Lessons from animal models of Huntington's disease

Trends in Genetics

Volumn 18, Issue 4, 2002, Pages 202-209

  Rubinsztein, David C ^a  

^a WELLCOME TRUST SANGER INSTITUTE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLIC AMP RESPONSIVE ELEMENT BINDING PROTEIN BINDING PROTEIN; GENE PRODUCT; HUNTINGTIN; MINOCYCLINE; MUTANT PROTEIN;

AMINO TERMINAL SEQUENCE; ANIMAL MODEL; BIOLOGICAL MODEL; CAENORHABDITIS ELEGANS; CELL DEATH; CELL FUNCTION; CLINICAL FEATURE; DEGENERATIVE DISEASE; DROSOPHILA; ENERGY YIELD; GENE EXPRESSION; GENE FUNCTION; GENE LOCUS; GENE MUTATION; GENETIC GAIN; HUMAN; HUNTINGTON CHOREA; NEUROPATHOLOGY; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN FUNCTION; REVIEW; RNA TRANSLATION; TRANSGENIC MOUSE; TRINUCLEOTIDE REPEAT;

ANIMALS; DISEASE MODELS, ANIMAL; HUMANS; HUNTINGTON DISEASE; INCLUSION BODIES; MICE; MICE, KNOCKOUT; NERVE TISSUE PROTEINS; NEURONS; NUCLEAR PROTEINS; TANDEM REPEAT SEQUENCES; UBIQUITIN;

ANIMALIA; CAENORHABDITIS; CAENORHABDITIS ELEGANS; MUS MUSCULUS;

EID: 0036533795     PISSN: 01689525     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0168-9525(01)02625-7     Document Type: Review

References (71)

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3. Phenotypic characterisation 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
4. The molecular biology of Huntington's disease
5. Inactivation of the mouse Huntington's disease gene homolog Hdh
6. Targeted disruption of the Huntington's disease gene results in embryonic lethality and behavioural and morphological changes in heterozygotes
7. Increased apoptosis and early embryonic lethality in mice nullizygous for the Huntington's disease gene homolog
8. Huntingtin is required for neurogenesis and is not impaired by the Huntington's disease CAG expansion
9. Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice
10. A YAC mouse model for Huntington's disease with full-length mutant huntingtin, cytoplasmic toxicity, and selective striatal neurodegeneration
11. Intranuclear inclusions and neuritic aggregates in transgenic mice expressing a mutant N-terminal fragment of huntingtin
12. Behavioural abnormalities and selective neuronal loss in HD transgenic mice expressing mutated full-length HD cDNA
13. Reversal of neuropathology and motor dysfunction in a conditional model of Huntington's disease
14. Changes in cortical and striatal neurons predict behavioural and electrophysiological abnormalities in a transgenic murine model of Huntington's disease
15. A Huntington's disease CAG expansion at the murine Hdh locus is unstable and associated with behavioural abnormalities in mice
16. Enhanced sensitivity to N-methyl-d-aspartate receptor activation in transgenic and knockin mouse models of Huntington's disease
17. Age-dependent and tissue-specific CAG repeat instability occurs in mouse knock-in for a mutant Huntington's disease gene
18. Neurological abnormalities in a knock-in mouse model of Huntington's disease
19. Ectopically expressed CAG repeats cause intranuclear inclusions and a progressive late onset neurological phenotype in the mouse
20. Loss of huntingtin-mediated BDNF gene transcription in Huntington's disease
21. The huntingtin interacting protein HIP1 is a clathrin and alpha-adaptin-binding protein involved in receptor-mediated endocytosis
22. HIP1 functions in clathrin-mediated endocytosis through binding to clathrin and AP2
23. The actin-binding protein Hip1R associates with clathrin during early stages of endocytosis and promotes clathrin assembly in vitro
24. Inactivation of Hdh in the brain and testis results in progressive neurodegeneration and sterility in mice
25. Wild-type huntingtin protects from apoptosis upstream of caspase-3
26. Huntingtin's neuroprotective activity occurs via inhibition of procaspase-9 processing
27. Wild-type huntingtin reduces the cellular toxicity of mutant huntingtin in vivo
28. Wild-type huntingtin reduces the cellular toxicity of mutant huntingtin in mammalian cell models of Huntington's disease
29. Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation
30. Intranuclear neuronal inclusions in Huntington's disease and dentatorubral pallidoluysian atrophy: Correlation between the density of inclusions and IT15 CAG triplet repeat length
31. Expanded polyglutamines in Caenorhabditis elegans cause axonal abnormalities and severe dysfunction of PLM mechanosensory neurons without cell death
32. Huntingtin aggregate-associated axonal degeneration is an early pathological event in Huntington's disease mice
33. Chaperone suppression of aggregation and altered subcellular proteasome localization imply protein misfolding in SCA1
34. Bacterial and yeast chaperones reduce both aggregate formation and cell death in mammalian cell models of Huntington's disease
35. Huntingtin acts in the nucleus to induce apoptosis but death does not correlate with the formation of intranuclear inclusions
36. Mutation of the E6-AP ubiquitin ligase reduces nuclear inclusion frequency while accelerating polyglutamine-induced pathology in SCA1 mice
37. Ataxin-1 nuclear localization and aggregation: Role in polyglutamine-induced disease in SCA1 transgenic mice
38. The role of ataxin-1 nuclear expression and aggregates in SCA1 pathogenesis
39. Glutamine repeats and neurodegenerative diseases: Molecular aspects
40. Inhibiting caspase cleavage of huntingtin reduces toxicity and aggregate formation in neuronal and nonneuronal cells
41. Tissue-specific proteolysis of Huntingtin (htt) in human brain: Evidence of enhanced levels of N- and C-terminal htt fragments in Huntington's disease striatum
42. Long glutamine tracts cause nuclear localization of a novel form of huntingtin in medium spiny striatal neurons in HdhQ92 and HdhQ111 knock-in mice
43. Amino-terminal fragments of mutant huntingtin show selective accumulation in striatal neurons and synaptic toxicity
44. Mutant protein in Huntington disease is resistant to proteolysis in affected brain
45. NMDA receptor losses in putamen from patients with Huntington's disease
46. Mutant huntingtin enhances excitotoxic cell death
47. Oxidative damage to mitochondrial DNA in Huntington's disease parietal cortex
48. Biochemical abnormalities and excitotoxicity in Huntington's disease brain
49. Mitochondrial dysfunction and free radical damage in the Huntington R6/2 transgenic mouse
50. Cellular defects and altered gene expression in PC12 cells stably expressing mutant huntingtin
51. Early degenerative changes in transgenic mice expressing mutant huntingtin involve dendritic abnormalities but no impairment of mitochondrial energy production
52. Mice transgenic for the Huntington's disease mutation are resistant to chronic 3-nitropropionic acid-induced striatal toxicity
53. Partial resistance to malonate-induced striatal cell death in transgenic mouse models of Huntington's disease is dependent on age and CAG repeat length
54. Transgenic mice expressing a Huntington's disease mutation are resistant to quinolinic acid-induced striatal excitotoxicity
55. Mice transgenic for the human Huntington's disease mutation have reduced sensitivity to kainic acid toxicity
56. Polyglutamine expansions cause decreased CRE-mediated transcription and early gene expression changes prior to cell death in an inducible cell model of Huntington's disease
57. Early alterations in gene expression and cell morphology in a mouse model of Huntington's disease
58. Decreased expression of striatal signaling genes in a mouse model of Huntington's disease
59. CREB-binding protein sequestration by expanded polyglutamine
60. Expanded polyglutamine stretches interact with TAFII130, interfering with CREB-dependent transcription
61. Interference by huntingtin and atrophin-1 with cbp-mediated transcription leading to cellular toxicity
62. Histone deacetylase inhibitors arrest polyglutamine-dependent neurodegeneration in Drosophila
63. Histone deacetylase inhibitors reduce polyglutamine toxicity
64. Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease
65. Neuroprotective effects of creatine in a transgenic mouse model of Huntington's disease
66. Genetic suppression of polyglutamine toxicity in Drosophila
67. Identification of genes that modify ataxin-1-induced neurodegeneration
68. Expanded polyglutamine peptides alone are intrinsically cytotoxic and cause neurodegeneration in Drosophila
69. Suppression of polyglutamine-mediated neurodegeneration in Drosophila by the molecular chaperone HSP70
70. Over-expression of inducible HSP70 chaperone suppresses neuropathology and improves motor function in SCA1 mice
71. Genotypes at the GluR6 kainate receptor locus are associated with variation in the age of onset of Huntington's disease