Light and electron microscopic characterization of the evolution of cellular pathology in Hdh Q92 Huntington's disease knock-in mice

Brain Research Bulletin

Volumn 88, Issue 2-3, 2012, Pages 171-181

  Bayram Weston, Zubeyde ^a   Jones, Lesley ^b   Dunnett, Stephen B ^a   Brooks, Simon P ^a  

^a CARDIFF UNIVERSITY   (United Kingdom)

^b CARDIFF UNIVERSITY   (United Kingdom)

Author keywords

Aggregations; Electron microscopy; HdhQ92 Q92 knock in mouse line; Huntington's disease; Inclusions

Indexed keywords

HUNTINGTIN; MUTANT PROTEIN;

AGE; AMINO TERMINAL SEQUENCE; AMYGDALOID NUCLEUS; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; APOPTOSIS; ARTICLE; CELL DEGENERATION; CELL MEMBRANE; CELL NUCLEUS; CELL NUCLEUS INCLUSION BODY; CEREBELLUM; CONTROLLED STUDY; CORPUS STRIATUM; CYTOPLASM; CYTOSOL; DISEASE COURSE; ELECTRON MICROSCOPY; FEMALE; GENE TARGETING; GLOBUS PALLIDUS; HIPPOCAMPUS; HUNTINGTON CHOREA; HYPOTHALAMUS; LIFESPAN; MALE; MICROSCOPY; MITOCHONDRION; MOTOR CORTEX; MOUSE; NERVE CELL; NONHUMAN; NUCLEUS ACCUMBENS; OLFACTORY BULB; PRIORITY JOURNAL; PROTEIN AGGREGATION; PYRIFORM CORTEX; SENSORY CORTEX; SEPTUM PELLUCIDUM; THALAMUS;

ANIMALS; BRAIN; DISEASE MODELS, ANIMAL; FEMALE; GENE KNOCK-IN TECHNIQUES; GLIAL FIBRILLARY ACIDIC PROTEIN; HUNTINGTON DISEASE; MALE; MICE; MICE, INBRED C57BL; MICE, TRANSGENIC; MICROSCOPY, ELECTRON; NERVE TISSUE PROTEINS; NEURONS; NUCLEAR PROTEINS;

EID: 84860841192     PISSN: 03619230     EISSN: 18732747     Source Type: Journal    
DOI: 10.1016/j.brainresbull.2011.03.013     Document Type: Article

References (63)

1. Abercrombie M. Estimation of nuclear population from microtome sections. Anatomical Records 1946, 239-247.
2. Bates G.P., Harper P.S., Jones L. Huntington's Disease 2002, Oxford University Press. G.P. Bates, P.S. Harper, L. Jones (Eds.).
3. Z. Bayram-Weston, L. Jones, S.B. Dunnett, S.P. Brooks, Light and electron microscopic characterization of the evolution of cellular pathology in the R6/1 transgenic mouse., Brain Res. Bull., in this issue (2010).
4. Z. Bayram-Weston, L. Jones, S.B. Dunnett, S.P. Brooks, Light and electron microscopic characterization of the evolution of cellular pathology in YAC128 transgenic mice, Brain Res. Bull., in this issue.
5. Z. Bayram-Weston, E.M. Torres, L. Jones, S.B. Dunnett, Brooks S.P. Light and electron microscopic characterization of the evolution of cellular pathology in the Hdh(CAG)150 Huntington's disease knock-in mouse, Brain Res. Bull., in this issue.
6. Brooks S., Higgs G., Jones L., Dunnett S.B. Longitudinal analysis of the behavioural phenotype in Hdh(Q92) Huntington's disease knock-in mice. Brain Res. Bull. 2010, 10.1016/j.brainresbull.2010.05.003.
7. Cattaneo E., Calabresi P. Mutant huntingtin goes straight to the heart. Nat. Neurosci. 2002, 5:711-712.
8. 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.
9. DiFiglia M., Sapp E., Chase K., Schwarz C., Meloni A., Young C., Martin E., Vonsattel J.P., Carraway R., Reeves S.A. Huntingtin is a cytoplasmic protein associated with vesicles in human and rat brain neurons. Neuron 1995, 14:1075-1081.
10. DiFiglia M., Sapp E., Chase K.O., Davies S.W., Bates G.P., Vonsattel J.P., Aronin N. Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science 1997, 277:1990-1993.
11. Ferrante R.J., Gutekunst C.A., Persichetti F., McNeil S.M., Kowall N.W., Gusella J.F., MacDonald M.E., Beal M.F., Hersch S.M. Heterogeneous topographic and cellular distribution of huntingtin expression in the normal human neostriatum. J. Neurosci. 1997, 17:3052-3063.
12. Gourfinkel-An I., Cancel G., Duyckaerts C., Faucheux B., Hauw J.J., Trottier Y., Brice A., Agid Y., Hirsch E.C. Neuronal distribution of intranuclear inclusions in Huntington's disease with adult onset. Neuroreport 1998, 9:1823-1826.
13. 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.
14. Gray M., Shirasaki D.I., Cepeda C., Andre V.M., Wilburn B., Lu X.H., Tao J., Yamazaki I., Li S.H., Sun Y.E., Li X.J., Levine M.S., Yang X.W. Full-length human mutant huntingtin with a stable polyglutamine repeat can elicit progressive and selective neuropathogenesis in BACHD mice. J. Neurosci. 2008, 28:6182-6195.
15. 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.
16. Hedreen J.C., Folstein S.E. Early loss of neostriatal striosome neurons in Huntington's disease. J. Neuropathol. Exp. Neurol. 1995, 54:105-120.
17. 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.
18. Hoogeveen A.T, Willemsen R., Meyer N., de Rooij K.E., Roos R.A., van Ommen G.J., Galjaard H. Characterization and localization of the Huntington disease gene product. Hum. Mol. Genet. 1993, 2:2069-2073.
19. Landles C., Bates G.P. Huntingtin and the molecular pathogenesis of Huntington's disease - fourth in molecular medicine review series 1. Embo Rep. 2004, 5:958-963.
20. Landles C., Sathasivam K., Weiss A., Woodman B., Moffitt H., Finkbeiner S., Sun B., Gafni J., Ellerby L.M., Trottier Y., Richards W.G., Osmand A., Paganetti P., Bates G.P. Proteolysis of mutant huntingtin produces an exon 1 fragment that accumulates as an aggregated protein in neuronal nuclei in Huntington disease. J. Biol. Chem. 2010, 285:8808-8823.
21. 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.
22. Li H., Li S.H., Cheng A.L., Mangiarini L., Bates G.P., Li X.J. Ultrastructural localization and progressive formation of neuropil aggregates in Huntington's disease transgenic mice. Hum. Mol. Genet. 1999, 8:1227-1236.
23. Li H., Li S.H., Johnston H., Shelbourne P.F., Li X.J. Amino-terminal fragments of mutant huntingtin show selective accumulation in striatal neurons and synaptic toxicity. Nat. Genet. 2000, 25:385-389.
24. Li J.Y., Plomann M., Brundin P. Huntington's disease: a synaptopathy?. Trends Mol. Med. 2003, 9:414-420.
25. 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.
26. Lloret A., Dragileva E., Teed A., Espinola J., Fossale E., Gillis T., Lopez E., Myers R.H., MacDonald M.E., Wheeler V.C. Genetic background modifies nuclear mutant huntingtin accumulation and HD CAG repeat instability in Huntington's disease knock-in mice. Hum. Mol. Genet. 2006, 15:2015-2024.
27. Lunkes A., Mandel J.L. A cellular model that recapitulates major pathogenic steps of Huntington's disease. Hum. Mol. Genet. 1998, 7:1355-1361.
28. 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., Roos R.A. Distribution of inclusions in neuronal nuclei and dystrophic neurites in Huntington disease brain. J. Neuropathol. Exp. Neurol. 1999, 58:129-137.
29. 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.
30. Milnerwood A.J., Cummings D.M., Dallerac G.M., Brown J.Y., Vatsavayai S.C., Hirst M.C., Rezaie P., Murphy K.P. Early development of aberrant synaptic plasticity in a mouse model of Huntington's disease. Hum. Mol. Genet. 2006, 15:1690-1703.
31. 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.
32. Ordway J.M., Tallaksen-Greene S., Gutekunst C.A., Bernstein E.M., Cearley J.A., Wiener H.W., Dure L.S., Lindsey R., Hersch S.M., Jope R.S., Albin R.L., Detloff P.J. Ectopically expressed CAG repeats cause intranuclear inclusions and a progressive late onset neurological phenotype in the mouse. Cell 1997, 91:753-763.
33. Paxinos G., Franklin K.B.J. The Mouse Brain in Stereotaxic Coordinates 2001, Academic Press, San Diego, CA. 2nd ed.
34. Reddy P.H., Williams M., Charles V., Garrett L., Pike-Buchanan L., Whetsell W.O., Miller G., Tagle D.A. Behavioural abnormalities and selective neuronal loss in HD transgenic mice expressing mutated full-length HD cDNA. Nat. Genet. 1998, 20:198-202.
35. Reddy P.H., Williams M., Tagle D.A. Recent advances in understanding the pathogenesis of Huntington's disease. Trends Neurosci. 1999, 22:248-255.
36. 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. U. S. A. 1988, 85:5733-5737.
37. Reiner A., Del Mar N., Deng Y.P., Meade C.A., Sun Z., Goldowitz D. R6/2 neurons with intranuclear inclusions survive for prolonged periods in the brains of chimeric mice. J. Comp. Neurol. 2007, 505:603-629.
38. Roos R.A., Bots G.T. Nuclear membrane indentations in Huntington's chorea. J. Neurol. Sci. 1983, 61:37-47.
39. Roos R.A., Pruyt J.F., de Vries J., Bots G.T. Neuronal distribution in the putamen in Huntington's disease. J. Neurol. Neurosurg. Psychiatry 1985, 48:422-425.
40. Rosas H.D., Koroshetz W.J., Chen Y.I., Skeuse C., Vangel M., Cudkowicz M.E., Caplan K., Marek K., Seidman L.J., Makris N., Jenkins B.G., Goldstein J.M. Evidence for more widespread cerebral pathology in early HD: an MRI-based morphometric analysis. Neurology 2003, 60:1615-1620.
41. Ross C.A. Intranuclear neuronal inclusions: a common pathogenic mechanism for glutamine-repeat neurodegenerative diseases?. Neuron 1997, 19:1147-1150.
42. Sapp E., Schwarz C., Chase K., Bhide P.G., Young A.B., Penney J., Vonsattel J.P., Aronin N., DiFiglia M. Huntingtin localization in brains of normal and Huntington's disease patients. Ann. Neurol. 1997, 42:604-612.
43. Saudou F., Finkbeiner S., Devys D., Greenberg M.E. Huntingtin acts in the nucleus to induce apoptosis but death does not correlate with the formation of intranuclear inclusions. Cell 1998, 95:55-66.
44. 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. Widespread expression of Huntington's disease gene (IT15) protein product. Neuron 1995, 14:1065-1074.
45. Singaraja R.R., Hadano S., Metzler M., Givan S., Wellington C.L., Warby S., Yanai A., Gutekunst C.A., Leavitt B.R., Yi H., Fichter K., Gan L., McCutcheon K., Chopra V., Michel J., Hersch S.M., Ikeda J.E., Hayden M.R. HIP14, a novel ankyrin domain-containing protein, links huntingtin to intracellular trafficking and endocytosis. Hum. Mol. Genet. 2002, 11:2815-2828.
46. Sisodia S.S. Nuclear inclusions in glutamine repeat disorders: are they pernicious, coincidental, or beneficial?. Cell 1998, 95:1-4.
47. 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.
48. Tellez-Nagel I., Johnson A.B., Terry R.D. Studies on brain biopsies of patients with Huntington's chorea. J. Neuropathol. Exp. Neurol. 1974, 33:308-332.
49. 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.
50. Trueman R.C., Brooks S.P., Jones L., Dunnett S.B. The operant serial implicit learning task reveals early onset motor learning deficits in the Hdh knock-in mouse model of Huntington's disease. Eur. J. Neurosci. 2007, 25:551-558.
51. Trueman R.C., Brooks S.P., Jones L., Dunnett S.B. Time course of choice reaction time deficits in the Hdh(Q92) knock-in mouse model of Huntington's disease in the operant serial implicit learning task (SILT). Behav. Brain Res. 2008, 189:317-324.
52. Trueman R.C., Brooks S.P., Jones L., Dunnett S.B. Rule learning, visuospatial function and motor performance in the Hdh(Q92) knock-in mouse model of Huntington's disease. Behav. Brain Res. 2009, 203:215-222.
53. Trushina E., Dyer R.B., Badger 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., McMurray C.T. Mutant huntingtin impairs axonal trafficking in mammalian neurons in vivo and in vitro. Mol. Cell Biol. 2004, 24:8195-8209.
54. Turmaine M., Raza A., Mahal A., Mangiarini L., Bates G.P., Davies S.W. Nonapoptotic neurodegeneration in a transgenic mouse model of Huntington's disease. Proc. Natl. Acad. Sci. U. S. A. 2000, 97:8093-8097.
55. Van Raamsdonk J.M., Metzler M., Slow E., Pearson J., Schwab C., Carroll J., Graham R.K., Leavitt B.R., Hayden M.R. Phenotypic abnormalities in the YAC128 mouse model of Huntington disease are penetrant on multiple genetic backgrounds and modulated by strain. Neurobiol. Dis. 2007, 26:189-200.
56. Vonsattel J.P., DiFiglia M. Huntington disease. J. Neuropathol. Exp. Neurol. 1998, 57:369-384.
57. 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.
58. Waelter S., Boeddrich A., Lurz R., Scherzinger E., Lueder G., Lehrach H., Wanker E.E. Accumulation of mutant huntingtin fragments in aggresome-like inclusion bodies as a result of insufficient protein degradation. Mol. Biol. Cell 2001, 12:1393-1407.
59. Weiss A., Roscic A., Paganetti P. Inducible mutant huntingtin expression in HN10 cells reproduces Huntington's disease-like neuronal dysfunction. Mol. Neurodegener. 2009, 4:11.
60. Wheeler V.C., Auerbach W., White J.K., Srinidhi J., Auerbach A., Ryan A., Duyao M.P., Vrbanac V., Weaver M., Gusella J.F., Joyner A.L., MacDonald M.E. Length-dependent gametic CAG repeat instability in the Huntington's disease knock-in mouse. Hum. Mol. Genet. 1999, 8:115-122.
61. 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.
62. White J.K., Auerbach W., Duyao M.P., Vonsattel J.P., Gusella J.F., Joyner A.L., MacDonald M.E. Huntingtin is required for neurogenesis and is not impaired by the Huntington's disease CAG expansion. Nat. Genet. 1997, 17:404-410.
63. Yamamoto A., Lucas J.J., Hen R. Reversal of neuropathology and motor dysfunction in a conditional model of Huntington's disease. Cell 2000, 101:57-66.