1126/science.2432657. [DOI] [PubMed] [Google Scholar]
  7. Hanahan D. Heritable formation of pancreatic beta-cell tumours in transgenic mice expressing recombinant insulin/simian virus 40 oncogenes. Nature. 1985 May 9;315(6015):115–122. doi: 10.1038/315115a0. [DOI] [PubMed] [Google Scholar]
  8. Hu W. S., Fanning T. G., Cardiff R. D. Mouse mammary tumor virus: specific methylation patterns of proviral DNA in normal mouse tissues. J Virol. 1984 Jan;49(1):66–71. doi: 10.1128/jvi.49.1.66-71.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Imai S., Morimoto J., Tsubura Y., Iwai Y., Okumoto M., Takamori Y., Tsubura A., Hilgers J. Tissue and organ distribution of mammary tumor virus antigens in low and high mammary cancer strain mice. Eur J Cancer Clin Oncol. 1983 Jul;19(7):1011–1019. doi: 10.1016/0277-5379(83)90071-8. [DOI] [PubMed] [Google Scholar]
  10. Leder A., Pattengale P. K., Kuo A., Stewart T. A., Leder P. Consequences of widespread deregulation of the c-myc gene in transgenic mice: multiple neoplasms and normal development. Cell. 1986 May 23;45(4):485–495. doi: 10.1016/0092-8674(86)90280-1. [DOI] [PubMed] [Google Scholar]
  11. Lehrach H., Diamond D., Wozney J. M., Boedtker H. RNA molecular weight determinations by gel electrophoresis under denaturing conditions, a critical reexamination. Biochemistry. 1977 Oct 18;16(21):4743–4751. doi: 10.1021/bi00640a033. [DOI] [PubMed] [Google Scholar]
  12. Lopez D. M., Charyulu V., Paul R. D. B cell subsets in spleens of BALB/c mice: identification and isolation of MMTV-expressing and MMTV-responding subpopulations. J Immunol. 1985 Jan;134(1):603–607. [PubMed] [Google Scholar]
  13. Majors J., Varmus H. E. A small region of the mouse mammary tumor virus long terminal repeat confers glucocorticoid hormone regulation on a linked heterologous gene. Proc Natl Acad Sci U S A. 1983 Oct;80(19):5866–5870. doi: 10.1073/pnas.80.19.5866. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Marcus S. L., Smith S. W., Sarkar N. H. Quantitative of murine mammary tumor virus-related RNA in mammary tissues of low- and high-mammary-tumor-incidence mouse strains. J Virol. 1981 Oct;40(1):87–95. doi: 10.1128/jvi.40.1.87-95.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Michalides R., Wagenaar E., Weijers P. Rearrangements in the long terminal repeat of extra mouse mammary tumor proviruses in T-cell leukemias of mouse strain GR result in a novel enhancer-like structure. Mol Cell Biol. 1985 Apr;5(4):823–830. doi: 10.1128/mcb.5.4.823. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Moore R., Casey G., Brookes S., Dixon M., Peters G., Dickson C. Sequence, topography and protein coding potential of mouse int-2: a putative oncogene activated by mouse mammary tumour virus. EMBO J. 1986 May;5(5):919–924. doi: 10.1002/j.1460-2075.1986.tb04304.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Nusse R., Varmus H. E. Many tumors induced by the mouse mammary tumor virus contain a provirus integrated in the same region of the host genome. Cell. 1982 Nov;31(1):99–109. doi: 10.1016/0092-8674(82)90409-3. [DOI] [PubMed] [Google Scholar]
  18. Nusse R., van Ooyen A., Cox D., Fung Y. K., Varmus H. Mode of proviral activation of a putative mammary oncogene (int-1) on mouse chromosome 15. Nature. 1984 Jan 12;307(5947):131–136. doi: 10.1038/307131a0. [DOI] [PubMed] [Google Scholar]
  19. Ornitz D. M., Palmiter R. D., Messing A., Hammer R. E., Pinkert C. A., Brinster R. L. Elastase I promoter directs expression of human growth hormone and SV40 T antigen genes to pancreatic acinar cells in transgenic mice. Cold Spring Harb Symp Quant Biol. 1985;50:399–409. doi: 10.1101/sqb.1985.050.01.050. [DOI] [PubMed] [Google Scholar]
  20. Overbeek P. A., Lai S. P., Van Quill K. R., Westphal H. Tissue-specific expression in transgenic mice of a fused gene containing RSV terminal sequences. Science. 1986 Mar 28;231(4745):1574–1577. doi: 10.1126/science.3006249. [DOI] [PubMed] [Google Scholar]
  21. Palmiter R. D., Brinster R. L. Germ-line transformation of mice. Annu Rev Genet. 1986;20:465–499. doi: 10.1146/annurev.ge.20.120186.002341. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Palmiter R. D., Chen H. Y., Messing A., Brinster R. L. SV40 enhancer and large-T antigen are instrumental in development of choroid plexus tumours in transgenic mice. Nature. 1985 Aug 1;316(6027):457–460. doi: 10.1038/316457a0. [DOI] [PubMed] [Google Scholar]
  23. Payvar F., DeFranco D., Firestone G. L., Edgar B., Wrange O., Okret S., Gustafsson J. A., Yamamoto K. R. Sequence-specific binding of glucocorticoid receptor to MTV DNA at sites within and upstream of the transcribed region. Cell. 1983 Dec;35(2 Pt 1):381–392. doi: 10.1016/0092-8674(83)90171-x. [DOI] [PubMed] [Google Scholar]
  24. Peters G., Lee A. E., Dickson C. Concerted activation of two potential proto-oncogenes in carcinomas induced by mouse mammary tumour virus. Nature. 1986 Apr 17;320(6063):628–631. doi: 10.1038/320628a0. [DOI] [PubMed] [Google Scholar]
  25. Rigby P. W., Dieckmann M., Rhodes C., Berg P. Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol. 1977 Jun 15;113(1):237–251. doi: 10.1016/0022-2836(77)90052-3. [DOI] [PubMed] [Google Scholar]
  26. Rosen C. A., Haseltine W. A., Lenz J., Ruprecht R., Cloyd M. W. Tissue selectivity of murine leukemia virus infection is determined by long terminal repeat sequences. J Virol. 1985 Sep;55(3):862–866. doi: 10.1128/jvi.55.3.862-866.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Ross S. R., Solter D. Glucocorticoid regulation of mouse mammary tumor virus sequences in transgenic mice. Proc Natl Acad Sci U S A. 1985 Sep;82(17):5880–5884. doi: 10.1073/pnas.82.17.5880. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Sarkar A., Günzburg W. H. Spleen specific expression of an MMTV related transcript associated with the Mtv-6 locus in BALB/c mice. Virology. 1986 Oct 15;154(1):233–239. doi: 10.1016/0042-6822(86)90447-2. [DOI] [PubMed] [Google Scholar]
  29. Sodroski J. G., Rosen C. A., Haseltine W. A. Trans-acting transcriptional activation of the long terminal repeat of human T lymphotropic viruses in infected cells. Science. 1984 Jul 27;225(4660):381–385. doi: 10.1126/science.6330891. [DOI] [PubMed] [Google Scholar]
  30. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  31. Stewart T. A., Pattengale P. K., Leder P. Spontaneous mammary adenocarcinomas in transgenic mice that carry and express MTV/myc fusion genes. Cell. 1984 Oct;38(3):627–637. doi: 10.1016/0092-8674(84)90257-5. [DOI] [PubMed] [Google Scholar]
  32. Thomas P. S. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. doi: 10.1073/pnas.77.9.5201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Townes T. M., Chen H. Y., Lingrel J. B., Palmiter R. D., Brinster R. L. Expression of human beta-globin genes in transgenic mice: effects of a flanking metallothionein-human growth hormone fusion gene. Mol Cell Biol. 1985 Aug;5(8):1977–1983. doi: 10.1128/mcb.5.8.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Varmus H. E., Quintrell N., Medeiros E., Bishop J. M., Nowinski R. C., Sarkar N. H. Transcription of mouse mammary tumor virus genes in tissues from high and low tumor incidence mouse strains. J Mol Biol. 1973 Oct 5;79(4):663–679. doi: 10.1016/0022-2836(73)90070-3. [DOI] [PubMed] [Google Scholar]
  35. Wellinger R. J., Garcia M., Vessaz A., Diggelmann H. Exogenous mouse mammary tumor virus proviral DNA isolated from a kidney adenocarcinoma cell line contains alterations in the U3 region of the long terminal repeat. J Virol. 1986 Oct;60(1):1–11. doi: 10.1128/jvi.60.1.1-11.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Yamamoto K. R. Steroid receptor regulated transcription of specific genes and gene networks. Annu Rev Genet. 1985;19:209–252. doi: 10.1146/annurev.ge.19.120185.001233. [DOI] [PubMed] [Google Scholar]
  37. Yoshimura F. K., Davison B., Chaffin K. Murine leukemia virus long terminal repeat sequences can enhance gene activity in a cell-type-specific manner. Mol Cell Biol. 1985 Oct;5(10):2832–2835. doi: 10.1128/mcb.5.10.2832. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES