Multicellular living organisms and unmodified parts thereof and – Nonhuman animal
Patent
1997-07-30
1999-04-27
Crouch, Deborah
Multicellular living organisms and unmodified parts thereof and
Nonhuman animal
800DIG1, 4351723, 424 92, C12N 1500, C12N 500, A61K 4900
Patent
active
058980946
ABSTRACT:
A method of preparing a transgenic animal model with enhanced, accelerated pathology for Alzheimer's Disease (AD) and the transgenic animal made by the method is disclosed. The method includes producing an F.sub.1 generation by crossing a first and second transgenic parent each carrying a different expressible transgene for differing aspects of the same desired phenotype associated with AD pathology. The offspring of the F.sub.1 generation are then screened and those which carry a transgene from each parental transgenic animal resulting in an enhanced pathology for Alzheimer's Disease are selected. In a preferred embodiment the AD-associated pathology is for amyloid accumulation. In an embodiment a mutant presenilin transgene and a transgene for a mutant amyloid precursor protein are used. In a further embodiment the mutant presenilin transgene is the PS1 M146L mutation and the mutant amyloid precursor protein transgene is the Swedish mutation (APP695 isoform containing a K670N,M671L mutation (APP770 numbering)).
REFERENCES:
patent: 4736866 (1988-04-01), Leder et al.
patent: 4873191 (1989-10-01), Wagner et al.
patent: 5151508 (1992-09-01), Salbaum et al.
patent: 5175383 (1992-12-01), Leder et al.
patent: 5175384 (1992-12-01), Krimpenfort et al.
patent: 5221778 (1993-06-01), Bryre et al.
patent: 5288846 (1994-02-01), Quertermous et al.
patent: 5298422 (1994-03-01), Schwartz et al.
patent: 5347075 (1994-09-01), Sorge
patent: 5387742 (1995-02-01), Cordell
patent: 5464764 (1995-11-01), Capecchi et al.
patent: 5525714 (1996-06-01), Van Broeckhoven et al.
patent: 5602299 (1997-02-01), Lazzarini
patent: 5604131 (1997-12-01), Wadsworth et al.
patent: 5612486 (1997-03-01), McConlogue et al.
Ali et al., 1996. Artificial Strain-Specific Signs of Incipient Brain Amyloidosis in APP Transgenic Mice. Neur. of Aging, 17(2):223-234.
Andra et al., 1996, "Expression of APP in Transgenic Mice: A Comparison of Neuron-Specific Promoters", Neur. of Aging, 17(2)P183-P190.
Borchelt et al., 1996, "Familial Alzheimer's Disease-Linked Presenilin 1 Variants Elevate A-.beta.-1-42/1-40 Ratio in Vitro and in Vivo", Neuron, 17:1005-1013.
Burke and Olson, 1991. "Preparation of Clone Libraries in Yeast Artificial-Chromosome Vectors" in Meth. in Enzymology, vol. 194, Academic Press, Inc., Chap. 17, pp. 251-270.
Cai et al., 1993, "Release of Excess Amyloid .beta. Protein from a Mutant Amyloid .beta. Protein Precursor", Science, 259:514-516.
Capecchi, 1989, "Altering the genome by homologous recombination" Science, 244:1288-1292.
Citron et al., 1992, "Mutation of the .beta.-amyloid precursor protein in familial Alzheimer's disease increases .beta.-protein production", Nature 360:672.
Cruts et al., 1996, "The Presenilin Genes: A New Gene Family Involved in Alzheimer Disease Pathology", Human Molecular Genetics, 5 (Review):1449-1455.
Davies et al., 1992, "Targeted alterations in yeast artificial chromosomes for inter-species gene transfer", Nucleic Acids Research, 20(11):2693-2698.
Dickinson et al., 1993, "High frequency gene targeting using insertional vectors", Human Molecular Genet., 2(8):1299-1302.
Duff et al., 1996, "Increased amyloid-.beta.42(43) in brains of mice expressing mutant presenilin 1", Nature, 383:710-713.
Duff and Lincoln, 1995. "Insertion of pathogenic mutation into yeast artificial chromosome containing human APP gene and expression in ES cells", Res. Adv. in Alzheimer's Disease.
Games et al., 1995, "Alzheimer-type neuropathology in transgenic mice overexpressing V717F. .beta.-amyloid precursor protein", Nature, 373:523-527.
Goate et al., 1991, "Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease", Nature 349:704-706.
Gordon, 1989, "Transgenic Animals", Intl. Rev. Cytol, 115:171-229.
Hsiao et al., 1996, "Correlative Memory Deficits, A-.beta. Elevation and Amyloid Plaques in Transgenic Mice", Science, 274:99-102.
Hsiao et al., 1995, "Age-Related CNS Disorder and Early Death in Transgenic FVB/N Mice Overexpressing Alzheimer Amyloid Precursor Proteins", Neuron, 15:1203-1218.
Huxley et al., 1991, "The human HPRT gene on a yeast artificial chromosome is functional when transferred to mouse cells by cell fusion", Genomics, 9:742-750.
Jakobovits et al., 1993, "Germ-line transmission and expression of a human-derived yeast artificial chromosome", Nature, 362:255-261.
Jarrett et al., 1993, "Carboxy Terminus of .beta.-Amyloid Protein is Critical for Seeding of Amyuloid Formation . . . ", Biochemistry, 32:4693-4697.
Lalonde and Thifault, 1994, "Absence of an Association Between Motor Coordination and Spatial Orientation in Lurcher Mutant Mice", Behavior, 24:497-501.
Lamb et al., 1993. "Introduction and expression of the 400 kilobase precursor amyloid protein gene in transgenic mice", Nature Genetics, 5:22-29.
Lavitrano et al, 1989, "Sperm Cells as Vectors for Introducing Foreign DNA into Eggs: Genetic Transformation of Mice" Cell 57:717-723.
Levy-Lahad et al., 1995, "Candidate Gene for Chromosome 1 Familial Alzheimer's Disease Locus", Science, 269:973-977.
L'Hernault and Arduengo, 1992, "Mutation of Putative Sperm Membrane Protein in Caenorhabditis elegans Prevents Sperm Differentiation",.J. Cell Biology, 119(1):55-68.
Lo, 1983, "Transformation by Iontophoretic Microinjection of DNA Multiple Integrations Without Tandem Insertions", Mol. Cell. Biol 3(10):1803-1814.
Loring et al., 1996, "Rational Design of Animal Model for Alzheimer's Disease: Intro. of Mult. Human Genomic Transgenes . . . ", Neur. of Aging, 17(2):173-182.
Mann et al., 1996, "Amyloid .beta. Protein Deposition in Chrom. 14-linked Alzheimer's Disease", Annals Neurol, 40:149-156.
Malherbe et al., 1996, "Lack of .beta.-Amyloidosis in Transgenic Mice Expressing Low Levels of Aamilial Alzheimer's Disease Missence Mutations", 17(2): 205-214.
Mucke et al., 1994, "Synaptotrophic effects of human amyloid .beta. protein precursors in cortex of transgenic mice", Brain Res., 666:151-167.
Neve et al., 1996, "Transgenic Mice expressing APP-C100 in the Brain", Neuro. of Aging, 17(2):191-203.
Pearson and Choi, 1993, "Expression of the human b-amyloid precursor protein gene from a yeast artificial chromosome in transgenic mice". Proc. Natl. Scad. Sci. USA, 90:10578-10582.
Reaume et al., 1996, Enhanced amyuloidogenic processing of the .beta.-amyloid precursor protein in gene-targeted mice . . . , J. Biol. Chem. 271(38):23380-23388.
Rothstein, 1991, "Targeting, disruption, replacement, and allele rescue: integrative DNA transformation in yeast" in Meth. in Enzymology, (Academic Press) Chap. 19, 194:281-301.
Schedl et al., 1993, "A yeast artificial chromosome covering the tyrosinase gene confers copy number-dependent expression in transgenic mice", Nature, vol. 362:258-261.
Scheuner et al., 1996, "Secreted amyloid b-protein similar to that in senile plaques of AD is increased in vivo by presenilin 1 and 2 . . . ", Nature Med., 2(8):864-870.
Sherrington et al., 1996, "Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease", Nature, 375:754-760.
Strauss et al., 1993, "Germ line transmission of a yeast artificial chromosome spanning the murine a.sub.1 (I) collagen locus", Science, 259:1904-1907.
Suzuki et al., 1994, "Increased Percentage of Long Amyloid .beta. Protein Secreted by Familial Amyloid .beta. Protein Precursor (.beta.APP.sub.717) Mutants", Science, 264:1336-1340.
Thompson et al, 1989, "Germ Line Transmission and Expression of a Corrected HPRT Gene Produced by Gene Targeting in Embryonic Stem Cells", Cell 56:313-321.
Van der Putten et al, 1985, "Efficient insertion of genes into the mouse germ line via retroviral vectors", PNAS USA 82:6148-6152.
Duff, 1994, "Modeling Alzheimer's Disease in Transgenic Mice", J Florida M.A. 91(9):625-628.
Felsenstein et al (1995) Alzheimer's Parkinson's Diseases, L. Hanin et al, ed., Plenum Press, New York, pp. 401-409.
Duff Karen
Hardy John
Crouch Deborah
University of South Florida
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