Longitudinal behavioral, cross-sectional transcriptional and histopathological characterization of a knock-in mouse model of Huntington's disease with 140 CAG repeats

Experimental Neurology

Volumn 228, Issue 2, 2011, Pages 173-182

  Rising, Aaron C ^a   Xu, Jia ^a   Carlson, Aaron ^a   Napoli, Vincent V ^a   Denovan Wright, Eileen M ^b   Mandel, Ronald J ^a  

^a UNIVERSITY OF FLORIDA COLLEGE OF MEDICINE   (United States)

^b DALHOUSIE UNIVERSITY   (Canada)

Author keywords

Cortical thinning; Gait analysis; Neuronal intranuclear inclusions; Rearing behavior; Rotarod; Transcriptional analysis

Indexed keywords

HUNTINGTIN; MESSENGER RNA; POLYGLUTAMINE;

AGE; ANIMAL BEHAVIOR; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BRAIN ATROPHY; BRAIN CORTEX; CAG REPEAT; CONTROLLED STUDY; CORPUS STRIATUM; EXON; FEMALE; GAIT; GENETIC TRANSCRIPTION; HETEROZYGOTE; HISTOPATHOLOGY; HOMOZYGOTE; HUNTINGTIN GENE; HUNTINGTON CHOREA; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL;

ANIMALS; BEHAVIOR, ANIMAL; CROSS-SECTIONAL STUDIES; DISEASE MODELS, ANIMAL; FEMALE; GAIT; GENE KNOCK-IN TECHNIQUES; HETEROZYGOTE DETECTION; HOMOZYGOTE; HUMANS; HUNTINGTON DISEASE; LONGITUDINAL STUDIES; MALE; MICE; MICE, INBRED C57BL; MOTOR ACTIVITY; NERVE TISSUE PROTEINS; NUCLEAR PROTEINS; ROTAROD PERFORMANCE TEST; TRINUCLEOTIDE REPEAT EXPANSION;

EID: 79952700002     PISSN: 00144886     EISSN: 10902430     Source Type: Journal    
DOI: 10.1016/j.expneurol.2010.12.017     Document Type: Article

References (96)

1. Albin R.L., Qin Y., Young A.B., Penney J.B., Chesselet M.F. Preproenkephalin messenger RNA-containing neurons in striatum of patients with symptomatic and presymptomatic Huntington's disease: an in situ hybridization study. Ann. Neurol. 1991, 30:542-549.
2. Augood S.J., Faull R.L., Emson P.C. Dopamine D1 and D2 receptor gene expression in the striatum in Huntington's disease. Ann. Neurol. 1997, 42:215-221.
3. Becher M.W., Kotzuk J.A., Sharp A.H., Davies S.W., Bates G.P., Price D.L., Ross C.A. Intranuclear neuronal inclusions in Huntington's disease and dentatorubral and pallidoluysian atrophy: correlation between the density of inclusions and IT15 CAG triplet repeat length. Neurobiol. Dis. 1998, 4:387-397.
4. Belzung C., El Hage W., Moindrot N., Griebel G. Behavioral and neurochemical changes following predatory stress in mice. Neuropharmacology 2001, 41:400-408.
5. Bender A.T., Beavo J.A. Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use. Pharmacol. Rev. 2006, 58:488-520.
6. Bibb J.A., Yan Z., Svenningsson P., Snyder G.L., Pieribone V.A., Horiuchi A., Nairn A.C., Messer A., Greengard P. Severe deficiencies in dopamine signaling in presymptomatic Huntington's disease mice. Proc. Natl Acad. Sci. USA 2000, 97:6809-6814.
7. Bidaut-Russell M., Howlett A.C. Cannabinoid receptor-regulated cyclic AMP accumulation in the rat striatum. J. Neurochem. 1991, 57:1769-1773.
8. Carter R.J., Lione L.A., Humby T., Mangiarini L., Mahal A., Bates G.P., Dunnett S.B., Morton A.J. Characterization of progressive motor deficits in mice transgenic for the human Huntington's disease mutation. J. Neurosci. 1999, 19:3248-3257.
9. Chan E.Y., Luthi-Carter R., Strand A., Solano S.M., Hanson S.A., DeJohn M.M., Kooperberg C., Chase K.O., DiFiglia M., Young A.B., Leavitt B.R., Cha J.H., Aronin N., Hayden M.R., Olson J.M. Increased huntingtin protein length reduces the number of polyglutamine-induced gene expression changes in mouse models of Huntington's disease. Hum. Mol. Genet. 2002, 11:1939-1951.
10. Craufurd D., Thompson J.C., Snowden J.S. Behavioral changes in Huntington disease. Neuropsychiatry Neuropsychol. Behav. Neurol. 2001, 14:219-226.
11. Davies S.W., Turmaine M., Cozens B.A., DiFiglia M., Sharp A.H., Ross C.A., Scherzinger E., Wanker E.E., Mangiarini L., Bates G.P. Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation. Cell 1997, 90:537-548.
12. Denovan-Wright E.M., Robertson H.A. Cannabinoid receptor messenger RNA levels decrease in a subset of neurons of the lateral striatum, cortex and hippocampus of transgenic Huntington's disease mice. Neuroscience 2000, 98:705-713.
13. Devito L.M., Eichenbaum H. Distinct contributions of the hippocampus and medial prefrontal cortex to the "what-where-when" components of episodic-like memory in mice. Behav. Brain Res. 2010, 215:318-325.
14. DiFiglia M., Sena-Esteves M., Chase K., Sapp E., Pfister E., Sass M., Yoder J., Reeves P., Pandey R.K., Rajeev K.G., Manoharan M., Sah D.W., Zamore P.D., Aronin N. Therapeutic silencing of mutant huntingtin with siRNA attenuates striatal and cortical neuropathology and behavioral deficits. Proc. Natl Acad. Sci. USA 2007, 104:17204-17209.
15. Dorner J.L., Miller B.R., Barton S.J., Brock T.J., Rebec G.V. Sex differences in behavior and striatal ascorbate release in the 140 CAG knock-in mouse model of Huntington's disease. Behav. Brain Res. 2007, 178:90-97.
16. Dowie M.J., Bradshaw H.B., Howard M.L., Nicholson L.F., Faull R.L., Hannan A.J., Glass M. Altered CB1 receptor and endocannabinoid levels precede motor symptom onset in a transgenic mouse model of Huntington's disease. Neuroscience 2009, 163:456-465.
17. Drouet V., Perrin V., Hassig R., Dufour N., Auregan G., Alves S., Bonvento G., Brouillet E., Luthi-Carter R., Hantraye P., Deglon N. Sustained effects of nonallele-specific Huntingtin silencing. Ann. Neurol. 2009, 65:276-285.
18. Feigin A., Ghilardi M.F., Huang C., Ma Y., Carbon M., Guttman M., Paulsen J.S., Ghez C.P., Eidelberg D. Preclinical Huntington's disease: compensatory brain responses during learning. Ann. Neurol. 2006, 59:53-59.
19. Folstein S.E., Chase G.A., Wahl W.E., McDonnell A.M., Folstein M.F. Huntington disease in Maryland: clinical aspects of racial variation. Am. J. Hum. Genet. 1987, 41:168-179.
20. Fotenos A.F., Snyder A.Z., Girton L.E., Morris J.C., Buckner R.L. Normative estimates of cross-sectional and longitudinal brain volume decline in aging and AD. Neurology 2005, 64:1032-1039.
21. Fujishige K., Kotera J., Michibata H., Yuasa K., Takebayashi S., Okumura K., Omori K. Cloning and characterization of a novel human phosphodiesterase that hydrolyzes both cAMP and cGMP (PDE10A). J. Biol. Chem. 1999, 274:18438-18445.
22. Gabrieli J.D., Stebbins G.T., Singh J., Willingham D.B., Goetz C.G. Intact mirror-tracing and impaired rotary-pursuit skill learning in patients with Huntington's disease: evidence for dissociable memory systems in skill learning. Neuropsychology 1997, 11:272-281.
23. Ghilardi M.F., Silvestri G., Feigin A., Mattis P., Zgaljardic D., Moisello C., Crupi D., Marinelli L., Dirocco A., Eidelberg D. Implicit and explicit aspects of sequence learning in pre-symptomatic Huntington's disease. Parkinsonism Relat. Disord. 2008, 14:457-464.
24. Glass M., Felder C.C. Concurrent stimulation of cannabinoid CB1 and dopamine D2 receptors augments cAMP accumulation in striatal neurons: evidence for a Gs linkage to the CB1 receptor. J. Neurosci. 1997, 17:5327-5333.
25. Gomez-Anson B., Alegret M., Munoz E., Monte G.C., Alayrach E., Sanchez A., Boada M., Tolosa E. Prefrontal cortex volume reduction on MRI in preclinical Huntington's disease relates to visuomotor performance and CAG number. Parkinsonism Relat. Disord. 2009, 15:213-219.
26. Graveland G.A., Williams R.S., DiFiglia M. Evidence for degenerative and regenerative changes in neostriatal spiny neurons in Huntington's disease. Science 1985, 227:770-773.
27. Gutekunst C.A., Li S.H., Yi H., Mulroy J.S., Kuemmerle S., Jones R., Rye D., Ferrante R.J., Hersch S.M., Li X.J. Nuclear and neuropil aggregates in Huntington's disease: relationship to neuropathology. J. Neurosci. 1999, 19:2522-2534.
28. Halliday G.M., McRitchie D.A., Macdonald V., Double K.L., Trent R.J., McCusker E. Regional specificity of brain atrophy in Huntington's disease. Exp. Neurol. 1998, 154:663-672.
29. Harper P.S. Clinical consequences of isolating the gene for Huntington's disease. BMJ 1993, 307:397-398.
30. Harper S.Q., Staber P.D., He X., Eliason S.L., Martins I.H., Mao Q., Yang L., Kotin R.M., Paulson H.L., Davidson B.L. RNA interference improves motor and neuropathological abnormalities in a Huntington's disease mouse model. Proc. Natl Acad. Sci. USA 2005, 102:5820-5825.
31. Hebb A.L., Robertson H.A., Denovan-Wright E.M. Striatal phosphodiesterase mRNA and protein levels are reduced in Huntington's disease transgenic mice prior to the onset of motor symptoms. Neuroscience 2004, 123:967-981.
32. Hebb A.L., Robertson H.A., Denovan-Wright E.M. Phosphodiesterase 10A inhibition is associated with locomotor and cognitive deficits and increased anxiety in mice. Eur. Neuropsychopharmacol. 2008, 18:339-363.
33. Herkenham M., Lynn A.B., de Costa B.R., Richfield E.K. Neuronal localization of cannabinoid receptors in the basal ganglia of the rat. Brain Res. 1991, 547:267-274.
34. Hickey M.A., Kosmalska A., Enayati J., Cohen R., Zeitlin S., Levine M.S., Chesselet M.F. Extensive early motor and non-motor behavioral deficits are followed by striatal neuronal loss in knock-in Huntington's disease mice. Neuroscience 2008, 157:280-295.
35. Hobbs N.Z., Henley S.M., Ridgway G., Wild E.J., Barker R., Scahill R.I., Barnes J., Fox N.C., Tabrizi S. The progression of regional atrophy in premanifest and early Huntington's disease: a longitudinal voxel-based morphometry study. J. Neurol. Neurosurg. Psychiatry 2010, 81:756-763.
36. Hobbs N.Z., Barnes J., Frost C., Henley S.M., Wild E.J., Macdonald K., Barker R.A., Scahill R.I., Fox N.C., Tabrizi S.J. Onset and progression of pathologic atrophy in Huntington disease: a longitudinal MR imaging study. AJNR Am. J. Neuroradiol. 2010, 31:1036-1041.
37. Hodgson J.G., Agopyan N., Gutekunst C.A., Leavitt B.R., LePiane F., Singaraja R., Smith D.J., Bissada N., McCutcheon K., Nasir J., Jamot L., Li X.J., Stevens M.E., Rosemond E., Roder J.C., Phillips A.G., Rubin E.M., Hersch S.M., Hayden M.R. A YAC mouse model for Huntington's disease with full-length mutant huntingtin, cytoplasmic toxicity, and selective striatal neurodegeneration. Neuron 1999, 23:181-192.
38. Hu H., McCaw E.A., Hebb A.L., Gomez G.T., Denovan-Wright E.M. Mutant huntingtin affects the rate of transcription of striatum-specific isoforms of phosphodiesterase 10A. Eur. J. Neurosci. 2004, 20:3351-3363.
39. Josiassen R.C., Curry L.M., Mancall E.L. Development of neuropsychological deficits in Huntington's disease. Arch. Neurol. 1983, 40:791-796.
40. Kuhn A., Goldstein D.R., Hodges A., Strand A.D., Sengstag T., Kooperberg C., Becanovic K., Pouladi M.A., Sathasivam K., Cha J.H., Hannan A.J., Hayden M.R., Leavitt B.R., Dunnett S.B., Ferrante R.J., Albin R., Shelbourne P., Delorenzi M., Augood S.J., Faull R.L., Olson J.M., Bates G.P., Jones L., Luthi-Carter R. Mutant huntingtin's effects on striatal gene expression in mice recapitulate changes observed in human Huntington's disease brain and do not differ with mutant huntingtin length or wild-type huntingtin dosage. Hum. Mol. Genet. 2007, 16:1845-1861.
41. Lakics V., Karran E.H., Boess F.G. Quantitative comparison of phosphodiesterase mRNA distribution in human brain and peripheral tissues. Neuropharmacology 2010, 59:367-374.
42. Lawrence A.D., Sahakian B.J., Hodges J.R., Rosser A.E., Lange K.W., Robbins T.W. Executive and mnemonic functions in early Huntington's disease. Brain 1996, 119(Pt 5):1633-1645.
43. Lawrence A.D., Hodges J.R., Rosser A.E., Kershaw A., Ffrench-Constant C., Rubinsztein D.C., Robbins T.W., Sahakian B.J. Evidence for specific cognitive deficits in preclinical Huntington's disease. Brain 1998, 121(Pt 7):1329-1341.
44. Le Moine C., Normand E., Guitteny A.F., Fouque B., Teoule R., Bloch B. Dopamine receptor gene expression by enkephalin neurons in rat forebrain. Proc. Natl Acad. Sci. USA 1990, 87:230-234.
45. Le Moine C., Normand E., Bloch B. Phenotypical characterization of the rat striatal neurons expressing the D1 dopamine receptor gene. Proc. Natl Acad. Sci. USA 1991, 88:4205-4209.
46. Levine M.S., Klapstein G.J., Koppel A., Gruen E., Cepeda C., Vargas M.E., Jokel E.S., Carpenter E.M., Zanjani H., Hurst R.S., Efstratiadis A., Zeitlin S., Chesselet M.F. Enhanced sensitivity to N-methyl-d-aspartate receptor activation in transgenic and knockin mouse models of Huntington's disease. J. Neurosci. Res. 1999, 58:515-532.
47. Lin C.H., Tallaksen-Greene S., Chien W.M., Cearley J.A., Jackson W.S., Crouse A.B., Ren S., Li X.J., Albin R.L., Detloff P.J. Neurological abnormalities in a knock-in mouse model of Huntington's disease. Hum. Mol. Genet. 2001, 10:137-144.
48. Loughney K., Snyder P.B., Uher L., Rosman G.J., Ferguson K., Florio V.A. Isolation and characterization of PDE10A, a novel human 3', 5'-cyclic nucleotide phosphodiesterase. Gene 1999, 234:109-117.
49. Luthi-Carter R., Strand A., Peters N.L., Solano S.M., Hollingsworth Z.R., Menon A.S., Frey A.S., Spektor B.S., Penney E.B., Schilling G., Ross C.A., Borchelt D.R., Tapscott S.J., Young A.B., Cha J.H., Olson J.M. Decreased expression of striatal signaling genes in a mouse model of Huntington's disease. Hum. Mol. Genet. 2000, 9:1259-1271.
50. Luthi-Carter R., Strand A.D., Hanson S.A., Kooperberg C., Schilling G., La Spada A.R., Merry D.E., Young A.B., Ross C.A., Borchelt D.R., Olson J.M. Polyglutamine and transcription: gene expression changes shared by DRPLA and Huntington's disease mouse models reveal context-independent effects. Hum. Mol. Genet. 2002, 11:1927-1937.
51. Mangiarini L., Sathasivam K., Seller M., Cozens B., Harper A., Hetherington C., Lawton M., Trottier Y., Lehrach H., Davies S.W., Bates G.P. Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice. Cell 1996, 87:493-506.
52. Marcora E., Kennedy M.B. The Huntington's disease mutation impairs Huntingtin's role in the transport of NF-{kappa}B from the synapse to the nucleus. Hum. Mol. Genet. 2010, 19:4373-4384.
53. Marcora E., Gowan K., Lee J.E. Stimulation of NeuroD activity by huntingtin and huntingtin-associated proteins HAP1 and MLK2. Proc. Natl Acad. Sci. USA 2003, 100:9578-9583.
54. McCaw E.A., Hu H., Gomez G.T., Hebb A.L., Kelly M.E., Denovan-Wright E.M. Structure, expression and regulation of the cannabinoid receptor gene (CB1) in Huntington's disease transgenic mice. Eur. J. Biochem. 2004, 271:4909-4920.
55. Menalled L., Zanjani H., MacKenzie L., Koppel A., Carpenter E., Zeitlin S., Chesselet M.F. Decrease in striatal enkephalin mRNA in mouse models of Huntington's disease. Exp. Neurol. 2000, 162:328-342.
56. Menalled L.B., Sison J.D., Wu Y., Olivieri M., Li X.J., Li H., Zeitlin S., Chesselet M.F. Early motor dysfunction and striosomal distribution of huntingtin microaggregates in Huntington's disease knock-in mice. J. Neurosci. 2002, 22:8266-8276.
57. Menalled L.B., Sison J.D., Dragatsis I., Zeitlin S., Chesselet M.F. Time course of early motor and neuropathological anomalies in a knock-in mouse model of Huntington's disease with 140 CAG repeats. J. Comp. Neurol. 2003, 465:11-26.
58. Moratalla R., Robertson H.A., Graybiel A.M. Dynamic regulation of NGFI-A (zif268, egr1) gene expression in the striatum. J. Neurosci. 1992, 12:2609-2622.
59. Morton A.J., Lagan M.A., Skepper J.N., Dunnett S.B. Progressive formation of inclusions in the striatum and hippocampus of mice transgenic for the human Huntington's disease mutation. J. Neurocytol. 2000, 29:679-702.
60. Naarding P., Kremer H.P., Zitman F.G. Huntington's disease: a review of the literature on prevalence and treatment of neuropsychiatric phenomena. Eur. Psychiatry 2001, 16:439-445.
61. Nishi A., Snyder G.L., Greengard P. Bidirectional regulation of DARPP-32 phosphorylation by dopamine. J. Neurosci. 1997, 17:8147-8155.
62. Peinemann A., Schuller S., Pohl C., Jahn T., Weindl A., Kassubek J. Executive dysfunction in early stages of Huntington's disease is associated with striatal and insular atrophy: a neuropsychological and voxel-based morphometric study. J. Neurol. Sci. 2005, 239:11-19.
63. Pfister E.L., Kennington L., Straubhaar J., Wagh S., Liu W., DiFiglia M., Landwehrmeyer B., Vonsattel J.P., Zamore P.D., Aronin N. Five siRNAs targeting three SNPs may provide therapy for three-quarters of Huntington's disease patients. Curr. Biol. 2009, 19:774-778.
64. Phillips W., Shannon K.M., Barker R.A. The current clinical management of Huntington's disease. Mov. Disord. 2008, 23:1491-1504.
65. Reed T.M., Browning J.E., Blough R.I., Vorhees C.V., Repaske D.R. Genomic structure and chromosome location of the murine PDE1B phosphodiesterase gene. Mamm. Genome 1998, 9:571-576.
66. Reiner A., Albin R.L., Anderson K.D., D'Amato C.J., Penney J.B., Young A.B. Differential loss of striatal projection neurons in Huntington disease. Proc. Natl Acad. Sci. USA 1988, 85:5733-5737.
67. Resnick S.M., Pham D.L., Kraut M.A., Zonderman A.B., Davatzikos C. Longitudinal magnetic resonance imaging studies of older adults: a shrinking brain. J. Neurosci. 2003, 23:3295-3301.
68. Richfield E.K., Maguire-Zeiss K.A., Cox C., Gilmore J., Voorn P. Reduced expression of preproenkephalin in striatal neurons from Huntington's disease patients. Ann. Neurol. 1995, 37:335-343.
69. Robins Wahlin T.B., Lundin A., Dear K. Early cognitive deficits in Swedish gene carriers of Huntington's disease. Neuropsychology 2007, 21:31-44.
70. Rodriguez-Lebron E., Denovan-Wright E.M., Nash K., Lewin A.S., Mandel R.J. Intrastriatal rAAV-mediated delivery of anti-huntingtin shRNAs induces partial reversal of disease progression in R6/1 Huntington's disease transgenic mice. Mol. Ther. 2005, 12:618-633.
71. Rosas H.D., Hevelone N.D., Zaleta A.K., Greve D.N., Salat D.H., Fischl B. Regional cortical thinning in preclinical Huntington disease and its relationship to cognition. Neurology 2005, 65:745-747.
72. Rosas H.D., Salat D.H., Lee S.Y., Zaleta A.K., Pappu V., Fischl B., Greve D., Hevelone N., Hersch S.M. Cerebral cortex and the clinical expression of Huntington's disease: complexity and heterogeneity. Brain 2008, 131:1057-1068.
73. Ruocco H.H., Lopes-Cendes I., Li L.M., Santos-Silva M., Cendes F. Striatal and extrastriatal atrophy in Huntington's disease and its relationship with length of the CAG repeat. Braz. J. Med. Biol. Res. 2006, 39:1129-1136.
74. Scahill R.I., Frost C., Jenkins R., Whitwell J.L., Rossor M.N., Fox N.C. A longitudinal study of brain volume changes in normal aging using serial registered magnetic resonance imaging. Arch. Neurol. 2003, 60:989-994.
75. Schaffar G., Breuer P., Boteva R., Behrends C., Tzvetkov N., Strippel N., Sakahira H., Siegers K., Hayer-Hartl M., Hartl F.U. Cellular toxicity of polyglutamine expansion proteins: mechanism of transcription factor deactivation. Mol. Cell 2004, 15:95-105.
76. Schilling G., Becher M.W., Sharp A.H., Jinnah H.A., Duan K., Kotzuk J.A., Slunt H.H., Ratovitski T., Cooper J.K., Jenkins N.A., Copeland N.G., Price D.L., Ross C.A., Borchelt D.R. Intranuclear inclusions and neuritic aggregates in transgenic mice expressing a mutant N-terminal fragment of huntingtin. Hum. Mol. Genet. 1999, 8:397-407.
77. Scott L., Forssberg H., Aperia A., Diaz-Heijtz R. Locomotor effects of a D1R agonist are DARPP-32 dependent in adult but not weanling mice. Pediatr. Res. 2005, 58:779-783.
78. Slow E.J., van Raamsdonk J., Rogers D., Coleman S.H., Graham R.K., Deng Y., Oh R., Bissada N., Hossain S.M., Yang Y.Z., Li X.J., Simpson E.M., Gutekunst C.A., Leavitt B.R., Hayden M.R. Selective striatal neuronal loss in a YAC128 mouse model of Huntington disease. Hum. Mol. Genet. 2003, 12:1555-1567.
79. Steffan J.S., Kazantsev A., Spasic-Boskovic O., Greenwald M., Zhu Y.Z., Gohler H., Wanker E.E., Bates G.P., Housman D.E., Thompson L.M. The Huntington's disease protein interacts with p53 and CREB-binding protein and represses transcription. Proc. Natl Acad. Sci. USA 2000, 97:6763-6768.
80. Stoof J.C., Kebabian J.W. Opposing roles for D-1 and D-2 dopamine receptors in efflux of cyclic AMP from rat neostriatum. Nature 1981, 294:366-368.
81. Stoof J.C., Verheijden P.F. D-2 receptor stimulation inhibits cyclic AMP formation brought about by D-1 receptor stimulation in rat neostriatum but not nucleus accumbens. Eur. J. Pharmacol. 1986, 129:205-206.
82. Sugars K.L., Brown R., Cook L.J., Swartz J., Rubinsztein D.C. Decreased cAMP response element-mediated transcription: an early event in exon 1 and full-length cell models of Huntington's disease that contributes to polyglutamine pathogenesis. J. Biol. Chem. 2004, 279:4988-4999.
83. Takahashi T., Nozaki K., Tsuji S., Nishizawa M., Onodera O. Polyglutamine represses cAMP-responsive-element-mediated transcription without aggregate formation. NeuroReport 2005, 16:295-299.
84. Takano H., Gusella J.F. The predominantly HEAT-like motif structure of huntingtin and its association and coincident nuclear entry with dorsal, an NF-kB/Rel/dorsal family transcription factor. BMC Neurosci. 2002, 3:15.
85. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell 1993, 72:971-983. The Huntington's Disease Collaborative Research Group.
86. Thompson J.C., Snowden J.S., Craufurd D., Neary D. Behavior in Huntington's disease: dissociating cognition-based and mood-based changes. J. Neuropsychiatry Clin. Neurosci. 2002, 14:37-43.
87. Tsou K., Brown S., Sanudo-Pena M.C., Mackie K., Walker J.M. Immunohistochemical distribution of cannabinoid CB1 receptors in the rat central nervous system. Neuroscience 1998, 83:393-411.
88. van Dellen A., Welch J., Dixon R.M., Cordery P., York D., Styles P., Blakemore C., Hannan A.J. N-Acetylaspartate and DARPP-32 levels decrease in the corpus striatum of Huntington's disease mice. NeuroReport 2000, 11:3751-3757.
89. Vonsattel J.P., Myers R.H., Stevens T.J., Ferrante R.J., Bird E.D., Richardson E.P. Neuropathological classification of Huntington's disease. J. Neuropathol. Exp. Neurol. 1985, 44:559-577.
90. Walaas S.I., Greengard P. DARPP-32, a dopamine- and adenosine 3':5'-monophosphate-regulated phosphoprotein enriched in dopamine-innervated brain regions. I. Regional and cellular distribution in the rat brain. J. Neurosci. 1984, 4:84-98.
91. Wexler N.S., Lorimer J., Porter J., Gomez F., Moskowitz C., Shackell E., Marder K., Penchaszadeh G., Roberts S.A., Gayan J., Brocklebank D., Cherny S.S., Cardon L.R., Gray J., Dlouhy S.R., Wiktorski S., Hodes M.E., Conneally P.M., Penney J.B., Gusella J., Cha J.H., Irizarry M., Rosas D., Hersch S., Hollingsworth Z., MacDonald M., Young A.B., Andresen J.M., Housman D.E., De Young M.M., Bonilla E., Stillings T., Negrette A., Snodgrass S.R., Martinez-Jaurrieta M.D., Ramos-Arroyo M.A., Bickham J., Ramos J.S., Marshall F., Shoulson I., Rey G.J., Feigin A., Arnheim N., Acevedo-Cruz A., Acosta L., Alvir J., Fischbeck K., Thompson L.M., Young A., Dure L., O'Brien C.J., Paulsen J., Brickman A., Krch D., Peery S., Hogarth P., Higgins D.S., Landwehrmeyer B. Venezuelan kindreds reveal that genetic and environmental factors modulate Huntington's disease age of onset. Proc. Natl Acad. Sci. USA 2004, 101:3498-3503.
92. Wheeler V.C., White J.K., Gutekunst C.A., Vrbanac V., Weaver M., Li X.J., Li S.H., Yi H., Vonsattel J.P., Gusella J.F., Hersch S., Auerbach W., Joyner A.L., MacDonald M.E. Long glutamine tracts cause nuclear localization of a novel form of huntingtin in medium spiny striatal neurons in HdhQ92 and HdhQ111 knock-in mice. Hum. Mol. Genet. 2000, 9:503-513.
93. Wheeler V.C., Gutekunst C.A., Vrbanac V., Lebel L.A., Schilling G., Hersch S., Friedlander R.M., Gusella J.F., Vonsattel J.P., Borchelt D.R., MacDonald M.E. Early phenotypes that presage late-onset neurodegenerative disease allow testing of modifiers in Hdh CAG knock-in mice. Hum. Mol. Genet. 2002, 11:633-640.
94. Yu Z.X., Li S.H., Nguyen H.P., Li X.J. Huntingtin inclusions do not deplete polyglutamine-containing transcription factors in HD mice. Hum. Mol. Genet. 2002, 11:905-914.
95. Zuccato C., Ciammola A., Rigamonti D., Leavitt B.R., Goffredo D., Conti L., MacDonald M.E., Friedlander R.M., Silani V., Hayden M.R., Timmusk T., Sipione S., Cattaneo E. Loss of huntingtin-mediated BDNF gene transcription in Huntington's disease. Science 2001, 293:493-498.
96. Zuccato C., Belyaev N., Conforti P., Ooi L., Tartari M., Papadimou E., MacDonald M., Fossale E., Zeitlin S., Buckley N., Cattaneo E. Widespread disruption of repressor element-1 silencing transcription factor/neuron-restrictive silencer factor occupancy at its target genes in Huntington's disease. J. Neurosci. 2007, 27:6972-6983.