Huntington disease models and human neuropathology: Similarities and differences

Acta Neuropathologica

Volumn 115, Issue 1, 2008, Pages 55-69

  Vonsattel, Jean Paul G ^a,b  

^a Columbia University ^*  (United States)

^b Och Spine at New York Presbyterian Hospitals   (United States)

Author keywords

Huntington disease; Knockin mouse; Mice gene carriers of the HD mutation; Transgenic mouse

Indexed keywords

HUNTINGTIN;

AUTOPSY; BRAIN; BRAIN CORTEX; BRAIN NERVE CELL; CEREBELLUM; DISEASE MODEL; DISEASE SEVERITY; GENE MUTATION; GENETIC ENGINEERING; GLOBUS PALLIDUS; HETEROZYGOTE; HUMAN; HUNTINGTON CHOREA; MUTANT; NEUROPATHOLOGY; NEUROSCIENCE; NONHUMAN; PATHOGENESIS; PHENOTYPE; PRIORITY JOURNAL; REVIEW; SUBSTANTIA NIGRA; SUBTHALAMIC NUCLEUS; THALAMUS; TRANSGENIC MOUSE; WILD TYPE;

ANIMALS; DISEASE MODELS, ANIMAL; HUMANS; HUNTINGTON DISEASE; MICE; MICE, TRANSGENIC; MUTATION; NERVE TISSUE PROTEINS; NUCLEAR PROTEINS;

EID: 36949012566     PISSN: 00016322     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00401-007-0306-6     Document Type: Review

References (114)

1. Albin RL (1995) Selective neurodegeneration in Huntington's disease. Ann Neurol 38:835-836
2. Bates GP, Gonitel R (2006) Mouse models of triplet repeat diseases. Mol Biotech 32:147-158
3. Beal MF (1995) Aging, energy, and oxidative stress in neurodegenerative diseases. Ann Neurol 38:357-366
4. Beal MF, Ferrante RJ (2004) Experimental therapeutics in transgenic mouse models of Huntington's disease. Nat Rev Neurosci 5:373-384. doi: 10.1038/nrn1386
5. Becher MW, Kotzuk JA, Sharp AH, Davies SW, Bates GP, Price DL, Ross CA (1998) Intranuclear neuronal inclusions in Huntington's disease and dentatorubropallidoluysian atrophy: Correlation between the density of inclusions and IT 15 CAG triplet repeat length. Neurobiol Dis 4:387-397
6. Borrell-Pagès M, Zala D, Humbert S, Saudou F (2006) Huntington's disease: From huntingtin function and dysfunction to therapeutic strategies. Cell Mol Life Sci 63:2642-2660
7. Braak H, Braak E (1992) Allocortical involvement in Huntington's disease. Neuropathol Appl Neurobiol 18:539-547
8. Brignull HR, Moore FE, Tang SJ, Morimoto RI (2006) Polyglutamine proteins at the pathogenic threshold display neuron-specific aggregation in a pan-neuronal Caenorhabditis elegans model. J Neurosci 2006:7597-7606. doi: 10.1523/JNEUROSCI.0990-06.2006
9. Brons IGM, Smithers LE, Trotter MWB, Rugg-Gunn P, Sun B, Chuva de Sousa Lopes SM, Howlett SK, Clarkson A, Ahrlund-Richter L, Pedersen RA, Vallier L (2007) Derivation of pluripotent epiblast stem cells from mammalian embryos. Nature. doi: 10.1038/nature05950
10. Byers RK, Gilles FH, Fung C (1973) Huntington's disease in children. Neurology 23:561-569
11. Campbell AMG, Corner B, Norman RM, Urich H (1961) The rigid form of Huntington's disease. J Neurol Neurosurg Psychiatry 24:71-77
12. Carpenter MB, Sutin J (eds) (1983) Human neuroanatomy, 8 edn. Williams & Wilkins, Baltimore/London, pp 579-586
13. Cattaneo E, Zuccato C, Tartari M (2005) Normal huntingtin function: An alternative approach to Huntington's disease. Nat Rev Neurosci 6:919-930. doi: 10.1038/nrn1806
14. Cha J-H (2000) Transcriptional dysregulation in Huntington's disease. Trends Neurosci 23:387-392
15. Curtis MA, Penney EB, Pearson AG, van Roon-Mom MC, Butterworth NJ, Dragunow M, Connor B, Faull RLM (2003) Increased cell proliferation and neurogenesis in the adult human Huntington's disease brain. Proc Natl Acad Sci USA 100:9023-9027. doi: 10.1073/pnas.1532244100
16. Curtis MA, Waldvogel HJ, Synek B, Faull RLM (2005) A histochemical and immunohistochemical analysis of the subependymal layer in the normal and Huntington's disease brain. J Chem Neutoanat 30:55-66. doi: 10.1016/ j.jchemneu.2005.05.001
17. Davies SW, Turmaine M, Cozens BA, DiFiglia M, Sharp AH, Ross CA, Scherzinger E, Wanker EE, Mangiarini L, Bates GP (1997) Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation. Cell 90:537-548
18. de la Monte SM, Vonsattel JP, Richardson EP Jr (1988) Morphometric demonstration of atrophic changes in the cerebral cortex, white matter, and neostriatum in Huntington's disease. J Neuropathol Exp Neurol 47:516-525
19. DiFiglia M, Sapp E, Chase KO, Davies SW, Bates GP, Vonsattel JP, Aronin N (1997) Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science 277:1990-1993
20. Ferrante RJ, Kowall NW, Beal MF, Martin JB, Bird ED, Richardson EP (1987) Morphologic and histochemical characteristics of a spared subset of striatal neurons in Huntington's disease. J Neuropathol Exp Neurol 46:12-27
21. Folstein SE (ed) (1989) The diagnosis of Huntington's disease. In: Huntington's disease. A disorder of families. The Johns Hopkins University Press, Baltimore, pp 125-148
22. Forno LS, Jose C (1973) Huntington's chorea: A pathological study. Adv Neurol 1:453-470
23. Gil JMAC, Mohapel P, Araújo IM, Popovic N, Li J-Y, Brundin P, Petersén A (2005) Reduced hippocampal neurogenesis in R6/2 transgenic Huntington's disease mice. Neurobiol Dis 20:744-751
24. Gómez-Tortosa E, MacDonald ME, Friend JC, Taylor SAM, Weiler LJ, Cupples LA, Srinidhi J, Gusella JF, Bird ED, Vonsattel J-P, Myers RH (2001) Quantitative neuropathological changes in presymptomatic Huntington's disease. Ann Neurol 49:29-34
25. Gourfinkel-An I, Cancel G, Duyckaerts C, Faucheux B, Hauw J-J, Trottier Y, Brice A, Agid Y, Hirsch EC (1998) Neuronal distribution of intranuclear inclusions in Huntington's disease with adult onset. Neuroreport 9:1823-1826
26. Gourfinkel-An I, Cancel G, Trottier Y, Devys D, Tora L, Lutz Y, Imbert G, Saudou F, Stevanin G, Agid Y, Brice A, Mandel J-L, Hirsch EC (1997) Differential distribution of the normal and mutated forms of huntingtin in the human brain. Ann Neurol 42:712-719
27. Graham RK, Deng Y, Slow EJ, Haigh B, Bissada N, Lu G, Pearson J, Shehadeh J, Bertram L, Murphy Z, Warby SC, Doty CN, Roy S, Wellington CL, Leavitt BR, Raymond LA, Nicholson DW, Hayden MR (2006) Cleavage at the caspase-6 site is required for neuronal dysfunction and degeneration due to mutant huntingtin. Cell 125:1179-1191. doi: 10.1016/ j.cell.2006.04.026
28. Graveland GA, Williams RS, DiFiglia M (1985) Evidence for degenerative and regenerative changes in neostriatal spiny neurons in Huntington's disease. Science 227:770-773
29. Greenamyre JT (2007) Huntington's disease - making connections. N Engl J Med Line 356:518-520
30. Group: The Huntington's Disease Collaborative Research Group; MacDonald ME, Ambrose CM, Duyao MP, Myers RH, Lin C, Srinidhi L, Barnes G, Taylor SA, James M, Groot N, MacFarlane H, Jenkins B, Anderson MA, Wexler NS, Gusella JF (1993) A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell 72:971-983
31. Gutekunst C-A, Levey AI, Heilman GJ, Whaley WL, Yi H, Nash NR, Rees HD, Madden JJ, Hersch SM (1995) Identification and localization of huntingtin in brain and human lymphoblastoid cell lines with anti-fusion protein antibodies. Proc Natl Acad Sci USA 92:8710-8714
32. Gutekunst C-A, Li S-H, Mulroy JS, Kuemmerle S, Jones R, Rye D, Ferrante RJ, Hersch SM, Li X-J (1999) Nuclear and neuropil aggregates in Huntington's disease: Relationship to neuropathology. J Neurosci 19:2522-2534
33. Hallervorden J (1957) Huntingtonsche Chorea (Chorea chronica progressiva hereditaria). In: Handbuch der speziellen pathologischen Anatomie und Histologie (XIII/1 Bandteil A). Springer, Berlin, pp 793-822
34. Halliday GM, McRitchie DA, Macdonald V, Double KL, Trent RJ, McCusker E (1998) Regional specificity of brain atrophy in Huntington's disease. Exp Neurol 154:663-672
35. Harper PS, Morris MR, Quarrell OWJ, Shaw DJ, Tyler A, Youngman S (1991) The clinical neurology of Huntington's disease. In: Huntington's disease. Major problems in neurology, vol 22. W.B. Saunders, London, pp 37-80
36. Hedreen JC, Peyser CE, Folstein SE, Ross CA (1991) Neuronal loss in layers V and VI of cerebral cortex in Huntington's disease. Neurosci Lett 133:257-261
37. Hilditch-Maguire P, Trettel F, Passani LA, Auerbach A, Persichetti F, MacDonald M (2000) Huntingtin: An iron-regulated protein essential for normal nuclear and perinuclear organelles. Hum Mol Genet 9:2789-2797
38. Hockly E, Cordery PM, Woodman B, Mahal A, van Dellen A, Blakemore C, Lewis CM, Hannan AJ, Bates GP (2002) Environmental enrichment slows disease progression in R6/2 Huntington's disease mice. Ann Neurol 51:235-242. doi: 10.1002/ana.10094
39. Hodgson JG, Agopyan N, Gutekunst C-A, Leavitt BR, LePiane F, Singaraja R, Smith DJ, Bissada N, McCutcheon K, Nasir J, Jamot L, Li X-J, Stevens ME, Rosemond E, Roder JC, Phillips AG, Rubin EM, Hersch SM, Hayden MR (1999) A YAC mouse model for Huntington's disease with full-length mutant huntingtin, cytoplasmic toxicity, and selective striatal neurodegeneration. Neuron 23:182-192
40. Huang CC, Faber PW, Persichetti F, Mittal V, Vonsattel J-P, MacDonald ME, Gusella JF (1998) Amyloid formation by mutant huntingtin: Threshold, progressivity and recruitment of normal polyglutamine proteins. Somat Cell Mol Genet 24:217-233
41. Ishiguro H, Yamada K, Sawada H, Nishii K, Ichino N, Sawada M, Kurosawa Y, Matsushita N, Kobayashi K, Goto J, Hashida H, Masuda N, Kanazawa I, Nagatsu T (2001) Age-dependent and tissue-specific CAG repeat instability occurs in mouse knock-in for a mutant Huntington's disease gene. J Neurosci Res 65:289-297
42. Jervis GA (1963) Huntington's chorea in childhood. Arch Neurol 9:244-257
43. Kegel KB, Meloni AR, Yi Y, Kim YJ, Doyle E, Cuiffo BG, Sapp E, Wang Y, Qin Z-H, Chen JD, Nevins JR, Aronin N, DiFiglia M (2002) Huntingtin is present in the nucleus, interacts with the transcriptional corepressor C-terminal binding protein, and represses transcription. J Biol Chem 277:7466-7476
44. Kennedy L, Shelbourne PF (2000) Dramatic mutation instability in HD mouse striatum: Does polyglutamine load contribute to cell-specific vulnerability in Huntington's disease? Hum Mol Genet 9:2539-2544
45. Kremer B, Goldberg P, Andrew SE, Theilmann J, Telenius H, Zeisler J, Squitieri F, Lin B, Bassett A, Almqvist E, Bird TD, Hayden MR (1994) A worldwide study of the Huntington's disease mutation. The sensitivity and specificity of measuring CAG repeats. N Engl J Med Line 330:1401-1406
46. Kuemmerle S, Gutekunst C-A, Klein AM, Li X-J, Li S-H, Beal MF, Hersch SM, Ferrante RJ (1999) Huntingtin aggregates may not predict neuronal death in Huntington's disease. Ann Neurol 46:842-849
47. Kuhn A, Goldstein DR, Hodges A, Strand AD, Sengstag T, Kooperberg C, Becanovic K, Pouladi MA, Sathasivam K, Cha J-HJ, Hannan AJ, Hayden MR, Leavitt BR, Dunnett SB, Ferrante RJ, Albin R, Shelbourne P, Delorenzi M, Augood SJ, Faull RLM, Olson JM, Bates GP, Jones L, Luthi-Carter R (2007) 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 16:1845-1861. doi: 10.1093/hmg/ddm133
48. Landwehrmeyer GB, McNeil SM, Dure LS IV, Ge P, Aizawa H, Huang Q, Ambrose CM, Duyao MP, Bird ED, Bonilla E, de Young M, Avila-Gonzales AJ, Wexler NS, DiFiglia M, Gusella JF, MacDonald ME, Penney JB, Young AB, Vonsattel JP (1995) Huntington's disease gene: Regional and cellular expression in brain of normal and affected individuals. Ann Neurol 37:218-230
49. Lange H, Thörner G, Hopf A, Schröder KF (1976) Morphometric studies of the neuropathological changes in choreatic diseases. J Neurol Sci 28:401-425
50. Lazic SE, Grote H, Armstrong JE, Blakemore C, Hannan AJ, van Dellen A, Barker RA (2004) Decreased hippocampal cell proliferation in R6/1 Huntington's mice. Neuroreport 15:811-813. doi: 10.1097/ 01.wnr.0000122486.43641.90
51. Lazic SE, Grote HE, Blakemore C, Hannan AJ, van Dellen A, PhillipsW, Barker RA (2006) Neurogenesis in the R6/1 transgenic mouse model of Huntington's disease: Effects of environmental enrichment. Eur J Neurosci 23:1829-1838. doi: 10.1111/j.1460-9568.2006.04715.x
52. Levine MS, Cepeda C, Hickey MA, Fleming SM, Chesselet M-F (2004) Genetic mouse models of Huntington's and Parkinson's disease: Illuminating but imperfect. Trends Neurosci 27:691-697
53. Levine MS, Klapstein GJ, Koppel A, Gruen E, Cepeda C, Vargas ME, Jokel ES, Carpenter EM, Zanjani H, Hurst RS, Efstratiadis A, Zeitlin S, Chesselet M-F (1999) Enhanced sensitivity to N-methyl- d -aspartate receptor activation in transgenic and knockin mouse models of Huntington's disease. J Neurosci Res 58:515-532
54. Li H, Li S-H, Johnston H, Shelbourne PF, Li S-J (2000) Amino-terminal fragments of mutant huntingtin show selective accumulation in striatal neurons and synaptic toxicity. Nat Genet 25:385-389
55. Lin C-H, Tallaksen-Greene S, Chien W-M, Cearley JA, Jackson WS, Crouse AB, Ren S, Li X-J, Albin RL, Detloff PJ (2001) Neurological abnormalities in a knock-in mouse model of Huntington's disease. Hum Mol Genet 10:137-144
56. Lin MT, Beal MF (2006) Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 443:787-795. doi: 10.1038/nature05292
57. Luthi-Carter R, Hanson SA, Strand AD, Bergstrom DA, Chun W, Peters NL, Woods AM, Chan EY, Kooperberg C, Krainc D, Young AB, Tapscott SJ, Olson JM (2002) Dysregulation of gene expression in the R6/2 model of polyglutamine disease: Parallel changes in muscle and brain. Hum Mol Genet 11:1911-1926
58. Maat-Schieman MLC, Dorsman JC, Smoor MA, Siesling S, van Duinen SG, Verschuuren JGM, den Dunnen JT, van Ommen G-JB, Roos AC (1999) Distribution of inclusions in neuronal nuclei and dystrophic neurites in Huntington disease brain. J Neuropathol Exp Neurol 58:129-137
59. Macdonald V, Halliday GM, Trent RJ, McCusker EA (1997) Significant loss of pyramidal neurons in the angular gyrus of patients with Huntington's disease. Neuropathol Appl Neurobiol 23:492-495
60. Mangiarini L, Sathasivam K, Seller M, Cozens B, Harper A, Hetherington C, Lawton M, Trottier Y, Lehrach H, Davies SW, Bates GP (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
61. Margolis RL, Roos CA (2001) Expansion explosion: New clues to the pathogenesis of repeat expansion neurodegenerative diseases. Trends Mol Med 7:479-482. doi: 10.1016/S1471-4914(01)02179-7
62. Markham CH, Knox JW (1965) Observations on Huntington's chorea in childhood. J Pediatr 67:46-57
63. McCaughey WTE (1961) The pathologic spectrum of Huntington's chorea. J Nerv Ment Dis 133:91-103
64. Menalled LB, Chesselet M-F (2002) Mouse models of Huntington's disease. Trends Pharmacol Sci 23:32-39
65. Menalled LB, Sison JD, Dragatsis I, Zeitlin S, Chesselet M-F (2003) 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 465:11-26
66. Menalled LB, Sison JD, Wu U, Olivieri M, Li X-J, Li H, Zeitlin S, Chesselet M-F (2002) Early motor dysfunction and striosomal distribution of huntingtin microaggregates in Huntington's disease knock-in mice. J Neurosci 22:8266-8276
67. Myers RH, Leavitt J, Farrer LA, Jagadeesh J, McFarlane H, Mastromauro CA, Mark RJ, Gusella JF (1989) Homozygote for Huntington disease. Am J Hum Genet 45:615-618
68. Myers RH, Vonsattel JP, Paskevich PA, Kiely DK, Stevens TJ, Cupples LA, Richardson EP Jr, Bird ED (1991) Decreased neuronal and increased oligodendroglial densities in Huntington's disease caudate nucleus. J Neuropathol Exp Neurol 50:729-742
69. Myers RH, Vonsattel JP, Stevens TJ, Cupples LA, Richardson EP, Martin JB, Bird ED (1988) Clinical and neuropathologic assessment of severity in Huntington's disease. Neurology 38:341-347
70. Nance MA, Mathias-Hagen V, Breningstall G, Wick MJ, McGlennen RC (1999) Analysis of a very large trinucleotide repeat in a patient with juvenile Huntington's disease. Neurology 52:392-394
71. Nucifora FC, Sasaki M, Peters MF, Huang H, Cooper JK, Yamada M, Takahashi H, Tsuji S, Troncoso J, Dawson VL, Dawson TM, Ross CA (2001) Interference by huntingtin and atrophin-1 with CBP-mediated transcription leading to cellular toxicity. Science 291:2423-2428
72. Obrietan K, Hoyt KR (2004) CRE-mediated transcription is increased in Huntington's disease transgenic mice. J Neurosci 24:791-796. doi: 10.1523/JNEUROSCI.3493-03-2004
73. Orr HT, Zoghbi HY (2007) Trinucleotide repeat disorders. Annu Rev Neurosci 30:575-621. doi: 10.1146/annurev.neuro.29.051605.113042
74. Paulson HL (1999) Protein fate in neurodegenerative proteinopathies: polyglutamine diseases join the (mis)fold. Hum Genet 64:339-345
75. Phillips W, Morton AJ, Barker RA (2005) Abnormalities of neurogenesis in the R6/2 mouse model of Huntington's disease are attributable to the in vivo microenvironment. J Neurosci 25:11564-11576. doi: 10.1523/ JNEUROSCI.3796-05.2005
76. Project: The US - Venezuela Collaborative Research Project, Wexler NS (2004) Venezuelan kindreds reveal that genetic and environmental factors modulate Huntington's disease age of onset. Proc Natl Acad Sci USA 101:3498-3503
77. Reddy PH, Williams M, Charles V, Garrett L, Pike-Buchanan L, Whetsell WO Jr, Miller G, Tagle DA (1998) Behavioural abnormalities and selective neuronal loss in HD transgenic mice expressing mutated full-length HD cDNA. Nat Genet 20:198-202
78. Reiner A, Albin RL, Anderson KD, D'Amato CJ, Penney JB, Young AB (1988) Differential loss of striatal projection neurons in Huntington disease. Proc Natl Acad Sci USA 85:5733-5737
79. Richardson EP Jr (1990) Huntington's disease: Some recent neuropathological studies. Neuropathol Appl Neurobiol 16:451-460
80. Richfield EK, Maguire-Zeiss KA, Cox C, Gilmore J, Voorn P (1995) Reduced expression of preproenkephalin in striatal neurons from Huntington's disease patients. Ann Neurol 37:335-343
81. Roberson ED, Scearce-Levie K, Palop JJ, Yan F, Cheng IH, Wu T, Gerstein H, Yu G-Q, Mucke L (2007) Reducing endogenous tau ameliorates amyloid β-induced deficits in an Alzheimer's disease mouse model. Science 316:750-754. doi: 10.1126/science.1141736
82. Robitaille Y, Lopes-Cendes I, Becher M, Rouleau G, Clark AW (1997) The neuropathology of CAG repeat diseases: Review and update of genetic and molecular features. Brain Pathol 7:901-926
83. Roos RAC, Pruyt JFM, de Vries J, Bots GTAM (1985) Neuronal distribution in the putamen in Huntington's disease. J Neurol Neurosurg Psychiatry 48:422-425
84. Rosenberg RN (1996) DNA-triplet repeats and neurologic disease. N Engl J Med Line 335:1222-1224
85. Rubinsztein DC (2002) Lessons from animal models of Huntington's disease. Trends Genet 18:202-209
86. Rubinsztein DC, Carmichael J (2003) Huntington's disease: Molecular basis of neurodegeneration. Expert Rev Mol Med 5:1-21. doi: 10.1017/ S1462399403006549
87. Rubinsztein DC, Leggo J, Coles R, Almqvist E, Biancalana V, Cassiman J-J, Chotai K, Connarty M, Craufurd D, Curtis A, Curtis D, Davidson MJ, Differ A-M, Dode C, Dodge A, Frontali M, Ranen NG, Stine OC, Sherr M, Abbott MH, Franz ML, Graham CA, Harper PS, Hedreen JC, Jackson A, Kaplan J-C, Losekoot M, MacMillan JC, Morrison P, Trottier Y, Novelletto A, Simpson S, Theilmann J, Whittaker JL, Folstein SE, Ross CA, Hayden MR (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
88. Sapp E, Ge P, Aizawa H, Bird E, Penney J, Young AB, Vonsattel J-P, DiFiglia M (1995) Evidence for a preferential loss of enkephalin immunoreactivity in the external globus pallidus in low grade Huntington's disease using high resolution image analysis. Neuroscience 64:397-404
89. Sapp E, Kegel KB, Aronin N, Yohyama K, Uchiyama Y, Bhide P, Vonsattel JP, DiFiglia M (1999) Microglia accumulate in the HD striatum and cortex. Soc Neurosci 25:829
90. Sapp E, Penney J, Young AB, Aronin N, Vonsattel J-P, DiFiglia M (1999) Axonal transport of N-terminal huntingtin suggests early pathology of corticostriatal projections in Huntington disease. J Neuropathol Exp Neurol 58:165-173
91. Sapp E, Schwarz C, Chase K, Bhide PG, Young AB, Penney J, Vonsattel JP, Aronin N, DiFiglia M (1997) Huntingtin localization in brains of normal and Huntington's disease patients. Ann Neurol 42:604-612
92. Sathasivam K, Hobbs C, Turmaine M, Mangiarini L, Mahal A, Bertaux F, Wanker EE, Doherty P, Davies SW, Bates GP (1999) Formation of polyglutamine inclusions in non-CNS tissue. Hum Mol Genet 8:813-822
93. Scherzinger E, Lurz R, Turmaine M, Mangiarini L, Hollenbach B, Hasenbank R, Bates GP, Davies SW, Lehrach H, Wanker EE (1997) Huntingtin-encoded polyglutamine expansions form amyloid-like protein aggregates in vitro and in vivo. Cell 90:549-558
94. Schilling G, Becher MW, Sharp AH, Jinnah HA, Duan K, Kotzuk JA, Slunt HH, Ratovitski T, Cooper JK, Jenkins NA, Copeland NG, Price DL, Ross CA, Borchelt DR (1999) Intranuclear inclusions and neuritic aggregates in transgenic mice expressing a mutant N-terminal fragment of huntingtin. Hum Mol Genet 8:397-407
95. Shelbourne PF, Killeen N, Hevner RF, Johnston HM, Tecott L, Lewandoski M, Ennis M, Ramirez L, Li Z, Iannicola C, Littman DR, Myers RM (1999) A Huntington's disease CAG expansion at the murine Hdh locus is unstable and associated with behavioural abnormalities in mice. Hum Mol Genet 8:763-774
96. Slow EJ, Graham RK, Osmand AP, Devon RS, Lu G, Deng Y, Pearson J, Vaid K, Bissada N, Wetzel R, Leavitt BR, Hayden MR (2005) Absence of behavioral abnormalities and neurodegeneration in vivo despite widespread neuronal huntingtin inclusions. Proc Natl Acad Sci USA 102:11402-11407
97. Slow EJ, van Raamsdonk J, Rogers D, Coleman SH, Graham RK, Deng Y, Oh R, Bissada N, Hossain SM, Yang Y-Z, Li X-J, Simpson EM, Gutekunst C-A, Leavitt BR, Hayden MR (2003) Selective striatal neuronal loss in a YAC128 mouse model of Huntington disease. Hum Mol Genet 12:1555-1567
98. Sotrel A, Paskevich PA, Kiely DK, Bird ED, Williams RS, Myers RH (1991) Morphometric analysis of the prefrontal cortex in Huntington's disease. Neurology 41:1117-1123
99. Squitieri F, Gellera C, Cannella M, Mariotti C, Cislaghi G, Rubinsztein DC, Almqvist EW, Turner D, Bachoud-Lévi A.-C, Simpson SA, Delatycki M, Maglione V, Hayden MR, Di Donato S (2003) Homozygosity for CAG mutation in Huntington disease is associated with a more severe clinical course. Brain 126:946-955
100. Sugars KL, Rubinsztein DC (2003) Transcriptional abnormalities in Huntington disease. Trends Genet 19:233-238. doi: 10.1016/ S0168-9525(03)00074-X
101. Telenius H, Kremer B, Goldberg YP, Theilmann J, Andrew SE, Zeisler J, Adam S, Greenberg C, Ives EJ, Clarke LA, Hayden MR (1994) Somatic and gonadal mosaicism of the Huntington disease gene CAG repeat in brain and sperm. Nat Genet 6:409-414
102. Tesar PJ, Chenoweth JG, Brook FA, Davies TJ, Evans EP, Mack DL, Gardner RL, McKay RDG (2007) New cell lines from mouse epiblast share defining features with human embryonic stem cells. Nature. doi: 10.1038/ nature05972
103. Trottier Y, Lutz Y, Stevanin G, Imbert G, Devys D, Cancel G, Saudou F, Weber C, David G, Tora L, Agid Y, Brice A, Mandel J-L (1995) Polyglutamine expansion as a pathological epitope in Huntington's disease and four dominant cerebellar ataxias. Nature 378:403-406
104. Turmaine M, Raza A, Mahal A, Mangiarini L, Bates GP, Davies SW (2000) Nonapoptotic neurodegeneration in a transgenic mouse model of Huntington's disease. Proc Natl Acad Sci USA 97:8093-8097
105. van Dellen A, Blakemore C, Deacon R, York D, Hannan AJ (2000) Delaying he onset of Huntington's in mice. Nature 404:721-722
106. von Hörsten S, Schmitt I, Nguyen HP, Holzmann C, Schmidt T, Walther T, Bader M, Pabst R, Kobbe P, Krotova J, Stiller D, Kask A, Vaarmann A, Rathke-Hartlieb S, Schulz JB, Grasshoff U, Bauer I, Menezes AM, Vieira-Saecker AMM, Paul M, Jones L, Lindenberg KS, Landwehrmeyer B, Bauer A, Li X-J, Riess O (2003) Transgenic rat model of Huntington's disease. Hum Mol Genet 12. doi: 10.1093/hmg/ddg075
107. Vonsattel J-P, Myers RH, Bird ED, Ge P, Richardson EP Jr (1992) Maladie de Huntington: Sept cas avec îlots néostriataux relativement préservés. Rev Neurol 148:107-116
108. Vonsattel J-P, Myers RH, Stevens TJ, Ferrante RJ, Bird ED, Richardson EP Jr (1985) Neuropathological classification of Huntington's disease. J Neuropathol Exp Neurol 44:559-577
109. Vonsattel J-PG, DiFiglia M (1998) Huntington disease. J Neuropathol Exp Neurol 57:369-384
110. Wexler NS, Young AB, Tanzi RE, Travers H, Starosta-Rubinstein S, Penney JB, Snodgrass SR, Shoulson I, Gomez F, Arroyo MAR, Penchaszadeh GK, Moreno H, Gibbons K, Faryniarz A, Hobbs W, Anderson MA, Bonilla E, Conneally PM, Gusella JF (1987) Homozygotes for Huntington's disease. Nature 326:194-197
111. Q111 knock-in mice. Hum Mol Genet 9:503-513
112. White JK, Auerbach W, Duyao MP, Vonsattel J-P, Gusella JF, Joyner AL, MacDonald ME (1997) Huntingtin is required for neurogenesis and is not impaired by the Huntington's disease CAG expansion. Nat Genet 17:404-410
113. Yu Z-X, Li S-H, Evans J, Pillarisetti A, Li H, Li X-J (2003) Mutant huntingtin causes context-dependent neurodegeneration in mice with Huntington's disease. J Neurosci 23:2193-2202
114. Zalneraitis EL, Landis DMD, Richardson EP Jr, Selkoe DJ (1981) A comparison of astrocytic structure in cerebral cortex and striatum in Huntington's disease. Neurology 31:151