Intranuclear inclusions and neuritic aggregates in transgenic mice expressing a mutant N-terminal fragment of huntingtin

Human Molecular Genetics

Volumn 8, Issue 3, 1999, Pages 397-407

  Schilling, Gabriele ^a   Becher, Mark W ^a,c   Sharp, Alan H ^a   Jinnah, Hyder A ^a   Duan, Kui ^a   Kotzuk, Joyce A ^a,c   Slunt, Hilda H ^a   Ratovitski, Tamara ^a   Cooper, Julian K ^a   Jenkins, Nancy A ^b   Copeland, Neal G ^b   Price, Donald L ^a   Ross, Christopher A ^a   Borchelt, David R ^a  

^a JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b NATIONAL CANCER INSTITUTE   (United States)

^c UNIVERSITY OF NEW MEXICO HEALTH SCIENCES CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIBODY; COMPLEMENTARY DNA; GLUTAMINE; HUNTINGTIN; MUTANT PROTEIN; REPETITIVE DNA;

AMINO TERMINAL SEQUENCE; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BEHAVIOR DISORDER; CELL NUCLEUS INCLUSION BODY; COORDINATION; DEATH; GAIT DISORDER; GENE CONSTRUCT; GENE EXPRESSION; HUNTINGTON CHOREA; HYPOKINESIA; IMMUNOBLOTTING; IMMUNOREACTIVITY; MOUSE; NEUROPATHOLOGY; NEUROTOXICITY; NONHUMAN; PATHOGENESIS; PHENOTYPE; PRIORITY JOURNAL; TRANSGENIC MOUSE; TREMOR;

ANIMALS; BASE SEQUENCE; CELL NUCLEUS; DISEASE MODELS, ANIMAL; DNA PRIMERS; HUMANS; HUNTINGTON DISEASE; INCLUSION BODIES; MICE; MICE, TRANSGENIC; NERVE TISSUE PROTEINS; NEURITES; NUCLEAR PROTEINS; PEPTIDE FRAGMENTS; PHENOTYPE;

ANIMALIA; MUS MUSCULUS;

EID: 0033054555     PISSN: 09646906     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (35)

1. Harper, P.S. (1995) New genes for old diseases: the molecular basis of myotonic dystrophy and Huntington's disease. The Lumleian Lecture. J. R. Coll. Physicians Lond., 30, 221-231.
2. Ross, C.A., Margolis, R.L., Rosenblatt, A., Ranen, N.G., Becher, M.W. and Aylward, E. (1997) Huntington disease and the related disorder, dentatorubral-pallidoluysian atrophy (DRPLA). Medicine (Baltimore), 76, 305-338.
3. Paulson, H.L. and Fischbeck, K.H. (1996) Trinucleotide repeats in neurogenetic disorders. Annu. Rev. Neurosci., 19, 79-107.
4. Beal, M.F. (1994) Neurochemistry and toxin models in Huntington's disease. Curr. Opin. Neurol., 7, 542-547.
5. Housman, D. (1995) Gain of glutamines, gain of function? Nature Genet., 10, 3-4.
6. Warren, S.T. and Nelson, D.L. (1993) Trinucleotide repeat expansions in neurological disease. Curr. Opin. Neurobiol., 3, 752-759.
7. The Huntington's Disease Collaborative Research Group (1993) A novel gene containing a trinucleotide repeat that is expanded and unstable in Huntington's disease chromosomes. Cell, 72, 971-983.
8. Rubinsztein, D.C., Leggo, J., Coles, R., Almqvist, E., Biancalana, V., Cassiman, J.J., Chotai, K., Connarty, M., Crauford, D., Curtis, A., Curtis, D., Davidson, M.J., Differ, A.M., Dode, C., Dodge, A., Frontali, M., Ranen, N.G., Stine, O.C., Sherr, M., Abbott, M.H., Franz, M.L., Graham, C.A., Harper, P.S., Hedreen, J.C. and Hayden, M.R. (1996) Phenotypic characterization of individuals with 30-40 CAG repeats in the Huntington disease (HD) gene reveals HD cases with 36 repeats and apparently normal elderly individuals with 36-39 repeats. Am. J. Hum. Genet., 59, 16-22.
9. Duyao, M., Ambrose, C., Myers, R., Novelletto, A., Persichetti F., Frontali, M., Folstein, S., Ross, C.A., Franz, M., Abbott, M. et al. (1993) Trinucleotide repeat length instability and age of onset in Huntington's disease. Nature Genet., 4, 387-392.
10. Stine, O.C., Li, S.H., Pleasant, N., Wagster, M.V., Hedreen, J.C. and Ross, C.A. (1995) Expression of the mutant allele of IT-15 (the HD gene) in striatum and cortex of Huntington's disease patients. Hum. Mol. Genet., 4, 15-18.
11. Ross, C.A. (1995) When more is less: pathogenesis of glutamine repeat neurodegenerative diseases. Neuron, 15, 493-496.
12. Harper, P.S. (1997) Trinucleotide repeat disorders. J. Inherited Metab. Dis., 20, 122-124.
13. DiFiglia, M., Sapp, E., Chase, K.O., Davies, S.W. Bates, G.P., Vonsattel, J.P. and Aronin, N. (1997) Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neuntes in brain. Science, 277, 1990-1993.
14. Paulson, H.L. Perez, M.K., Trottier, Y., Trojanowski, J.Q., Subramony, S.H., Das. S.S., Vig, P., Mandel, J.L., Fischbeck, K.H. and Pittman, R.N. (1997) Intranuclear inclusions of expanded polyglutamine protein in spinocerebellar ataxia type 3. Neuron, 19, 333-344.
15. Skinner, P.J., Koshy, B.T., Cummings, C.J., Klement, I.A., Helin, K., Servadio, A., Zoghbi, H.Y. and Orr, H.T. (1998) Ataxin-1 with an expanded glutamine tract alters nuclear matrix-associated structures. Nature, 389, 971-974.
16. Mangiarini, L., Sathasivam, K., Seller, M., Cozens, B., Harper, A., Hetherington, C., Lawton, M., Trottier, Y., Lehrach, H., Davies, S.W. and Bates, G.P. (1996) Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice. Cell, 87, 493-506.
17. Davies, S.W., Turmaine, M., Cozens, B.A., DiFiglia, M., Sharp, A.H., Ross, C.A., Scherzinger, E., Wanker, E.E., Mangiarini, L. and Bates, G.P. (1997) Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation. Cell, 90, 537-548.
18. Becher, M.W., Kotzuk, J.A., Sharp, A.H., Davies, S.W., Bates, G.P., Price, D.L. and Ross, C.A. (1998) Intranuclear neuronal inclusions in Huntington's disease and dentatorubral and pallidolluysian atrophy: correlation between the density of inclusions and IT15 CAG triplet repeat length. Neurobiol. Dis., 4, 387-397.
19. Ross, C.A. (1997) Intranuclear neuronal inclusions: a common pathogenic mechanism for glutamine-repeat neurodegenerative diseases? Neuron, 19, 1147-1150.
20. Reddy, P.H., Williams, M., Charles, V., Garrett, L., Pike-Buchanan, L., Whetsell, W.O., Miller, G. and Tagle, D.A. (1998) Behavioral abnormalities and selective neuronal loss in HD transgenic mice expressing mutated full length HD cDNA. Nature Genet., 20, 198-202.
21. Ordway, J.M., Tallaksen-Greene, S., Gutekunst, C.A., Bernstein, E.M., Cearly, J.A., Wiener H.W., Dure, L.S., Lindsey, R., Hersch, S.M., Jope, R.S., Albin, R.L. and Detloff, P.J. (1997) Ectopically expressed CAG repeat causes intranuclear inclusions and a progressive late onset neurological phenotype in the mouse. Cell, 91, 753-763.
22. Borchelt, D.R., Davis, J., Fischer, M., Lee, M.K., Slunt, H.H., Ratovitsky, T., Regard, J., Copeland, N.G., Jenkins, N.A., Sisodia, S.S. and Price, D.L. (1996) A vector for expressing foreign genes in the brains and hearts of transgenic mice. Genet. Anal., 13, 159-163.
23. Sharp, A.H., Loev, S.J., Schilling, G., Li, S.H., Li, X.J., Bao, J., Wagster, M.V., Kotzuk, J.A., Steiner, J.P., Lo, A., Snyder, S.H. and Ross, C.A. (1995). Widespread expression of Huntington's disease gene (IT15) protein product. Neuron, 14, 1065-1074.
24. Bowling, A.C. and Beal, M.F. (1995) Bioenergetic and oxidative stress in neurodegenerative diseases. Life Sci., 56, 1151-1171.
25. Coyle, J.T. and Puttfarken, P. (1993) Oxidative stress, glutamate, and neurodegenerative diseases. Science, 262, 689-695.
26. Perutz, M.F. (1995) Polar zippers: their role in human disease. Pharm. Acta Helv., 69, 213-224.
27. Scherzinger, E., Lurz, R., Turmaine, M., Mangiarini, L., Hollenbach, B., Hasenbank, R., Bates, G.P., Davies, S.W., Lehrach, H. and Wanker, E.E. (1997) Huntingtin-encoded polyglutamine expansions form amyloid-like protein aggregates in vitro and in vivo. Cell, 90, 549-558.
28. Klement, I.A., Skinner, P.J., Kaytor, M.D., Vi, H., Hersch, S.M., Clark, H.B., Zoghbi, H.T. and Orr. H.T. (1998) Ataxin-1 nuclear localization and aggregation: role in polyglutamine-induced disease in SCA 1 transgenic mice. Cell, 95, 41-53.
29. Saudou, F., Finkenbeiner, S., Devys, D. and Greenberg M.E. (1998) Huntingtin acts in the nucleus to induce apoptosis but death does not correlate with the formation of intranuclear inclusions. Cell, 91, 55-66.
30. Thinakaran, G., Borchelt, D.R., Lee, M.K., Slunt, H.H., Spitzer, L., Kim, G., Ratovitsky, T., Davenport, F., Nordsledt, C., Seeger, M., Hardy, J., Levey, A.I., Gandy, S.E., Jenkins, N.A., Copeland, N.G., Price, D.L. and Sisodia, S.S. (1996) Endoproteolysis of presenilin 1 and accumulation of processed derivatives in vivo. Neuron, 17, 181-190.
31. Trottier, Y., Lutz, Y., Stevanin, G., Imbert, G., Devys, D., Cancel, G., Saudou, F., Weber, C., David, G. et al. (1995). Polyglutamine expansion as a pathological epitope in Huntington's disease and four dominant cerebellar ataxias. Nature, 378, 403-406.
32. Borchelt, D.R., Ratovitski, T., van Lare, J. Lee, M.K. Gonzales, V., Jenkins, N.A., Copeland, N.G., Price, D.L. and Sisodia, S.S. (1997) Accelerated amyloid deposition in the brains of transgenic mice coexpressing mutant presenilin 1 and amyloid precursor proteins. Neuron, 19, 939-945.
33. Becher M.W., Kotzuk, J.A., Sharp, A.M., Davies, S.W., Bates, G.P., Price, D.L. and Ross, C.A. (1998) Intranuclear neuronal inclusions in Huntington's disease and dentatorubral and pallidoluysian atrophy: correlation between the density of inclusions and the IT15 repeat length. Neurobiol. Dis., 4, 387-397.
34. Clark, H.B., Burright, E.N., Yunis, W.S., Larson, S., Wilcox, C., Hartman, B., Matilla, A., Zoghbi, H.Y. and Orr, H.T. (1997) Purkinje cell expression of a mutant allele of SCA1 in transgenic mice leads to disparate effects on motor behaviors, followed by a progressive cerebellar dysfunclion and histological alterations. J. Neurosci., 17, 7385-7395.
35. Gardner, P.R., Nguyen, D.D. and White, C.W. (1994) Aconitase is a sensitive and critical target of oxygen poisoning in cultured mammalian cells and in rat lungs. Proc. Natl Acad. Sci. USA, 91, 12248-12252.