Methods for producing tetracycline-regulated transgenic mice

Multicellular living organisms and unmodified parts thereof and – Method of making a transgenic nonhuman animal – Via microinjection of dna into an embryo – egg cell – or...

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800 22, 800 18, 435455, 435463, 435 691, 4353201, 435325, C12N 500, C12N 1500, C12N 1509, C12N 1563

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059229276

ABSTRACT:
Transgenic mice carrying two transgenes, the first coding for a transactivator fusion protein comprising a tet repressor and a polypeptide which directly or indirectly activates in eucaryotic cells, and the second comprising a gene operably linked to a minimal promoter operably linked to at least one tet operator sequence, are disclosed. Isolated DNA molecules (e.g., targeting vectors) for integrating a polynucleotide sequence encoding a transactivator of the invention at a predetermined location within a second target DNA molecule by homologous recombination are also disclosed. Transgenic mice having the DNA molecules of the invention integrated at a predetermined location in a chromosome by homologous recombination are also encompassed by the invention. Methods to regulate the expression of a tet operator linked-gene of interest by administering tetracycline or a tetracycline analogue to a mouse of the invention are also disclosed. The regulatory system of the invention allows for conditional inactivation or modulation of expression of a gene of interest in a host cell or mouse.

REFERENCES:
patent: 4833080 (1989-05-01), Brent et al.
patent: 5221778 (1993-06-01), Byrne et al.
Seamark, Reproduction, Fertility and Development, vol. 6, pp. 653-657, 1994.
Mullins et al., Journal of Clinical Investigations, vol. 98, pp. S37-S40, 1996.
Wall, Theriogenology, vol. 45, pp. 57-68, 1996.
Kappel et al., Current Opinion in Biotechnology, vol. 3, pp. 548-553, 1992.
Stojek & Wagner, Genetic Engineering: Principles and Methods, vol. 10, pp. 221-246, 1988.
Ebert et al., Molecular Endocrinology, vol. 2, pp. 277-283, 1988.
Hammer et al., Journal of Animal Sciences, vol. 63, pp. 269-278, 1986.
Acklaud-Berglund, Biotechniques, vol. 19, pp. 216-217, Aug. 1995.
Houdebine, Journal of Biotechnology, vol. 34, pp. 269-287, 1994.
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 lac 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.
Labow, M.A., et al., (1990) "Conversion of the lac 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 lac 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 Proline-Rich Transcriptional Activator of CTF/NF-I Is Distinct from the Replication and DNA Binding Domain", Cell, vol. 58, 741-753.
Mansour, S.L., et al., (1988) "Disruption of the proto-oncogene int-2 in mouse embryo-derived stem cells: a general strategy for targeting mutations to non-selectable genes", Nature, vol. 336, pp. 348-352.
Gatz, C., and Quail, P.H., (1988) "Tn10-encoded tet repressor can regulate an operator-containing plant promoter", Proceedings of the National Academy of Science, vol. 85, pp. 1394-1397.
Figge, J., et al., (1988) "Stringent Regulation of Stably Integrated Chloramphenicol Acetyl Transferase Genes by E. coli lac Repressor in Monkey Cells", Cell, vol. 52, 713-722.
Triezenberg, S.J., et al., (1988) "Functional dissection of VP16, the trans-activator of herpes simplex virus immediate early gene expression", Genes & Development, vol. 2, pp. 718-729.
Courey, A.J., and Tijan, R., (1988) "Analysis of Sp1 In Vivo Reveals Multiple Transcriptional Domains, Including a Novel Glutamine-Rich Activation Motif", Cell, vol. 55, pp. 887-898.
Tovar, K., et al., (1988) "Identification and nucleotide sequence of the class E tet regulatory elements and operator and inducer binding of the encoded purified Tet repressor", Mol. Gen. Genet., vol. 215, pp. 76-80.
Brown, M., et al., (1987) "lac Repressor Can Regulate Expression from a Hybrid SV40 Early Promoter Containing a lac Operator in Animal Cells", Cell, vol. 49, pp. 603-612.
Hu,M.C-T and Davidson, N., (1987) "The Inducible lac Operator-Repressor System Is Functional in Mammalian Cells", Cell, vol. 46, pp. 555-566.
Smithies, O., et al., (1985) "Insertion of DNA sequences into the human chromosomal .beta.-globin locus by homologous recombination", Nature, vol. 317, pp. 230-234.
Boshart, M., et al., (1985) "A Very Strong Enhancer Is Located Upstream of an Immediate Early Gene of Human Cytomegalovirus", Cell, vol. 41, No. 2, pp. 521-530.
Postle, K., et al., (1984) "Nucleotide sequence of the repressor gene of the TN10 tetracycline resistance determinant", Nucleic Acid Research, vol. 12, No. 12, pp. 4849-4863.
Unger, B., et al., (1984) "Nucleotide sequence of the gene, protein purification and characterization of the pSC101-encoded tetracycline resistance-gene-repressor", Gene, vol. 31, pp. 103-108.
Unger, B., et al., (1984) "Nucleotide sequence of the repressor gene of the RA1 tetracycline resistance determinant: structural and functional comparison with three related Tet repressor genes", Nucleic Acid Research, vol. 12, No. 20, pp. 7693-7703.
Waters, S.H. et al., (1983) "The tetracycline resistance determinants of RP1 and Tn1721: nucleotide sequence analysis", Nucleic Acid Research, vol. 11, No. 17, pp. 6089-6105.
Hillen, W., and Schollmeier, K., (1983) "Nucleotide sequence of the TN10 encoded tetracycline resistance gene", Nucleic Acid Research, vol. 11, No. 2, pp. 525-539.
Brent, R. and M. Ptashne (1984) "A Bacterial Repressor Protein or a Yeast Transcriptional Terminator Can Block Upstream Activation of A Yeast Gene" Nature 312:612-615.
Brent R. and M. Ptashne (1985) "A Eukaryotic Transcriptional Activator Bearing the DNA Specificity of a Prokaryotic Repressor" Cell 43:729-736.

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