Ku deficient cells and non-human transgenic animals

Details Ku deficient cells and non-human transgenic animals Ku deficient cells and non-human transgenic animals

1996-08-08

1999-09-21

Stanton, Brian R.

Multicellular living organisms and unmodified parts thereof and

Nonhuman animal

Transgenic nonhuman animal

435325, 435354, 435440, 435455, C12N 500, C12N 1500

Patent

active

059556447

ABSTRACT:
Ku deficient cells and transgenic animals are described that comprise at least one allele of the XRCC5 gene that has been mutated by targeted disruption. Fibroblasts derived from XRCC5 mutant embryos and mice were found to prematurely age. These cells displayed decreased growth, slow entry into S phase, altered colony size distribution that favored small colonies, short life span and morphology characteristic of terminal differentiation. Mutant cells were also hypersensitive to .gamma.-radiation. The tissue culture data was at least partly reproduced in vivo because mutant mice grew slower than control littermates. The XRCC5 mutation, designated xrcc5.sup.M1, was a deletion of nucleotides 701-964 that shifted the reading frame. xrcc5.sup.M1 is expected to be null because the deleted allele produced no detectable transcript and because lymphocyte development and V(D)J recombination was severely disrupted.

REFERENCES:
patent: 4873191 (1989-10-01), Wagner et al.
patent: 5162215 (1992-11-01), Bosselman et al.
patent: 5464764 (1995-11-01), Capecchi et al.
patent: 5545808 (1996-08-01), Hew et al.
Pursel et al. Genetic Engineering of Livestock. Science, vol. 244, pp. 1281-1288, Jun. 16, 1989.
Nussenzweig et al. Requirement for Ku80 in growth and immunoglobulin V(D)J recombination. Nature, vol. 382, pp. 551-555, Aug. 8, 1996.
Houdebine, Louis-Marie. Production of pharmaceutical proteins from transgenic animals. J. of Biotech. vol. 34, pp. 269-287, 1994.
Wilmut et al., 1988, "A Revolution in Animal Breeding", New Scientist, pp. 56-59.
Fassler et al. Knockout Mice: How to make them and why. Int. Arch. Allergy Immunol., vol. 106, pp. 323-334, 1995.
Bradley et al. Modifying the mouse: Design and Desire. Bio/Technology, vol. 10, pp. 534-538, May 1992.
Jeggo et al., 1995, "Manage a trois: Double strand break repair, V(D)J recombination and DNA-PK," Bioessays 17:949-957.
Zhu et al., 1996, "Ku86 deficient mice exhibit severe combined immunodeficiency and defective processing of V(D)J recombination intermediates," Cell 86:379-389.
Adra et al., 1987, "Cloning and expression of the mouse pgk-1 gene and the nucleotide sequence of its promoter", Gene 60:65-74.
Baker et al., 1995, "Male Mice Defective in the DNA Mismatch Repair Gene PMS2 Exhibit Abnormal Chromosome Synapsis in Meiosis", Cell 82:309-319.
Bayreuther et al., 1988, "Human skin fibroblasts in vitro differentiate along a terminal cell lineage", Proc. Natl. Acad. Sci. USA 85:5112-5116.
Biedermann et al., 1991, "scid mutation in mice confers hypersensitivity to ionizing radiation and a deficiency in DNA double-strand break repair", Proc. Natl. Acad. Sci. USA 88:1394-1397.
Blunt et al., 1995, "Defective DNA-Dependent Protein Kinase Activity Is Linked to V(D)J Recombination and DNA Repair Defects Associated with the Murine scid Mutation", Cell 80:813-823.
Bogue et al., 1996, "p53 is required for both radiation-induced differentiation and rescue of V(D)J rearrangement in said mouse thymocytes" Genes Dev. 10:553-565.
Bolivar et al., 1977, "Construction and Characterization of New Cloning Vehicles: II. A Multipurpose Cloning System" Gene 2:95-113.
Bosma et al., 1983, "A severe combined immunodeficiency mutation in the mouse", Nature 301:527-530.
Boubnov et al., 1995, "Complementation of the ionizing radiation sensitivity, DNA end binding, and V(D)J recombination defects of double-strand break repair mutants by the p86 Ku autoantigen", Proc. Natl. Acad. Sci. USA 92:890-894.
Bradley, 1987, In "Teratocarcinomas and embryonic stem cells: a practical approach", E. Robertson, ed. (Oxford: IRL Press), pp. 113-151.
Broder et al., "Antiretroviral Therapy in AIDS", Ann. Int. Med. 113:604-618.
Campisi, 1996, "Replicative Senescence: An Old Lives' Tale?", Cell 84:497-500.
Carroll and Bosma, 1991, "T-lymphocyte development in scid mice is arrested shortly after the initiation of T-cell receptor .delta. gene recombination", Genes Dev. 5:1357-1366.
Ch'ng et al., 1989, "Antisense RNA complementary to 3' coding and noncoding sequences of creatine kinase is a potent inhibitor of translation in vivo", Proc. Natl. Acad. Sci. USA 86:10006-10010.
Cleaver, 1994, "It Was A Very Good Year for DNA Repair", Cell 76:1-4.
de Vries et al., 1995, "Increased susceptibility to ultraviolet-B and carcinogens of mice lacking the DNA excision repair gene XPA", Nature 377:169-173.
de Wind et al., 1995, "Inactivation of the Mouse Msh2 Gene REsults in Mismatch Repair Deficiency, Methylation Tolerance, Hyperrecombination, and Predisposition to Cancer", Cell 82:321-330.
Donehower et al., 1992, "Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours", Nature 356:215-221.
Drapkin et al., 1994, "Where Transcription Meets Repair", Cell 77:9-12.
Errami et al., 1996, "Ku86 Defines the Genetic Defect and Restores X-Ray Resistance and V(D)J Recombination to Complementation Group 5 Hamster Cell Mutants", Mol. Cell. Biol. 16: 1519-1526.
Evans et al., 1981, "Establishment in culture of pluripotential cells from mouse embryos", Nature 292:154-156.
Finnie et al., 1995, "DNA-dependent protein kinase activity is absent in xrs-6 cells: Implications for site-specific recombination and DNA double-strand break repair", Proc. Natl. Acad. Sci. USA 92:320-324.
Friedberg, et al. 1995, DNA repair and mutagenesis, pp. 147-192, ASM Press Washington, D. C.
Friedberg, 1992, "Xeroderma Pigmentosum, Cockayne's Syndrome, Helicases, and DNA Repair: What's the Relationship?", Cell 71:887-889.
Fulop and Phillips, 1990, "The scid mutation in mice causes a general defect in DNA repair", Nature 347:479-482.
Gottlieb and Jackson, 1994, "Protein kinases and DNA damage", Trends Biochem. Sci. 19:500-503.
Hartley et al., 1995, "DNA-Dependent Protein Kinase Catalytic Subunit: A Relative of Phosphatidylinositol 3-Kinase and the Ataxia Telangiectasia Gene Product", Cell 82:849-856.
Hasty et al., 1991, "Target Frequency and Integration Pattern for Insertion and Replacement Vectors in Embryonic Stem Cells", Molecular and Cellular Biology 11:4509-4517.
Hasty et al., 1991, "Introduction of a subtle mutation into the Hox-2.6 locus in embryonic stem cells", Nature 350:243-246.
Helene., C. and Toulme, J., 1990, "Specific regulation of gene expression by antisense, sense and antigene nucleic acids", Biochimica Bioshys. Acta 1049:99-125.
Hunter, 1995, "When Is a Lipid Kinase Not a Lipid Kinase? When It Is a Protein Kinase", Cell 83:1-4.
Jeggo, 1990, "Studies on mammalian mutants defective in rejoining double-strand breaks in DNA", Mutation Research 239:1-16.
Jeggo, 1985, "X-Ray sensitive mutants of Chinese hamster ovary cell line: radio-sensitivity of DNA synthesis", Mutation Research 145:171-176.
Joyner et al., 1989, "Production of a mutation in mouse En-2 gene by homologous recombination in embryonic stem cells", Nature 338:153-156.
Kastan et al., 1992, "Participation of p53 Protein in the Cellular Response to DNA Damage", Cancer Res. 51:6304-6311.
Kirchgessner et al., 1995, "DNA-Dependent Kinase (p350) as a Candidate Gene for the Murine SCID Defect", Science 267:1178-1182.
Krogstad and Champoux, 1990, "Sequence-Specific Binding of DNA by the Moloney Murine Leukemia Virus Integrase Protein", J. Virol. 64:2796-2801.
Kuhn et al., 1995, "DNA-dependent protein kinase: a potent inhibitor of transcription by RNA polymerase I", Genes Dev. 9:193-203.
Lee et al., 1995, "Isolation of mammalian cell mutants that are X-ray sensitive, impaired in DNA double-strand break repair and defective V(D)J recombination", Mutation Research 336:279-291.
Lees-Miller et al., 1995, "Absence of p350 Subunit of DNA-Activated Protein Kinase from a Radiosensitive Human Cell Line", Science 267:1183-1185.
Lehmann and Carr, 1995, "The ataxia-talangiectasia gene: a link between checkpoint controls, neurodegeneration and cancer", Trends in Genet. 11:375-377.
Li et al., 1995, The XRCC4 Gene Encodes a Novel Protein Involved in DNA Double-Strand Break Repair and V(D)J Recombination, Cell 83:1079-1089.
Loreau et al., 1990, "Blockage of AMV reverse transcriptase by antisense oligodeoxynucleotides", FEBS Letters 274:53-56.
Mansour et al., 1988

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