Abstract
The construction and analysis of bacterial plasmids that contain and phenotypically express a mammalian genetic sequence are described. Such plasmids specify a protein that has enzymatic properties, immunological reactivity and molecular size characteristic of the mouse dihydrofolate reductase, and render host cells resistant to the anti-metabolic drug trimethoprim.
Similar content being viewed by others
References
Morrow, J. F. et al. Proc. natn. Acad. Sci. U.S.A. 71, 1743–1747 (1974).
Struhl, K., Cameron, J. R. & Davis, R. W. Proc. natn. Acad. Sci. U.S.A. 73, 1471–1475 (1976).
Ratzkin, G. & Carbon, J. Proc. natn. Acad. Sci U.S.A. 74, 487–491 (1977).
Vapnek, D., Hautala, J. A., Jacobson, J. W., Giles, N. H. & Kushner, S. Proc. natn. Acad. Sci. U.S.A. 74, 3508–3512 (1977).
Itakura, K. et al. Science 198, 1056–1063 (1977).
Villa-Kamaroff, L. et al. Proc. natn. Acad. Sci. U.S.A. 75, 3727–3731 (1978).
Burchall, J. J. & Hitching, G. H. Molec. Pharmacl. 1, 126–136 (1965).
Guidelines for Research Involving Recombinant DNA Molecules, 23 June, (NIH, US Department of Health, Educztion and Welfare, 1976).
Curtiss, R. III et al. in Molecular Cloning of Recombinant DNA, (eds Scott, W. A. & Werner, R.) 99–111 (Academic, New York, 1977).
Miller, J. H. in Experiments in Molecular Genetics, 218–220 (Cold Spring Harbor Laboratories, New York, 1972).
Grunstein, M. & Hogness, D. S. Proc. natn. Acad. Sci. U.S.A. 72, 3961–3965 (1975).
Erlich, H. A., Cohen, S. N. & McDevitt, H. O. Cell 13, 681–689 (1978).
Alt, F. W., Kellems, R. E., Bertino, J. R. & Schimke, R. T. J. biol. Chem. 253, 1357–1370 (1978).
Buell, G. N., Wickens, M. P., Payvar, F. & Schimke, R. T. J. biol. Chem. 253, 2471–2482 (1978).
Smith, H., Blattner, N. & Davies, J. Nucleic Acids Res. 3, 343–353 (1976).
Kleinschmidt, A. K., Lang, D., Jacherts, D. & Zahn, R. K. Biochim. biophys. Acta 61, 856–864 (1962).
Bolivar, F. et al. Gene 2, 95–113 (1977).
Chang, A. C. Y. & Cohen, S. N. J. Bact. 134, 1141–1156 (1978).
Enea, V., Vovis, G. F. & Zinder, N. D. J. molec. Biol. 96, 495–509 (1975).
Cohen, S. N., Chang, A. C. Y. & Hsu, L. Proc. natn. Acad. Sci. U.S.A. 69, 2110–2114 (1973).
Stone, D. & Phillips, A. W. FEBS Lett. 74, 85–87 (1977).
Steitz, J. A. & Steege, D. A. J. molec. Biol. 114, 545–558 (1977).
Steege, D. A. Proc. natn. Acad. Sci. U.S.A. 74, 4163–4167 (1977).
Shine, J. & Dalgarno, L. Proc. natn. Acad. Sci. U.S.A. 71, 1342–1346 (1974).
Burchall, J. J. Ann. N. Y. Acad. Sci. 186, 143–152 (1971).
Baccanari, D., Phillips, A., Smits, S., Sinsky, D. & Burchall, J. J. Biochemistry 14, 5267–5263 (1975).
Werkheiser, W. J. biol. Chem. 236, 888–893 (1961).
Alt, F. W., Kellems, R. E. & Schimke, R. T. J. biol. Chem. 251, 3063–3074 (1976).
Erlich, H. A., Levinson, J., Cohen, S. N. & McDevitt, H. O., in preparation.
Timmis, K., Cabello, F. & Cohen, S. N. Proc. natn. Acad. Sci. U.S.A. 72, 2242–2246 (1975).
Seeburg, P. H., Shine, J., Martial, J. A., Baxter, J. D. & Goodman, H. M. Nature 270, 486–494 (1977).
Wickens, M. P., Buell, G. N. & Schimke, R. T. J. biol. Chem. 253, 2483–2495 (1978).
Chang, L. M. S. & Bollum, F. J. J. biol. Chem. 246, 909–916 (1971).
Wahl, G. M., Padgett, R. A. & Stark, G. R., in preparation.
Roychoudhury, R., Jay, E. & Wu, R. Nucleic Acids Res. 3, 101–116 (1976).
Dugaiczyk, A., Boyer, H. W. & Goodman, H. M. J. molec. Biol. 96, 171–184 (1975).
McDonell, M. W., Simon, M. N. & Studier, F. W. J. molec. Biol. 110, 119–146 (1977).
Kuperstock, Y. M. & Helinski, D. R. Biochem. biophys. Res. Commun. 54, 1451–1459 (1973).
Sharp, P. A., Sugden, B. & Sambrook, J. Biochemistry 12, 3055–3063 (1974).
Maxam, A. M. & Gilbert, W. Proc. natn. Acad. Sci. U.S.A. 74, 560–564 (1977).
Sanger, F. & Coulson, A. R. FEBS Lett. 87, 107–110 (1978).
Kaufman, R. J., Dana, S. L. & Schimke, R. T., in preparation.
Lowry, O. H., Rosebrough, N. J., Farr, A. L. & Randall, R. J. J. biol. Chem. 193, 265–275 (1951).
Oka, A. & Takanami, M. Nature 264, 193–196 (1976).
Fiers, W. et al. Nature 273, 113–120 (1978).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Chang, A., Nunberg, J., Kaufman, R. et al. Phenotypic expression in E. coli of a DNA sequence coding for mouse dihydrofolate reductase. Nature 275, 617–624 (1978). https://doi.org/10.1038/275617a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/275617a0
- Springer Nature Limited
This article is cited by
-
A genome scale overexpression screen to reveal drug activity in human cells
Genome Medicine (2014)
-
Efficient Sampling of Protein Sequence Space for Multiple Mutants
Bio/Technology (1994)
-
Satellite DNA sequences flank amplified DHFR domains in marker chromosomes of mouse fibrosarcoma cells
Genetica (1994)
-
Phylogenetic relationships among laboratory and wild-origin Mus musculus strains on the basis of genomic DNA RFLPs
Mammalian Genome (1993)
-
Mouse Chromosome 13
Mammalian Genome (1992)