title: Reversal of neuropathology and motor dysfunction in a conditional model of Huntington's disease.
abstract: Neurodegenerative disorders like Huntington's disease (HD) are characterized by progressive and putative irreversible clinical and neuropathological symptoms, including neuronal protein aggregates. Conditional transgenic models of neurodegenerative diseases therefore could be a powerful means to explore the relationship between mutant protein expression and progression of the disease. We have created a conditional model of HD by using the tet-regulatable system. Mice expressing a mutated huntingtin fragment demonstrate neuronal inclusions, characteristic neuropathology, and progressive motor dysfunction. Blockade of expression in symptomatic mice leads to a disappearance of inclusions and an amelioration of the behavioral phenotype. We thus demonstrate that a continuous influx of the mutant protein is required to maintain inclusions and symptoms, raising the possibility that HD may be reversible.
authors.affiliation: Center for Neurobiology and Behavior, Columbia University, New York, New York 10032, USA.
authors.forename: A
authors.initials: A
authors.lastname: Yamamoto
authors.forename: J J
authors.initials: JJ
authors.lastname: Lucas
authors.forename: R
authors.initials: R
authors.lastname: Hen
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D019957:Motor Skills Disorders / Q000235:genetics / Q000473:pathology / Q000628:therapy; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype
chemical_list: C086055:HTT protein, human; C506812:Htt protein, mouse; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010455:Peptides; C097188:polyglutamine