Multicellular living organisms and unmodified parts thereof and – Nonhuman animal
Patent
1995-06-07
1999-02-02
Chambers, Jasemine C.
Multicellular living organisms and unmodified parts thereof and
Nonhuman animal
4351723, 800DIG1, C12N 500, C12N 1500
Patent
active
058667555
ABSTRACT:
Transgenic animals carrying a transgene comprising a nucleic acid molecule encoding protein useful for regulating the expression of genes in eukaryotic cells and organisms in a highly controlled manner are disclosed. In the regulatory system of the invention, transcription of a tet operator-linked nucleotide sequence is inhibited by a transcriptional inhibitor fusion protein composed of two polypeptides, a first polypeptide which binds to tet operator sequences and a second polypeptide which directly or indirectly inhibits transcription in eukaryotic cells. In various embodiment, the first polypeptide binds to tet operator sequences either: (i) in the absence but not the presence of tetracycline (or an analogue thereof) or (ii) in the presence but not the absence of tetracycline (or an analogue thereof). In a preferred embodiment, the transgene encoding the transcriptional inhibitor fusion protein is integrated at a predetermined location within the chromosome of the transgenic animal.
REFERENCES:
patent: 4833080 (1989-05-01), Brent et al.
patent: 5221778 (1993-06-01), Byrne et al.
patent: 5545808 (1996-08-01), Hew et al.
Krimpenfort et al. Generation of transgenic dairy cattle using `in vitro` embryo production. Bio/Technology. vol. 9, pp. 844-847, Sep. 1991.
Wall, R. J. Transgenic Livestock: Progress and prospects for the future. Theriogenology. vol. 45, pp. 57-68, 1996.
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.
Wyborksi, 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.
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 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 Tjian, 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) "Indentification 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.
Altschmied, L. et al., (1988) "A threonine to alanine exchange at position 40 of Tet repressor alters the recognition of the sixth base pair of tet operator from GC to AT", The EMBO Journal, vol. 7, No. 12, pp. 4011-4017.
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) "Nucelotide 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 Terinator 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.
Baniahmad, A. et al. (1992) "A Transferable Silencing Domain Is Present In the Thyroid Hormone Receptor, In the v-erbA Oncogene Product and In the Retinoic Acid Receptor", The EMBO Journal 11(3):1015-1023.
Sauer, F. and H. Jackle (1993
Bujard Hermann
Gossen Manfred
BASF Aktiengellschaft
Chambers Jasemine C.
Clark Deborah J. R.
DeConti, Jr. Giulio A.
Kara Catherine J.
LandOfFree
Animals transgenic for a tetracycline-regulated transcriptional does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Animals transgenic for a tetracycline-regulated transcriptional , we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Animals transgenic for a tetracycline-regulated transcriptional will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1118935