CAG repeat lengths ≥ 335 attenuate the phenotype in the R6/2 Huntington's disease transgenic mouse

Neurobiology of Disease

Volumn 33, Issue 3, 2009, Pages 315-330

  Dragatsis, I ^a   Goldowitz, D ^a   Del Mar, N ^a   Deng, Y P ^a   Meade, C A ^a   Liu, Li ^a   Sun, Z ^a   Dietrich, P ^a   Yue, J ^a   Reiner, A ^a  

^a UNIVERSITY OF TENNESSEE HEALTH SCIENCE CENTER   (United States)

Author keywords

Aggregation; CAG repeats; Huntington's disease; Nuclear entry; Pathogenesis; R6 2 mouse; Striatum

Indexed keywords

MESSENGER RNA; MUTANT PROTEIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BRAIN REGION; CODON; CONTROLLED STUDY; DENDRITE; ELECTRON MICROSCOPY; GENE EXPRESSION; GENOTYPE; HUNTINGTON CHOREA; LIFESPAN; MOUSE; NONHUMAN; NUCLEAR PORE; PATHOGENICITY; PERIKARYON; PHENOTYPE; PRIORITY JOURNAL; TRANSGENE; TRANSGENIC MOUSE;

AGING; ANIMALS; BASE SEQUENCE; BRAIN; DISEASE MODELS, ANIMAL; DNA MUTATIONAL ANALYSIS; GENE EXPRESSION; HUNTINGTON DISEASE; LONGEVITY; MICE; MICE, TRANSGENIC; MOLECULAR SEQUENCE DATA; NERVE TISSUE PROTEINS; NEURONS; NUCLEAR PROTEINS; PEPTIDES; PHENOTYPE; RNA, MESSENGER; SURVIVAL RATE; TRINUCLEOTIDE REPEAT EXPANSION;

EID: 60849109193     PISSN: 09699961     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.nbd.2008.10.009     Document Type: Article

References (119)

1. Andersen J.M., Javiar G., Djousse L., Roberts S., Brocklebank D., Cherny S.S., The US-Venezuela-Collaborative Research Group, The HD-MAPS Collaborative Research Group, Cardon L.R., Gusella J.F., MacDonald M.F., Myers R.H., Houseman D.E., and Wexler N.S. The relationship between CAG repeat length and age of onset differs for Huntington's disease patients with juvenile onset or adult onset. Ann. Hum. Gen. 71 (2006) 295-301
2. Aronin N., Kim M., Laforet G., and DiFiglia M. Are there multiple pathways in the pathogenesis of Huntington's disease? Phil. Trans. R. Soc. Lond. B 354 (1999) 995-1003
3. Arrasate M., Mitra S., Schweitzer E.S., Segal M.R., and Finkbeiner S. Inclusion body formation reduces levels of mutant huntingtin and the risk of neuronal death. Nature 431 (2004) 805-810
4. Askanas V., Serdaroglu P., Engel W.K., and Alvarez R.B. Immunocytochemical localization of ubiquitin in inclusion body myositis allows its light-microscopic distinction from polymyositis. Neurology 42 (1992) 460-461
5. Atwal R.S., Xia J., Pinchev D., Taylor J., Epand R.M., and Truant R. Huntingtin has a membrane association signal that can modulate huntingtin aggregation, nuclear entry and toxicity. Hum. Mol. Gen. 16 (2007) 2600-2615
6. Barton S., Jacak R., Khare S.D., Ding F., and Dokholyan N.V. The length dependence of the polyQ-mediated protein aggregation. J. Biol. Chem. 282 (2007) 25487-25492
7. Benn C.L., Landles C., Li H., Strand A.D., Woodman B., Sathasivam K., Li S.H., Ghazi-Noori S., Hockly E., Faruque S.M.N.N., Cha J.H.J., Sharpe P.T., Olson J.M., Li X.J., and Bates G.P. Contribution of nuclear and extranuclear polyQ to neurological phenotypes in mouse models of Huntington's disease. Hum. Mol. Gen. 14 (2005) 3065-3078
8. Bibb J.A., Yan Z., Svenningsson P., Snyder G.L., Pieribone V.A., Horiuchi A., Nairn A.C., Messer A., and Greengard P. Severe deficiencies in dopamine signaling in presymptomatic Huntington's disease mice. Proc. Natl. Acad. Sci. U.S.A. 97 (2000) 6809-6812
9. Bhide P.G., Day M., Sapp E., Schwarz C., Sheth A., Kim J., Young A.B., Penney J., Golden J., Aronin N., and DiFiglia M. Expression of normal and mutant huntingtin in the developing brain. J. Neurosci. 16 (1996) 5523-5535
10. Bowman A.B., Yoo S.Y., Dantuma N.P., and Zoghbi H.Y. Neuronal dysfunction in a polyglutamine disease model occurs in the absence of ubiquitin-proteosome system impairment and inversely correlates with degree of nuclear inclusion formation. Hum. Mol. Gen. 14 (2005) 679-691
11. Burke M.G., Woscholski R., and Yaliraki S.N. Differential hydrophobicity drives self-assembly in Huntington's disease. Proc. Natl. Acad. Sci. U.S.A. 100 (2003) 13928-13933
12. Carter R.J., Lione L.A., Humby T., Mangiarini L., Mahal A., Bates G.P., Dunnett S.B., and Morton A.J. Characterization of progressive motor deficits in mice transgenic for the human Huntington's disease mutation. J. Neurosci. 19 (1999) 3248-3257
13. Cepeda C., Ariano M.A., Calvert C.R., Flores-Hernandez J., Chandler S.H., Leavitt B.R., Hayden M.R., and Levine M.S. NMDA receptor function in mouse models of Huntington Disease. J. Neurosci. Res. 66 (2001) 525-539
14. Cepeda C., Hurst R.S., Calvert C.R., Hernandez-Echeagaray E., Nguyen O.K., Jocoy E., Christian L.J., Ariano M.A., and Levine M.S. Transient and progressive electrophysiological alterations in the corticostriatal pathway in a mouse model of Huntington's disease. J. Neurosci. 23 (2003) 961-969
15. Cha J.H., Kosinski C.M., Kerner J.A., Alsdorf S.A., Mangiarini L., Davies S.W., Penney J.B., Bates G.P., and Young A.B. Altered brain neurotransmitter receptors in transgenic mice expressing a portion of an abnormal human Huntington's disease gene. Proc. Natl. Acad. Sci. U.S.A. 95 (1998) 6480-6485
16. Chen S., Ferrone F.A., and Wetzel R. Huntington's disease age-of-onset linked to polyglutamine aggregation nucleation. Proc. Natl. Acad. Sci. U.S.A. 99 (2002) 11884-11889
17. Choong C.S., Kemppainen J.A., Zhou Z.X., and Wilson E.M. Reduced androgen receptor gene expression with first exon CAG repeat expansion. Mol. Endocrinol. 10 (1996) 1527-1535
18. Cornett J., Cao F., Wang C.E., Ross C.A., Bates G.P., Li S.H., and Li X.J. Polyglutamine expansion of huntingtin impairs its nuclear export. Nat. Genet. 37 (2005) 198-204
19. 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. Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation. Cell 90 (1997) 537-548
20. Deng Y.P., Albin R.L., Penney J.B., Young A.B., Anderson K.D., and Reiner A. Differential loss of striatal projection systems in Huntington's disease, a quantitative immunohistochemical study. J. Chem. Neuroanat. 27 (2004) 143-164
21. DiFiglia M., Sapp E., Chase K., Schwarz C., Meloni A., Young C., Martin E., Vonsattel J.P., Carraway R., Reeves S.A., Boyce F.M., and Aronin N. Huntingtin is a cytoplasmic protein associated with vesicles in human and rat brain neurons. Neuron 14 (1995) 1075-1081
22. DiFiglia M., Sapp E., Chase K.O., Davies S.W., Bates G.P., Vonsattel J.P., and Aronin J.P. Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science 277 (1997) 1990-1993
23. Dyer R.B., and McMurray C.T. Mutant protein in Huntington disease is resistant to proteolysis in affected brain. Nature Gen. 29 (2001) 270-278
24. Eriksen J.L., Przedborski S., and Petrucelli L. Gene dosage and pathogenesis of Parkinson's disease. Trends Mol. Med. 11 (2005) 91-96
25. Faber P.W., Barnes G.T., Srinidhi J., Chen J., Gusella J.F., and MacDonald M.E. Huntingtin interacts with a family of WW domain proteins. Hum. Mol. Gen. 7 (1998) 1463-1474
26. Fain J.N., Del Mar N.A., Meade C.A., Reiner A., and Goldowitz D. Abnormalities in the functioning of adipocytes from R6/2 mice that are transgenic for the Huntington's disease mutation. Hum. Mol. Gen. 10 (2001) 145-152
27. Furtado S., Suchowersky O., Rewcastle N.B., Graham L., Klimek M.L., and Garber A. Relationship between trinucleotide repeats and neuropathological changes in Huntington's disease. Ann. Neurol. 39 (1996) 132-136
28. Gambardella A., Muglia M., Labate A., Magariello A., Gabriele A.L., Mazzei R., Pirritano D., Conforti F.L., Patitucci A., Valentino P., Zappia M., and Quattrone A. Juvenile Huntington's disease presenting as progressive myoclonic epilepsy. Neurology 57 (2001) 708-711
29. Gauthier L.R., Charrin B.C., Borrell-Pages M., Dompierre J.P., Rangone H., MacDondald M.E., Lessmann V., Humbert S., and Saudou F. Huntingtin controls neurotrophic support and survival of neurons by enhancing BDNF vesicular transport along microtubules. Cell 118 (2004) 127-138
30. Glass M., Dragunow M., and Faull R.L.M. The pattern of neurodegeneration in Huntington's disease: a comparative study of cannabinoid, dopamine, adenosine and GABAA receptor alterations in the human basal ganglia in Huntington's disease. Neuroscience 97 (2000) 505-519
31. Görlich D., and Mattaj I.W. Nucleocytoplasmic transport. Science 271 (1996) 1513-1518
32. Graveland G.A., Williams R.S., and DiFiglia M. Evidence for degenerative and regenerative changes in neostriatal spiny neurons in Huntington's disease. Science 227 (1985) 770-773
33. Guidetti P., Charles V., Chen E.Y., Reddy P.H., Kordower J.H., Whetsell Jr. W.O., Schwarcz R., and Tagle D.A. Early degenerative changes in transgenic mice expressing mutant huntingtin involve dendritic abnormalities but no impairment of mitochondrial energy production. Exper. Neurol. 169 (2001) 340-350
34. Gunawardena S., and Goldstein L.S.B. Polyglutamine disease and transport problems. Deadly traffic jams on neuronal highways. Arch. Neurol. 62 (2005) 46-51
35. Gutekunst C.A., Li S.H., Yi H., Mulroy J.S., Kuemmerle S., Jones R., Rye D., Ferrante R.J., Hersch S.M., and Li X.J. Nuclear and neuropil aggregates in Huntington's disease: relationship to neuropathology. J. Neurosci. 19 (1999) 2522-2534
36. Hackam A.S., Singaraja R., Wellington C.L., Metzler M., Zhang Z., Kalchman M., and Hayden M.R. The influence of huntingtin protein size on nuclear localization and cellular toxicity. J. Cell Biol. 141 (1998) 1097-1105
37. Hackam A.S., Wellington C.L., and Hayden M.R. The fatal attraction of polyglutamine-containing proteins. Clin. Gen. 53 (1998) 233-242
38. Hockly E., Woodman B., Mahhal A., Lewis C.M., and Bates G. Standardization and statistical approaches to therapeutic trials in the R6/2 mouse. Brain Res. Bull. 61 (2005) 469-479
39. 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., and Hayden M.R. A YAC mouse model for Huntington's disease with full-length mutant huntingtin, cytoplasmic toxicity, and selective striatal neurodegeneration. Neuron 23 (1999) 181-192
40. Huntington's Disease Collaborative Research Group. A novel gene containing a trinucleotide repeat that is expanded and unstable on the HD chromosome. Cell 72 (1993) 971-983
41. Hurlbert M.S., Zhou W., Wasmeier C., Kaddis F.G., Hutton J.C., and Freed C.R. Mice transgenic for an expanded CAG repeat in the Huntington's disease gene develop diabetes. Diabetes 48 (1999) 649-651
42. Jackson W.S., Tallaksen-Greene S.J., Albin R.L., and Detloff P.J. Nucleocytoplasmic transport signals affect the age at onset of abnormalities in knock-in mice expressing polyglutamine within an ectopic protein context. Hum. Mol. Gen. 12 (2003) 1621-1629
43. Josephs K.A., Holton J.L., Rossor M.N., Godbolt A.K., Ozawa T., Strand K., Khan N., Al-Sarraj S., and Revesz T. Frontotemporal lobar degeneration and ubiquitin immunohistochemistry. Neuropath. Appl. Neurobiol. 30 (2004) 369-373
44. Kennedy L., Evans E., Chen C.M., Craven L., Detloff P.J., Ennis M., and Shelbourne P.F. Dramatic tissue-specific mutation length increases are an early molecular event in Huntington's disease pathogenesis. Hum. Mol. Gen. 12 (2003) 3359-3367
45. Kim T.W., and Tanzi R.E. Neuronal intranuclear inclusions in polyglutamine diseases: nuclear weapons or nuclear fallout. Neuron 21 (1998) 657-659
46. Klapstein G.J., Fisher R.S., Zanjani H., Cepeda C., Jokel E.S., Chesselet M.F., and Levine M.S. Electrophysiological and morphological changes in striatal spiny neurons in R6/2 Huntington's disease transgenic mice. J. Neurophysiol. 86 (2001) 2667-2677
47. Klement I.A., Skinner P.J., Kaytor M.D., Yi H., Hersch S.M., Clark H.B., Zoghbi H.Y., and Orr H.T. Ataxin-1 nuclear localization and aggregation: role in polyglutamine-induced disease in SCA1 transgenic mice. Cell 95 (1998) 41-53
48. Kuemmerle S., Gutekunst C.A., Klein A.M., Li X.J., Li S.H., Beal M.F., Hersch S.M., and Ferrante R.J. Huntingtin aggregates may not predict neuronal death in Huntington's disease. Ann. Neurol. 46 (1999) 842-849
49. Laforet G.A., Sapp E., Chase K., McIntyre C., Boyce F.M., Campbell M., Cadigan B.A., Warzecki L., Tagle D.A., Reddy P.H., Cepeda C., Calvert C.R., Jokel E.S., Klapstein G.J., Ariano M.A., Levine M.S., DiFiglia M., and Aronin N. Changes in cortical and striatal neurons predict behavioral and electrophysiological abnormalities in a transgenic murine model of Huntington's disease. J. Neurosci. 21 (2001) 9112-9123
50. La Spada A.R., and Taylor J.P. Polyglutamines placed into cortex. Neuron 38 (2003) 681-684
51. Lei W.L., Jiao Y., Del Mar N., and Reiner A. Evidence for differential cortical input to direct pathway versus indirect pathway striatal projection neurons in rats. J. Neurosci. 24 (2004) 8289-8299
52. Li S.H., and Li X.J. Aggregation of N-terminal huntingtin is dependent on the length of its glutamine repeats. Hum. Mol. Gen. 7 (1998) 777-782
53. Li H., L. S.H., Cheng A.L., Mangiarini L., Bates G.P., and Li X.J. Ultrastructural localization and progressive formation of neuropil aggregates in Huntington's disease transgenic mice. Hum. Mol. Gen. 8 (1999) 1227-1236
54. 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., and Detloff P.J. Neurological abnormalities in a knock-in mouse model of Huntington's disease. Hum. Mol. Gen. 10 (2001) 137-144
55. Lione L.A., Carter R.J., Hunt M.J., Bates G.P., Morton A.J., and Dunnett S.B. Selective discrimination learning impairments in mice expressing the human Huntington's disease mutation. J. Neurosci. 19 (1999) 10428-10437
56. 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., and Olson J.M. Decreased expression of striatal signaling genes in a mouse model of Huntington's disease. Hum. Mol. Gen. 9 (2000) 1259-1271
57. Luthi-Carter R., Hanson S.A., Strand A.D., Bergstrom D.A., Chun W., Peters N.L., Woods A.M., Chan-Kooperberg E.Y., Krainc C.D., Young A.B., Tapscott S.J., and Olson J.M. Dysregulation of gene expression in the R6/2 model of polyglutamine disease: parallel changes in muscle and brain. Hum. Mol. Gen. 11 (2002) 1911-1926
58. 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. Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice. Cell 87 (1996) 493-506
59. Maat-Schieman M.L., Dorsman J.C., Smoor M.A., Siesling S., Van Duinen S.G., Verschuuren J.J., den Dunnen J.T., Van Ommen G.J., and Roos R.A. Distribution of inclusions in neuronal nuclei and dystrophic neurites in Huntington disease brain. J. Neuropathol. Exper. Neurol. 58 (1999) 129-137
60. Martindale D., Hackam A., Wieczorek A., Ellerby L., Wellington C., McCutcheon K., Singaraja R., Kazemi-Esfarjani P., Devon R., Kim S.U., Bredesen D.E., Tufaro F., and Hayden M.R. Length of huntingtin and its polyglutamine tract influences localization and frequency of intracellular aggregates. Nature Gen. 18 (1998) 150-154
61. Meade C.A., Deng Y.P., Fusco F., Del Mar N., Hersch S., Goldowitz D., and Reiner A. Localization of neuronal intranuclear inclusions (NIIs) in the striatum and cortex of the Bates R6/2 transgenic mouse. J. Comp. Neurol. 449 (2002) 241-269
62. Menalled L., Zanjani H., MacKenzie L., Koppel A., Carpenter E., Zeitlin S., and Chesselet M.F. Decrease in striatal enkephalin mRNA in mouse models of Huntington's disease. Exper. Neurol. 162 (2000) 328-342
63. Mastroberardino P.G., Iannicola C., Nardacci R., Bernassola F., De Laurenzi V., Melino G., Moreno S., Pavone F., Oliverio S., Fesus L., and Piacentini M. `Tissue' transglutaminase ablation reduces neuronal death and prolongs survival in a mouse model of Huntington's disease. Cell Death Differ. 9 (2002) 873-880
64. Mihm M.J., Amann D.M., Schanbacher B.L., Altschuld R.A., Bauer J.A., and Hoyt K.R. Cardiac dysfunction in the R6/2 mouse model of Huntington's disease. Neurobiol. Dis. 25 (2007) 297-308
65. Milunsky J., Maher T., Loose B., Darras B., and Ito M. XL PCR for the detection of large trinucleotide expansions in juvenile Huntington's disease. Clin. Gen. 64 (2003) 70-73
66. Morton A.J., Lagan M.A., Skepper J.N., and Dunnett S.B. Progressive formation of inclusions in the striatum and hippocampus of mice transgenic for the human Huntington's disease mutation. J. Neurocytol. 29 (2000) 679-702
67. Morton, A.J., Glynn, D., Leavens, W., Zheng, Z., Skepper, J., Wigth, J., Fyfe, I., 2008. Paradoxical delay in the onset of disease caused by superlong CAG repeat expansions unmasks neurodegeneration in R6/2 mice. Hereditary Disease Foundation Symposium: HD2008: "The Milton Wexler Celebration of Life". Abst# 26.
68. Mullen R.J., Buck C.R., and Smith A.M. NeuN, a neuronal specific nuclear protein in vertebrates. Development 116 (1992) 201-211
69. Nahhas F.A., Garbern J., Krajewski K.M., Roa B.B., and Feldman G.L. Juvenile onset Huntington disease resulting from a very large maternal expansion. Am. J. Med. Gen. 137A (2005) 328-331
70. Nance M.A., Mathias-Hagen V., Breningstall G., Wick M.J., and McGlennen R.C. Analysis of a very large trinucleotide repeat in a patient with juvenile Huntington's disease. Neurology 52 (1999) 392-394
71. Narain Y., Wyttenbach A., Rankin J., Furlong R.A., and Rubinsztein D.C. A molecular investigation of true dominance in Huntington's disease. J. Med. Gen. 36 (1999) 739-746
72. Orth M., Cooper J.M., Bates G.P., and Schapira A.H. Inclusion formation in Huntington's disease R6/2 mouse muscle cultures. J. Neurochem. 87 (2003) 1-6
73. Papapetropoulos S., Lopez-Alberola R., Baumbach L., Russell A., Gonzalez M.A., Bowen B.C., and Singer C. Case of maternally transmitted juvenile Huntington's disease with a very large trinucleotide repeat. Movement Dis. 20 (2005) 1380-1383
74. Paviour D.C., Lees A.J., Josephs K.A., Ozawa T., Ganguly M., Strand C., Godbolt A., Howard R.S., Revesz T., and Holton J.L. Frontotemporal lobar degeneration with ubiquitin-only-immunoreactive neuronal changes: broadening the clinical picture to include progressive supranuclear palsy. Brain 127 (2004) 2441-2451
75. Penney Jr. J.B., Vonsattel J.P., MacDonald M.E., Gusella J.F., and Myers R.H. CAG repeat number governs the development rate of pathology in Huntington's disease. Ann. Neurol. 41 (1997) 689-692
76. Qin Z.H., Wang Y., Sapp E., Cuiffo B., Wanker E., Hayden M.R., Kegel K.B., Aronin N., and DiFiglia M. Huntingtin bodies sequester vesicle-associated proteins by a polyproline-dependent interaction. J. Neurosci. 24 (2004) 269-281
77. Reiner A., Dragatsis I., Zeitlin S., and Goldowitz D. Wild-type huntingtin plays a role in brain development and neuronal survival. Mol. Neurobiol. 28 (2003) 259-275
78. Reiner A., Del Mar N., Deng Y.P., Meade C.A., Sun Z., and Goldowitz D. R6/2 Neurons with intranuclear inclusions survive for prolonged periods in the brains of chimeric mice. J. Comp. Neurol. 505 (2007) 603-737
79. Ribchester R.R., Thomson D., Wood N.I., Hinks T., Gillingwater T.H., Wishart T.M., Court F.A., and Morton A.J. Progressive abnormalities in skeletal muscle and neuromuscular junctions of transgenic mice expressing the Huntington's disease mutation. Eur. J. Neurosci. 20 (2004) 3092-3114
80. Rigamonti D., Bauer J.H., De-Fraja C., Conti L., Sipione S., Sciorati C., Clementi E., Hackam A., Hayden M.R., Li Y., Cooper J.K., Ross C.A., Govoni S., Vincenz C., and Cattaneo E. Wild-type huntingtin protects from apoptosis upstream of caspase-3. J. Neurosci. 20 (2000) 3705-3713
81. Rosenblatt A., Liang K.Y., Zhou H., Abbott M.H., Gourley L.M., Margolis R.L., Brandt J., and Ross C.A. The association of CAG repeat length with clinical progression in Huntington's disease. Neurology 66 (2006) 1016-1020
82. Ross C.A., and Poirier M.A. Protein aggregation and neurodegenerative disease. Nature Med. 10 (2004) S10-S17
83. Sathasivam K., Woodman B., Mahal A., Bertaux F., Wanker E.E., Shima D.T., and Bates G.P. Centrosome disorganization in fibroblast cultures derived from R6/2 Huntington's disease (HD) transgenic mice and HD patients. Hum. Mol. Gen. 10 (2001) 2425-2435
84. Sanchez I., Mahlke C., and Yuan J. Pivotal role of oligomerization in expanded polyglutamine neurodegenerative disorders. Science 421 (2003) 373-379
85. Sapp E., Penney J., Young A., Aronin N., Vonsattel J.P., and DiFiglia M. Axonal transport of N-terminal huntingtin suggests early pathology of corticostriatal projections in Huntington disease. J. Neuropathol. Exper. Neurol. 58 (1999) 165-173
86. Saudou F., Finkbeiner S., Devys D., and Greenberg M.E. Huntingtin acts in the nucleus to induce apoptosis but death does not correlate with the formation of intranuclear inclusions. Cell 95 (1998) 55-66
87. 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., and Borchelt D.R. Intranuclear inclusions and neuritic aggregates in transgenic mice expressing a mutant N-terminal fragment of huntingtin. Hum. Mol. Gen. 8 (1999) 397-407
88. Schilling G., Savonenko A.V., Klevytska A., Morton J.L., Tucker S.M., Poirier M., Gale A., Chan N., Gonzales V., Slunt H.H., Coonfield M.L., Jenkins N.A., Copeland N.G., Ross C.A., and Borchelt D.R. Nuclear-targeting of mutant huntingtin fragments produces Huntington's disease-like phenotypes in transgenic mice. Hum. Mol. Gen. 13 (2004) 1599-1610
89. Seneca S., Fagnart D., Keymolen K., Lissens W., Hasaerts D., Debulpaep S., Desprechins B., Liebaers I., and De Meirleir L. Early onset Huntington disease: a neuronal degeneration syndrome. Eur. J. Pediat. 163 (2004) 71-721
90. Shelbourne P.F., Killeen N., Hevner R.F., Johnston H.M., Tecott L., Lewandoski M., Ennis M., Ramirez L., Li Z., Iannicola C., Littman D.R., and Myers R.M. A Huntington's disease CAG expansion at the murine Hdh locus is unstable and associated with behavioural abnormalities in mice. Hum. Mol. Gen. 8 (1999) 763-774
91. Shelbourne P.F., Keller-McGandy P.F., Bi W.L., Yoon S.R., Dubeau L., Veitch N.J., Vonsattel J.P., Wexler N.S., The US-Venezuela Collaborative Research Group, Arnheim N., and Augood S.J. Triplet repeat mutation length gains correlate with cell-type specific vulnerability in Huntington disease brain. Hum. Mol. Gen. 16 (2007) 133-1142
92. Sieradzan K.A., Mechan A.O., Jones L., Wanker E.E., Nukina N., and Mann D.M. Huntington's disease intranuclear inclusions contain truncated, ubiquitinated huntingtin protein. Exper. Neurol. 156 (1999) 92-99
93. Sipione S., Rigamonti D., Valenza M., Zuccato C., Conti L., Pritchard J., Kooperberg C., Olson J.M., and Cattaneo E. Early transcriptional profiles in huntingtin-inducible striatal cells by microarray analyses. Hum. Mol. Gen. 11 (2002) 1953-1965
94. Sisodia S.S. Nuclear inclusion in glutamine repeat disorders: are they pernicious, coincidental or beneficial?. Cell 95 (1998) 1-4
95. Slow E.J., Graham R.K., Osmand A.P., Devon R.S., Lu G., Deng Y., Pearson J., Vaid K., Bissada N., Wetzel R., Leavitt B.R., and Hayden M.R. Absence of behavioral abnormalities and neurodegeneration in vivo despite widespread neuronal huntingtin inclusions. Proc. Natl. Acad. Sci. U.S.A. 102 (2005) 11402-11407
96. Spillantini M.G., Crowther R.A., Jakes R., Hasegawa M., and Goedert M. Alpha-synuclein in filamentous inclusions of Lewy bodies from Parkinson's disease and dementia with Lewy bodies. Proc. Natl. Acad. Sci. U.S.A. 95 (1998) 6469-6473
97. Spires T.L., Grote H.E., Garry S., Cordery P.M., Van Dellen A., Blakemore C., and Hannan A.J. Dendritic spine pathology and deficits in experience-dependent dendritic plasticity in R6/1 Huntington's disease transgenic mice. Eur. J. Neurosci. 19 (2004) 2799-2807
98. Squitieri F., Sabbadini G., Mandich P., Gellera C., Di Maria E., Bellone E., Castellotti B., Nargi E., de Grazia U., Frontali M., and Novellotto A. Family and molecular data for a fine analysis of age at onset in Huntington Disease. Am. J. Med. Gen. 95 (2000) 366-373
99. Squitieri F., Frati L., Ciarmiello A., Lastoria S., and Quarrell O. Juvenile Huntington's disease: does a dosage-effect pathogenic mechanism differ from the classical adult disease? Mech. Aging Devel. 127 (2006) 208-212
100. Stack E.C., Kubilus J.K., Smith K., Cormier K., Del Signore S.J., Guelin E., Ryu H., Hersch S.M., and Ferrante R.J. Chronology of behavioral symptoms and neuropathological sequela in R6/2 Huntington 's disease transgenic mice. J. Comp. Neurol. 490 (2005) 354-370
101. Stine O.C., Pleasant N., Franz M.L., Abbott M.H., Folstein S.E., and Ross C.A. Correlation between the onset age of Huntington's disease and length of the trinucleotide repeat in IT15. Hum. Mol. Gen. 2 (1993) 1547-1549
102. Sun Z., Del Mar N., Meade C., Goldowitz D., and Reiner A. Differential changes in striatal projection neurons in R6/2 mice transgenic for Huntington's disease. Neurobiol. Dis. 11 (2002) 369-385
103. Suntharalingam M., and Wente S.R. Peering through the pore: nuclear pore complex structure, assembly, and function. Dev. Cell. 4 (2003) 775-789
104. Takahashi T., Kikuchi S., Katada S., Nagai Y., Nishizawa M., and Onodera O. Soluble polyglutamine oligomers formed prior to inclusion body formation are cytotoxic. Hum. Mol. Gen. 17 (2008) 345-356
105. Tekkok S.B., and Goldberg M.P. AMPA/kainate receptor activation mediates hypoxic oligodendrocyte death and axonal injury in cerebral white matter. J. Neurosci. 21 (2001) 4237-4248
106. Terry L.J., Shows E.B., and Wente S.R. Crossing the nuclear envelope: hierarchical regulation of nucleocytoplasmic transport. Science 318 (2007) 1412-1416
107. Trushina E., Heldebrant M.P., Perez-Terzic C.M., Bortolon R., Kovtun I.V., Badger II J.D., Terzic A., Estevez A., Windebank A.J., Dyer R.B., Yao J., and McMurray C.T. Microtubule destabilization and nuclear entry are sequential steps leading to toxicity in Huntington's disease. Proc. Natl. Acad. Sci. U.S.A. 100 (2003) 12171-12176
108. Trushina E., Dyer R.B., Badger II J.D., Ure D., Eide L., Tran D.D., Vrieze B.T., Legendre-Guillemin V., McPherson P.S., Mandavilli B.S., Van Houten B., Zeitlin S., McNiven M., Aebersold R., Hayden M., Parisi J.E., Seeberg E., Dragatsis I., Doyle K., Bender A., Chacko C., and McMurray C.T. Mutant huntingtin impairs axonal trafficking in mammalian neurons in vivo and in vitro. Mol. Cell Biol. 24 (2004) 8195-8209
109. 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., and 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. Gen. 9 (2000) 503-513
110. Velier J., Kim M., Schwarz C., Kim T.W., Sapp E., Chase K., Aronin N., and DiFiglia M. Wild-type and mutant huntingtin function in vesicle trafficking in the secretory and endocytotic pathways. Exper. Neurol. 152 (1998) 34-40
111. Wang C.E., Zhou H., McGuire J.R., Cerullo V., Lee B., Li S.H., and Li X.L. Suppression of neuropil aggregates and neurological symptoms by an intracellular antibody implicates the cytoplasmic toxicity of mutant huntingtin. J. Cell Biol. 181 (2008) 803-816
112. Watase K., Venken K.J.T., Sun Y., Orr H.T., and Zoghbi H.Y. Regional differences of somatic CAG repeat instability do not account for selective neuronal vulnerability in a knock-in mouse model of SCA1. Hum. Mol. Gen. 12 (2003) 2789-2795
113. Weiss A., Klein C., Woodman B., Sathasivam K., Bibel M., Regulier E., Bates G.P., and Paganetti P. Sensitive biochemical aggregate detection reveals aggregation onset before symptom development in cellular and murine models of Huntington's disease. J. Neurochem. 104 (2008) 846-858
114. Wojaczynska-Stanek K., Adamek D., Marsza E., and Hoffman-Zacharska D. Huntington Disease in a 9-year-old boy: Clinical course and neuropathologic examination. J. Child. Neurol. 21 (2006) 1068-1073
115. Wolf H.K., Buslei R., Schmidt-Kastner R., Schmidt-Kastner P.K., Pietsch T., Wiestler O.D., and Bluhmke I. NeuN: a useful neuronal marker for diagnostic histopathology. J. Histochem. Cytochem. 44 (1996) 1167-1171
116. Yang W., Dunlap J.R., Andrews R.B., and Wetzel R. Aggregated polyglutamine peptides delivered to nuclei are toxic to mammalian cells. Hum. Mol. Gen. 11 (2002) 2905-2917
117. Yu Z.X., Li S.H., Evans J., Pillariseti A., Li H., and Li X.J. Mutant huntingtin causes context-dependent neurodegeneration in mice with Huntington's disease. J. Neurosci. 23 (2003) 2193-2202
118. Zhang R., and Oorschot D.E. Total number of neurons in the habenular nuclei of the rat epithalamus, a stereological study. J. Anat 208 (2006) 577-585
119. Zoghbi H.Y., and Orr H.T. Glutamine repeats and neurodegeneration. Ann. Rev. Neurosci. 23 (2000) 217-247