Multicellular living organisms and unmodified parts thereof and – Nonhuman animal
Patent
1995-06-07
1999-06-15
Chambers, Jasemine C.
Multicellular living organisms and unmodified parts thereof and
Nonhuman animal
4351723, 435 691, 435 701, 435325, 536 234, 536 241, 424 921, C12N 500, C12N 1500, C12N 1509
Patent
active
059124113
ABSTRACT:
Transgenic mice carrying a transgene comprising a nucleic acid molecule encoding protein useful for regulating the expression of genes in eukaryotic cells in a highly controlled manner are disclosed. In the regulatory system of the invention, transcription of a tet operator-linked nucleotide sequence is stimulated by a transcriptional activator fusion protein composed of two polypeptides, a first polypeptide which binds to tet operator sequences in the presence of tetracycline operatively linked to a second polypeptide activates transcription in eukaryotic cells. In a preferred embodiment, the transgene encoding the transcriptional activator fusion protein is integrated at a predetermined location within the chromosome of the transgenic mouse.
REFERENCES:
patent: 4833080 (1989-05-01), Brent et al.
patent: 5221778 (1993-06-01), Byrne et al.
Houdebine, Journal of Biotechnology, vol. 34, pp. 269-287, 1994.
Strojek & Wagner, Genetic Engineering: Principles and Methods, vol. 10, pp. 221-246, 1988.
Wall, Theriogenology, vol. 45, pp. 57-68, 1996.
Kappel et al., Current Opinion in Biotechnology, vol. 3, pp. 548-553, 1992.
Bradley et al. Biotechnology, vol. 10, pp. 534-539, 1992.
Notarianni et al., Journal of Reproduction and Fertility, vol. 41, pp. 51-56, 1990.
Agarwal, M.L. et al., "p53 Controls Both the G.sub.2 /M and the G.sub.1 Cell Cycle Checkpoints and Mediates Reversible Growth Arrest in Human fibroblasts," Proc. Natl. Acad. Sci. USA, 92: pp. 8493-8497 (1995).
Bergman, M. et al. "Overexpressed Csk Tyrosine Kinase is Localized in Focal Adhesions, Causes Reorganization of .alpha..sub.v .beta..sub.5 Integrin, and Interferes with HeLa Cell Spreading", Molecular and Cellular Biology, 15, No. 2, pp. 711-722 (1995).
Cayrol, C. et al. "Identification of Cellular Target Genes of the Epstein-Barr Virus Transactivator Zta: Activation of Transforming Growth Factor .beta.igh3 (TGF-.beta.igh3) and TGF-.beta.1", Journal of Virology, 69, No. 7, pp. 4206-4212, (1995).
Chen, Y.Q. et al. "Tumor Suppression by p21.sup.WAF11 ", Cancer Research, 55, pp. 4536-4539, (1995).
Dhawan, J. et al. "Tetracycline-Regulated Gene Expression Following Direct Gene Transfer into Mouse Skeletal Muscle", Somatic Cell and Molecular Genetics, 21, No. 4, pp. 233-240, (1995).
Efrat, S. et al. "Conditional Transformation of a Pancreatic .beta.-Cell Line Derived From Transgenic Mice Expressing A Tetracycline-Regulated Oncogene" Proc. Natl. Acad. Sci. USA, 92, pp. 3576-3580 (1995).
Gjetting, T. et al. "Regulated Expression of the Retinoblastoma Susceptibility Gene in Mammary Carcinoma Cells Restores Cyclin D1 Expression and G.sub.1 -Phase Control", Biol. Chem. Hoppe-Seyler, 376, pp. 441-446 (1995).
Haase, S.B. et al. "Transcription Inhibits the Replication of Autonomously Replicating Plasmids in Human Cells", Molecular and Cellular Biology, 14, No. 4, pp. 2516-2524 (1994).
Hennighausen, L. et al. "Conditional Gene Expression in Secretory Tissues and Skin of Transgenic Mice Using the MMTV-LTR and the Tetracycline Responsive System", Journal of Cellular Biochemistry, 59, pp. 463-472, (1995).
Howe, J.R. et al. "The Responsiveness of a Tetracycline-Sensitive Expression System Differs in Different Cell Lines", The Journal of Biological Chemistry, 270, No. 23, pp. 14168-14174, (1995).
Miller, K. et al. "The Function of Inducible Promoter Systems in F9 Embryonal Carcinoma Cells", Experimental Cell Research, 218, pp. 144-150, (1995).
Passman, R.S. et al., "Regulated Expression of Foreign Genes In Vivo After Germline Transfer", J. Clin. Invest., 94, pp. 2421-2425 (1994).
Sopher, B.L. et al., "Cytotoxicity Mediated By Conditional Expression of a Carboxyl-Terminal Derivative of the .beta.-Amyloid Precursor Protein", Molecular Brain Research, 26, pp. 207-217, (1994).
Wu, Z. et al. "Conditional Ectopic Expression of C/EBP.beta. in NIH-3T3 Cells Induces PPAR.gamma. and Stimulates Adipogenesis", Genes & Development, 9, pp. 2350-2363, (1995).
Cowell, "Repression versus activation in the control of gene transcription," Trends in Biochemical Sciencs, 19:1, 38-42 (1994).
Deuschle et al., "Tetracycline-reversible silencing of eukaryotic promoters," Mol. Cell. Biol., 15:4, 1907-1914 (1995).
Gatz et al., "Stringent repression and homogeneous de-repression by tetracycline of a modified CaMV 35S promoter in intact transgenic tobacco plants," The Plant Journal, 2:3, 397-404 (1992).
Gossen et al., "Exploiting prokaryotic elements for the control of gene activity in higher eukaryotics," Keystone Symposium on Gene Therapy and Molecular Medicine, Steamboat Springs, Colorado, Journal of Cellular Biochemistry, Supplement 0 (21A), Abstract No. C6-220, 355 (1995).
Gossen et al., "Transcriptional activation by tetracyclines in mammalian cells," Science, 268:5218, 1766-1769 (1995).
Liang et al., "Enhanced and switchable expression systems for gene-transfer," Keystone Symposium on Gene Therapy and Molecular Medicine, Steamboat Springs, Colorado, Journal of Cellular Biochemistry, Supplement 0 (21A), Abstract No. C6-220, 379 (1995).
Hinrichs, W., et al., (1994) "Structure of the Tet Repressor-Tetracycline Complex and Regulation of Antibiotic Resistance", Science, vol. 264, pp. 418-420.
Hecht, B., et al., (1993) "Noninducible Tet Repressor Mutations Map from the Operator Motif to the C Terminus", Journal of Bacteriology, vol. 175, No. 4.
Gossen, M., et al., (1993) "Control of gene activity in higher eukaryotic cells by prokaryotic regulatory elements", TIBS, vol. 18, No. 12, pp. 471-475.
Fieck, A., et al., (1992) "Modification of the E. coli Lac Repressor for Expression in Eukaryoitic Cells: Effect of Nuclear Signal Sequence on Protein Activity and Nuclear Documentation", Nucleic Acid Research, vol. 20, pp. 1785-1791.
Seipel, K., et al., (1992) "Different activation domains stimulate transcription from remote (`enhancer`) and proximal (`promoter`) positions", The EMBO Journal, vol. 11, No. 13, pp. 4961-4968.
Epstein-Baak, R., et al., (1992) "Inducible Transformation of Cells from Transgenic Mice Expressing SV40 under Lac Operon Control", Cell Growth & Differentiation, vol. 3, pp. 127-134.
Gossen, M., and Bujard, H., (1992) "Tight control of gene expression in mammalian cells by tetracycline-responsive promoters", Proceedings of the National Academy of Science, vol. 89, pp. 5547-5551.
Bradley, A., (1991) "Modifying the mammalian genome by gene targeting", Current Opinion in Biotechnology, vol. 2, pp. 832-829.
Wyborski, D.L., and Short, J.M., (1991) "Analysis of Inducers of the E. coli Lac Repressor System in Mammalian Cells and Whole Animals", Nucleic Acid Research, vol. 19, pp. 4647-4653.
Degenkolb, J., et al., (1991) "Structural Requirements of Tetracycline-Tet Repressor Interaction: Determination of Equilibrium Binding Constants for Tetracycline Analogs with the Tet Repressor", Antimicrobial Agents and Chemotherapy, vol. 35, No. 8, pp. 1591-1595.
Baim, S.B., et al., (1991) "A chimeric mammalian transactivator based on the Iac repressor that is regulated by temperature and isopropyl .beta.-D-thiogalactopyranoside", Proceedings of the National Academy of Science, vol. 88, pp. 5072-5076.
Gatz, C., et al., (1991) "Regulation of a modified CaMV 35S promoter by the Tn 10-encoder Tet receptor in transgenic tobacco", Mol. Gen. Genet., vol. 227, No. 2, pp. 229-237.
Wissmann, A., et al., (1991) "Selection for Tn10 Tet Repressor Binding to tet Operator in Escherichia coli: Isolation of Temperature-Sensitive Mutants and Combinatorial Mutagenesis in the DNA Binding Motif", Genetics, vol. 128, pp. 225-232.
Labow, M.A., et al., (1990) "Conversion of the Iac Repressor into an Allosterically Regulated Transcriptional Activator for Mammalian Cells", Molecular and Cellular Biology, vol. 10, No. 7, pp. 3343-3356.
Deuschle, U., et al., (1989) "Regulated expression of foreign genes in mammalian cells under the control of coliphage T3 RNA polymerase and Iac repressor", Proceedings of the National Academy of Science, vol. 86, pp. 5400-5404.
Capecchi, M.R., (1989) "Altering the Genome by Homologous Recombination", Science, vol. 244, pp. 1288-1292.
Mermod, N., et al., (1989) "The Pro
Bujard Hermann
Gossen Manfred
Chambers Jasemine C.
DeConti, Jr. Giulio A.
Kara Catherine J.
Schmuck Jill D.
University of Heidelberg
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