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Regulating Gene Expression in Mammalian Cell Culture and Transgenic Mice with Yeast GAL4/UAS Control Elements

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Book cover Oncogene and Transgenics Correlates of Cancer Risk Assessments

Part of the book series: NATO ASI Series ((NSSA,volume 232))

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Summary

To overcome the difficulties in maintaining strains of mice with decreased reproductive potential due to the expression of toxic genes, we have developed a binary system that will allow one to activate an otherwise silent transgene. This system requires two types of transgenic mice, target strains and transactivator strains. The target strain is engineered to contain a transgene controlled by yeast regulatory sequences that respond only to the yeast transcription factor, GAL4, or a derivative of this protein. The transactivator strains are engineered to express a GAL4 gene that can be driven by any enhancer/promoter combination. In this manuscript we review studies designed to test this binary system in tissue culture cells and in mice. We also discuss several target genes currently being transactivated in mice, and review some of the published data on int-2 expression in GAL4 mice.

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References

  1. Ali, I.U., Merlo, G., Callahan, R., Lidereau, R., (1989) The Amplification Unit on Chromosome 11q13 in Aggressive Primary Human Breast Tumors Entails the bc1–1, int-2 and hst loci. Oncogene 4, 89–92.

    PubMed  CAS  Google Scholar 

  2. Boshart, M., Weber, F., Jahn, G., Dorsch-Hasler, K., Fleckenstein, B., and Schaffner, W., (1985) A Very Strong Enhancer is Located Upstream of an Immediate Early Gene of Human Cytomegalovirus. Cell 41, 521–530.

    Article  PubMed  CAS  Google Scholar 

  3. Byrne, G.W., and Ruddle, F.H., (1989) Multiplex Gene Regulation: A Two-Tiered Approach to Transgene Regulation in Transgenic Mice. Proc. Natl. Acad. Sci. USA 86, 5473–5477.

    Article  PubMed  CAS  Google Scholar 

  4. Dickson, C., Smith, R., Brookes, S., Peters, G., (1984) Tumorigenesis by Mouse Mammary Tumor Virus: Proviral Activation of a Cellular Gene in the Common Integration Region Int-2. Cell 37, 529–536.

    Article  PubMed  CAS  Google Scholar 

  5. Dixon, M., Deed, R., Acland, P., Moore, M., Whyte, A., Peters, G., Dickson, (1989) Detection and Characterization of the Fibroblast Growth Factor-Related Oncoprotein Int-2. Molec. Cell. Biol. 9, 4896–4902.

    CAS  Google Scholar 

  6. Fisher, J.A., Giniger, E., Maniatis, T., Ptashne, M., (1988) GAIA Activates Transcription in Drosophila. Nature 332, 853–856.

    Article  Google Scholar 

  7. Giniger, E., Varnum, S.M., Ptashne, M. (1985) Specific DNA Binding of GAL4, A Positive Regulatory Protein of Yeast. Cell 767–774.

    Google Scholar 

  8. Gorman, C.M., Moffat, L.F., and Howard, B.H., (1982) Recombinant Genomes which Express Chloramphenicol Acetyl Transferase in Mammalian Cells. Molec. Cell. Biol. 2, 1044–1051.

    PubMed  CAS  Google Scholar 

  9. Huang, A. L., Ostrowski, M. C., Berard, D., Hager, G. L., (1981) Glucocorticoid Regulation of the Ha-MuSV p21 gene conferred by sequences from Mouse Mammary Tumor Virus. Cell 27, 245–255.

    Article  PubMed  CAS  Google Scholar 

  10. Jakobovits, A., Shackleford, G. M., Varmus, H. E., Martin, G. R., (1986) Two Proto-Oncogenes Implicated in Mammary Carcinogenesis, Int-1 and Int-2,are Independently Regulated During Mouse Development. Proc. Natl. Acad. Sci. USA 83, 7806–7810.

    Article  PubMed  CAS  Google Scholar 

  11. Kakidani, H., Ptashne, M. (1988) GAL4 Activates Gene Expression in Mammalian Cells. Cell 52, 161–167.

    Article  PubMed  CAS  Google Scholar 

  12. Keegan, L., Gill, G., Ptashne, M., (1986) Separation of DNA Binding from the Transcription-Activating Function of a Eukaryotic Regulatory Protein. Science 231, 699–704.

    Article  PubMed  CAS  Google Scholar 

  13. Khillan, J.S., Deen K.C., Yu, S., Sweet, R.W., Rosenberg, M., Westphal, H. (1988) Gene Transactivation Mediated by the TAT Gene of Human Immunodeficiency Virus in Transgenic Mice. NAR 16, 1423–1430.

    Article  PubMed  CAS  Google Scholar 

  14. Laughon, A., Gesteland, R.E. (1984) Primary structure of the Saccharomyces cerevisiae GALA Gene. Molec. Cell. Biol. 4, 260–267.

    PubMed  CAS  Google Scholar 

  15. Leder, A., Pattengale, P.K., Kuo, A., Stewart, T., Leder, P. (1986) Consequence of Widespread Deregulation of the c-Myc Gene in Transgenic Mice: Multiple Neoplasms and Normal Development. Cell 45, 485–495.

    Article  PubMed  CAS  Google Scholar 

  16. Lidereau, R., Callahan, R., Dickson, C., Peters, G., Escot, C., Ali, I.U. (1988) Amplification of the Int-2 Gene in Primary Human Breast Tumors. Oncogene Res. 2, 285–291.

    PubMed  CAS  Google Scholar 

  17. Ma, J., Przibilla, E., Hu, J., Bogorad, L., Ptashne, M. (1988) Yeast Activators Stimulate Plant Gene Expression. Nature 334, 631–633.

    Article  PubMed  CAS  Google Scholar 

  18. Ma, J., Ptashne, M., (1987) Deletion Analysis of GALA Defines Two Transcriptional Activating Segments. Cell 48, 847–853.

    Article  PubMed  CAS  Google Scholar 

  19. Medina, D. (1973) Preneoplastic Lesions in Mouse Mammary Tumorigenesis. Methods Cancer Res. 7, 3–53.

    CAS  Google Scholar 

  20. Moore, R., Casey, G., Brookes, S., Dixon, M., Peters, G., Dickson, C. (1986) Sequence, Topography and Protein Coding Potential of Mouse Int-2: A Putative Oncogene Activated by Mouse Mammary Tumor Virus. EMBO J. 5, 919–924.

    PubMed  CAS  Google Scholar 

  21. Morris, D.W., Barry, P.A., Bradshaw, H.D. Jr., Cardiff, R.D. (1990) Insertion Mutation of the Int-1 and Int-2 Loci by Mouse Mammary Tumor Virus in Premalignant and Malignant Neoplasms from the GR Mouse Strain. J. Virol. 64, 1794–1802.

    PubMed  CAS  Google Scholar 

  22. Muller, W. J., Lee, F. S., Dickson, C., Peters, G., Pattengale, P., Leder, P (1990) The Int-2 Gene Product Behaves as an Epithelial Growth Factor in Transgenic Mice. EMBO J. 9, 907–913.

    PubMed  CAS  Google Scholar 

  23. Muller, W. J., Sinn, E., Pattengale, P., Wallace, R., Leder, P. (1988) Single-Step Induction of Mammary Adenocarcinoma in Transgenic Mice Bearing an Activated C-Neu Oncogene. Cell 54, 105–115.

    Article  PubMed  CAS  Google Scholar 

  24. Nerenberg, M., Hinrichs, S.H., Reynolds, R.K., Khoury, G., Jay, G. (1987) The TAT Gene of Human T-Lymphotropic Virus Type I Induces Mesenchymal Tumors in Transgenic Mice. Science 237, 1324–1329.

    Article  PubMed  CAS  Google Scholar 

  25. Ornitz, D.M., Hammer, R.E., Davison, B.L., Brinster, R.L., Palmiter, R.D. (1987) Promoter and Enhancer Elements from the Rat Elastase I Gene Function Independently of Each Other and of Heterologous Enhancers. Molec. Cell. Biol. 7, 3466–3472.

    PubMed  CAS  Google Scholar 

  26. Ornitz, D.M., Moreadith, R.W., Leder, P. (1991) Binary System for Regulating Transgene Expression in Mice: Targeting int-2 Gene Expression with Yeast GAL4/UAS Control Elements. Proc. Natl. Acad. Sci. USA 88, 698–702.

    Article  PubMed  CAS  Google Scholar 

  27. Palmiter, R.D., Behringer, R.R., Quaife, C.J., Maxwell, F., Maxwell, I.H., Brinster, R.L. (1987) Cell Lineage Ablation in Transgenic Mice by Cell-Specific Expression of a Toxin Gene. Cell 50, 435–443.

    Article  PubMed  CAS  Google Scholar 

  28. Quaife, C.J., Pinkert, C.A. Ornitz, D.M., Palmiter, R.D., Brinster, R.L. (1987) Pancreatic Neoplasia Induced by Ras Expression in Acinar Cells of Transgenic Mice. Cell 48, 1023–1034.

    Article  PubMed  CAS  Google Scholar 

  29. Seeburg, P.H., (1982) The Human Growth Hormone Gene Family: Nucleotide Sequences Show Recent Divergence and Predict a New Polypeptide Hormone. DNA 1, 239–249.

    Article  PubMed  CAS  Google Scholar 

  30. Seed, B. (1987) An LFA-3 cDNA Encodes a Phospholipid-Linked Membrane Protein Homologous to its Receptor CD2. Nature 329, 840–842.

    Article  PubMed  CAS  Google Scholar 

  31. Stewart, T.A., Pattengale, P.K., Leder, P. (1984) Spontaneous Mammary Adenocarcinomas in Transgenic Mice that Carry and Express MTV/myc Fusion Genes. Cell, 38, 627–637.

    Article  PubMed  CAS  Google Scholar 

  32. Tepper, R.I., Levinson, D.A., Stanger, B.Z., Campos-Torres, J., Abbas, A.K., Leder, P. (1990) IL4 Induces Allergic-like Inflamatory Disease and Alters T Cell Development in Transgenic Mice. Cell 62, 457–467.

    Article  PubMed  CAS  Google Scholar 

  33. Vijver van de, M., Bersselaar van de, R., Devilee, P., Cornelisse, C., Peterse, J., Nusse, R. (1987) Amplification of the Neu (c-erbB-2) Oncogene in Human Mammary Tumors is Relatively Frequent and is Often Accompanied by Amplification of the Linked c-erbA Oncogene. Molec. Cell. Biol. 7, 2019–2023.

    PubMed  Google Scholar 

  34. Webster, N., Jin, J.R., Green, S., Hollis, M., Chambon, P. (1988) The Yeast UASG is a Transcriptional Enhancer in Human HeLa Cells in the Presence of the GAL4 Trans-Activator. Cell 52, 169–178.

    Article  PubMed  CAS  Google Scholar 

  35. Wilkinson, D. G., Peters, G., Dickson, C., McMahon, A. P. (1988) Expression of the FGF-Related proto-oncogene Int-2 During Gastrulation and Neurulation in the Mouse. EMBO J. 7, 691–695.

    PubMed  CAS  Google Scholar 

  36. Zhou, D.J., Casey, G., Cline, M.J. (1988) Amplification of Human Int-2 in Breast Cancers and Squamous Carcinomas. Oncogene 2, 279–282.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Howard Hughes Medical Institute and Department of Genetics, Harvard Medical School, 25 Shattuck Street, Boston, Massachusetts, 02115, USA

    David M. Ornitz, Radek Skoda, Randall W. Moreadith & Philip Leder

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  1. David M. Ornitz
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  2. Radek Skoda
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  3. Randall W. Moreadith
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  4. Philip Leder
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Editors and Affiliations

  1. Consulting in Health and Environmental Protection, Simpsonville, Maryland, USA

    Constantine Zervos

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© 1992 Springer Science+Business Media New York

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Ornitz, D.M., Skoda, R., Moreadith, R.W., Leder, P. (1992). Regulating Gene Expression in Mammalian Cell Culture and Transgenic Mice with Yeast GAL4/UAS Control Elements. In: Zervos, C. (eds) Oncogene and Transgenics Correlates of Cancer Risk Assessments. NATO ASI Series, vol 232. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-3056-5_12

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  • DOI: https://doi.org/10.1007/978-1-4615-3056-5_12

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-6333-0

  • Online ISBN: 978-1-4615-3056-5

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