Skip to main content
SpringerLink
Log in

Guide to Techniques in Creating Transgenic Mouse Models Using SV40 T Antigen

  • Protocol
SV40 Protocols

Part of the book series: Methods in Molecular Biology™ ((MIMB,volume 165))

  • 527 Accesses

Abstract

The experimental introduction of foreign DNA into the germ line of a mouse is a powerful tool used to identify genetic elements required for appropriate tissue expression, to determine the developmental specificity of gene expression and to determine the consequences of inappropriate expression of cellular oncogenes. Moreover, by fusing a tissue-specific regulatory region of a particular gene to transforming genes, it is possible to direct expression of the transforming gene to specific cell types, thereby producing lines of mice that develop tumors in specific organs. Transgenic mice may then serve as useful models to study the multistage development of certain diseases such as cancer and may also be used to test various types of therapies for treatment of these diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Ludlow, J. W. (1993) Interactions between SV40 large-tumor antigen and the growth suppressor proteins pRB and p53. FASEB J. 7, 866–871.

    CAS  PubMed  Google Scholar 

  2. Fromm, L., Shawlot, W., Gunning, K., Butel., S. S., and Overbeek, P. A. (1994) The retinoblastoma protein-binding region of simian virus 40 large T antigen alters cell cycle regulation in lenses of transgenic mice. Mol. Cell. Biol. 14, 6743–6754.

    CAS  PubMed  Google Scholar 

  3. Brinster, R. L., Chen, H. Y., Messing, A., vanDyke, T., Levine, A. J., and Palmiter, R. D. (1984) Transgenic mice harboring SV40 T-antigen genes develop characteristic brain tumors. Cell 37, 367–379.

    Article  CAS  PubMed  Google Scholar 

  4. Hanahan, D. (1985) Heritable formation of pancreatic beta-cell tumours in transgenic mice expressing recombinant insulin/simian virus 40 oncogenes. Nature 315, 115–122.

    Article  CAS  PubMed  Google Scholar 

  5. Messing, A., Chen, H. Y., Palmiter, R. D., and Brinster, R. L. (1985) Peripheral neuropathies, hepatocellular carcinomas and islet cell adenomas in transgenic mice. Nature 16, 461–463.

    Article  Google Scholar 

  6. Ornitz, D. M., Hammer, R. E., Messing, A., Palmiter, R. D., and Brinster, R. L. (1987) Pancreatic neoplasia induced by SV40 T-antigen expression in acinar cells of transgenic mice. Science 238, 188–193.

    Article  CAS  PubMed  Google Scholar 

  7. Mahon, K. A., Chepelinsky, A. B., Khillan, J. S., Overbeek, P. A., Piatigorsky, J., and Westphal, H. (1987) Oncogenesis of the lens in transgenic mice. Science 235, 1622–1628.

    Article  CAS  PubMed  Google Scholar 

  8. Murphy, D., Bishop, A., Rindi, G., Murphy, M. N., Stamp, G. W., Hanson, J., Polak, J. M., and Hogan, B. (1987) Mice transgenic for a vasopressin-SV40 hybrid oncogene develop tumors of the endocrine pancreas and the anterior pituitary. A possible model for human multiple endocrine neoplasia type 1. Am. J. Pathol. 129, 552–566.

    CAS  PubMed  Google Scholar 

  9. Choi, Y. W., Henrard, D., Lee, I., and Ross, S. R. (1987) The mouse mammary tumor virus long terminal repeat directs expression in epithelial and lymphoid cells of different tissues in transgenic mice. J. Virol. 61, 3013–3019.

    CAS  PubMed  Google Scholar 

  10. Behringer, R. R., Peschon, J. J., Messing, A., Gartside, C. L., Hauschka, S. D., Palmiter, R. D., and Brinster, R. L. (1988) Heart and bone tumors in transgenic mice. Proc. Natl. Acad. Sci. USA 85, 2648–2652.

    Article  CAS  PubMed  Google Scholar 

  11. Efrat, S., Teitelman, G., Anwar, M., Ruggiero, D., and Hanahan, D. (1988) Glucagon gene regulatory region directs oncoprotein expression to neurons and pancreatic cells. Neuron 1, 605–613.

    Article  CAS  PubMed  Google Scholar 

  12. Baetge, E. E., Behringer, R. R., Messing, A., Brinster, R. L., and Palmiter, R. D. (1988) Transgenic mice express the human phenylethanolamine N-methyltransferase gene in adrenal medulla and retina. Proc. Natl. Acad. Sci. USA 85, 3648–3652.

    Article  CAS  PubMed  Google Scholar 

  13. Field, L. (1988) Atrial natriuretic factor-SV40 T antigen transgenes produce tumors and cardiac arrhythmias in mice. Science 239, 1029–1033.

    Article  CAS  PubMed  Google Scholar 

  14. Sola, C., Tronik, D., Dreyfus, M., Babinet, C., and Rougeon, F. (1989) Reninpromoter SV40 large T-antigen transgenes induce tumors irrespective of normal cellular expression of renin genes. Oncogene Res. 5, 149–153.

    CAS  PubMed  Google Scholar 

  15. Sepulveda, A. R., Finegold, M. J., Smith, B., Slagle, B. L., DeMayo, J. L., Shen, R. F., Woo, S. L., and Butel, J. S. (1989) Development of a transgenic mouse system for the analysis of stages in liver carcinogenesis using tissue-specific expression of SV40 large T-antigen controlled by regulatory elements of the human alpha-1-antitrypsin genes. Cancer Res. 49, 6108–6117.

    CAS  PubMed  Google Scholar 

  16. Held, W. A., Mullins, J. J., Kuhn, N. J., Gallagher, J. F., Gu, G. D., and Gross, K. W. (1989) T antigen expression and tumorigenesis in transgenic mice containing a mouse major urinary protein/SV40 T antigen hybrid gene. EMBO J. 8, 183–191.

    CAS  PubMed  Google Scholar 

  17. Mellon, P. L., Windle, J. J., Goldsmith, P. C., Padula, C. A., Roberts, J. L., and Weiner, R. I. (1990) Immortalization of hypothalamic GnRH neurons by genetically targeted tumorigenesis. Neuron 5, 1–10.

    Article  CAS  PubMed  Google Scholar 

  18. Theuring, F., Gotz, W., Balling, R., Korf, H. W., Schulze, F., Herken, R., and Gruss, P. (1990) Tumorigenesis and eye abnormalities in transgenic mice expressing MSV-SV40 large T-antigen. Oncogene 5, 225–232.

    CAS  PubMed  Google Scholar 

  19. Windle, J. J., Weiner, R. I., and Mellon, P. L. (1990) Cell lines of the pituitary gonadotrope lineage derived by targeted oncogenesis in transgenic mice. Mol. Endocrinol. 4, 597–603.

    Article  CAS  PubMed  Google Scholar 

  20. Windle, J. J., Albert, D. M., O’Brien, J. M., Marcus, D. M., Disteche, C. M., Bernards, R., and Mellon, P. L. (1990) Retinoblastoma in transgenic mice. Nature 343, 665–669.

    Article  CAS  PubMed  Google Scholar 

  21. Skowronski, J. (1991) Expression of a human immunodeficiency virus type 1 long terminal repeat/simian virus 40 early region fusion gene in transgenic mice. J. Virol. 65, 754–762.

    CAS  PubMed  Google Scholar 

  22. Skalnik, D. G., Dorfman, D. M., Perkins, A. S., Jenkins, N. A., Copeland, N. G., and Orkin, S. H. (1991) Targeting of transgene expression to monocyte/macrophages by the gp91-phox promoter and consequent histiocytic malignancies. Proc. Natl. Acad. Sci. USA 88, 8505–8509.

    Article  CAS  PubMed  Google Scholar 

  23. Kitagawa, T., Hino, O., Lee, G. H., Li, H., Liu, J., Nomura, K., Ohtake, K., Furuta, Y., and Aizawa, S. (1991) Multistep hepatocarcinogenesis in transgenic mice harboring SV40 T-antigen gene. Princess Takamatsu Symp. 22, 349–360.

    CAS  PubMed  Google Scholar 

  24. Ledent, C., Dumont, J., Vassart, G., and Parmentier, M. (1991) Thyroid adenocarcinomas secondary to tissue-specific expression of simian virus-40 large T-antigen in transgenic mice. Endocrinology 129, 1391–1401.

    Article  CAS  PubMed  Google Scholar 

  25. Katz, E. B., Steinhelper, M. E., Delcarpio, J. B., Daud, A. I., Claycomb, W. C., and Field, L. J. (1992) Cardiomyocyte proliferation in mice expressing-cardiac myosin heavy chain-SV40 T-antigen transgenes. Am. J. Physiol. 262, H1867–H1876.

    CAS  PubMed  Google Scholar 

  26. Wikenheiser, K. A., Clark, J. C., Linnoila, R. I., Stahlman, M. T., and Whitsett, J. A. (1992) Simian virus 40 large T antigen directed by transcriptional elements of the human surfactant protein C gene produces pulmonary adenocarcinomas in transgenic mice. Cancer Res. 52,19), 5342–5352.

    CAS  PubMed  Google Scholar 

  27. Perraud, F., Yoshimura, K., Louis, B., Dalemans, W., Ali-Hadji, D., Schultz, H., Claudepierre, M. C., Chartier, C., Danel, C., and Bellocq, J. P. (1992) The promoter of the human cystic fibrosis transmembrane conductance regulator gene directing SV40 T antigen expression induces malignant proliferation of ependymal cells in transgenic mice. Oncogene 7, 993–997.

    CAS  PubMed  Google Scholar 

  28. Al-Ubaidi, M. R., Hollyfield, J. G., Overbeek, P. A., and Baehr, W. (1992) Photoreceptor degeneration induced by the expression of simian virus 40 large tumor antigen in the retina of transgenic mice. Proc. Natl. Acad. Sci. USA 89, 1194–1198.

    Article  CAS  PubMed  Google Scholar 

  29. Brubaker, P. L., Lee, Y. C., and Drucker, D. J. (1992) Alterations in proglucagon processing and inhibition of proglucagon gene expression in transgenic mice which contain a chimeric proglucagon-SV40 T antigen gene. J. Biol. Chem. 267, 20,728–20,733.

    CAS  PubMed  Google Scholar 

  30. Lew, D., Brady, H., Klausing, K., Yaginuma, K., Theill, L. E., Stauber, C., Karin, M., and Mellon, P. L. (1993) GHF-1-promoter-targeted immortalization of a somatotropic progenitor cell results in dwarfism in transgenic mice. Genes Dev. 7, 783–793.

    Article  Google Scholar 

  31. Low, M. J., Liu, B., Hammer, G. D., Rubinstein, M., and Allen, R. G. (1993) Posttranslational processing of proopiomelanocortin (POMC) in mouse pituitary melanotroph tumors induced by a POMC-simian virus 40 large T antigen transgene. J. Biol. Chem. 268, 24,967–24,975.

    CAS  PubMed  Google Scholar 

  32. Jensen, N. A., Rodriguez, M. L., Garvey, J. S., Miller, C. A., and Hood, L. (1993) Transgenic mouse model for neurocristopathy: Schwannomas and facial bone tumors. Proc. Natl. Acad. Sci. USA 90, 3192–3196.

    Article  CAS  PubMed  Google Scholar 

  33. Tzeng, Y. J., Guhl, E., Graessmann, M., and Graessmann, A. (1993) Breast cancer formation in transgenic animals induced by the whey acidic protein SV40 T antigen (WAP-SV-T) hybrid gene. Oncogene 8, 1965–1971.

    CAS  PubMed  Google Scholar 

  34. Bryce, D. M., Liu, Q., Khoo, W., Tsui, L. C., and Breitman, M. L. (1993) Progressive and regressive fate of lens tumors correlates with subtle differences in transgene expression in gamma F-crystallin-SV40 T antigen transgenic mice. Oncogene 8, 1611–1620.

    CAS  PubMed  Google Scholar 

  35. Maroulakou, I., Anver, M., Garrett, L., and Green, J. E. (1994) Prostate and mammary adenocarcinoma in transgenic mice carrying a rat C3(1) simian virus 40 large tumor antigen fusion gene. Proc. Natl. Acad. Sci. USA 91, 11,236–11,240.

    Article  CAS  PubMed  Google Scholar 

  36. Maki, K., Miyoshi, I., Kon, Y., Yamashita, T., Sasaki, N., Aoyama, S., Takahaski, E., Namioka, S., Hayashizaki, Y., and Kasai, N. (1994) Targeted pituitary tumorigenesis using the human thyrotropin-subunit chain promoter in transgenic mice. Mol. Cell. Endocrinol. 105, 147–154.

    Article  CAS  PubMed  Google Scholar 

  37. Giraldi, F. P., Mizobuchi, M., Horowitz, Z. D., Downs, T. R., Aleppo, G., Kier, A., Wagner, T., Yun, J. S., Kopchick, J. J., and Frohman, L. A. (1994) Development of neuroepithelial tumors of the adrenal medulla in transgenic mice expressing a mouse hypothalamic growth hormone-releasing hormone promoter-simian virus-40 T-antigen fusion gene. Endocrinology 134, 1219–1224.

    Article  CAS  Google Scholar 

  38. Pascall, I. C., Surani, M. A., Barton, S. C., Vaughan, T. J., and Brown, K. D. (1994) Directed expression of simian virus 40 T-antigen in transgenic mice using the epidermal growth factor gene promoter. J. Mol. Endocrinol. 12, 313–325.

    Article  CAS  PubMed  Google Scholar 

  39. Danks, R. A., Orian, J. M., Gonzales, M. F., Tan, S. S., Alexander, B., Mikoshiba, K., and Kaye, A. H. (1995) Transformation of astrocytes in transgenic mice expressing SV40 T antigen under the transcriptional control of the glial fibrillary acidic protein promoter. Cancer Res. 55, 4302–4310.

    CAS  PubMed  Google Scholar 

  40. Cheah, K. S., Levy, A., Trainor, P. A., Wai, A. W., Kuffner, T., So, C. L., Leung, K. K., Lovell-Badge, R. H., and Tam, P. P. (1995) Human COL2A1-directed SV40 T antigen expression in transgenic and chimeric mice results in abnormal skeletal development. J. Cell. Biol. 128, 223–237.

    Article  CAS  PubMed  Google Scholar 

  41. Kananen, K., Markkula, M., Rainio, E., Su, J. G., Hsueh, A. J., and Huhtaniemi, I. T. (1995) Gonadal tumorigenesis in transgenic mice bearing the mouse inhibin alphasubunit promoter/simian virus T-antigen fusion gene: characterization of ovarian tumors and establishment of gonadotropin-responsive granulosa cell lines. Mol. Endocrinol. 9, 616–627.

    Article  CAS  PubMed  Google Scholar 

  42. Greenberg, N. M., DeMayo, F., Finegold, M. J., Medina, D., Tilley, W. D., Aspinall, J. O., Cunha, G. R., Donjacour, A. A., Matusik, R. J., and Rosen, J. M. (1995) Prostate cancer in a transgenic mouse. Proc. Natl. Acad. Sci. USA 92, 3439–3443.

    Article  CAS  PubMed  Google Scholar 

  43. Sandmoller, A., Halter, R., Suske, G., Paul, D., and Beato, M. (1995) A transgenic mouse model for lung adenocarcinoma. Cell Growth Differ. 6, 97–103.

    CAS  PubMed  Google Scholar 

  44. Park, W. Y., Kim, J. I., Shim, E. H., Lee, W. H., Kim, S. H., Seo, J. W., Jang, J. J., and Seo, J. S. (1996) Development of thymic carcinoma in transgenic mice expression SV40 T antigen. Cancer Lett. 107, 293–300.

    Article  CAS  PubMed  Google Scholar 

  45. Bosse, P., Bernex, F., De Sepulveda, P., Salaun, P., and Panthier, J. J. (1997) Multiple neuroendocrine tumours in transgenic mice induced by c-kit SV40 T antigen fusion genes. Oncogene 14, 2661–2670.

    Article  CAS  PubMed  Google Scholar 

  46. Penna, D., Schmidt, A., and Beermann, F. (1998) Tumors of the retinal pigment epithelium metastasize to inguinal lymph nodes and spleen in tyrosinase-related protein 1/SV40 T antigen transgenic mice. Oncogene 17, 2601–2607.

    Article  CAS  PubMed  Google Scholar 

  47. Nogues, N., Magnan, E., DeGrandis, P., Butz, M., Kineman, R. D., Kopchick, J. J., and Frohman, L. A. (1998) Expression of a fusion gene consisting for the mouse growth hormone-releasing hormone gene promoter linked to the SV40 T-antigen gene in transgenic mice. Mol. Cell. Endocrinol. 137, 161–168.

    Article  CAS  PubMed  Google Scholar 

  48. Garabedian, E. M., Humphrey, P. A., and Gordon, J. I. (1998) A transgenic mouse model of metastatic prostate cancer originating from neuroendocrine cells. Proc. Natl. Acad. Sci. USA 95, 15,382–15,387.

    Article  CAS  PubMed  Google Scholar 

  49. Hurst, H. C. and Parker, M. G. (1983) Rat prostatic steroid binding protein: DNA sequence and transcript maps of the two C3 genes. EMBO J. 2, 769–774.

    CAS  PubMed  Google Scholar 

  50. Sambrook, J., Fritsch, E. F., and Maniatis, T. (1989) Molecular Cloning, A Laboratory Manual, 2nd ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.

    Google Scholar 

  51. Hogan, B., Costantini, F., and Lacy, E. (1986) Manipulating the Mouse Embryo, A Laboratory Manual (Cuddihy, J., ed.), Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Center for Molecular and Structural Biology, Medical University of South Carolina, Charleston, SC

    Ioanna G. Maroulakou

  2. Department of Biology, Center for Molecular and Structural Biology, Medical University of South Carolina, Charleston, SC

    Robin C. Muise-Helmericks

Authors
  1. Ioanna G. Maroulakou
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Robin C. Muise-Helmericks
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Queen’s University, Kingston, Ontario, Canada

    Leda Raptis

Rights and permissions

Reprints and permissions

Copyright information

© 2001 Humana Press Inc., Totowa, NJ

About this protocol

Cite this protocol

Maroulakou, I.G., Muise-Helmericks, R.C. (2001). Guide to Techniques in Creating Transgenic Mouse Models Using SV40 T Antigen. In: Raptis, L. (eds) SV40 Protocols. Methods in Molecular Biology™, vol 165. Humana Press. https://doi.org/10.1385/1-59259-117-5:269

Download citation

  • DOI: https://doi.org/10.1385/1-59259-117-5:269

  • Publisher Name: Humana Press

  • Print ISBN: 978-0-89603-653-6

  • Online ISBN: 978-1-59259-117-6

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation