Reversal of neuropathology and motor dysfunction in a conditional model of Huntington's disease
- PMID: 10778856
- DOI: 10.1016/S0092-8674(00)80623-6
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.
Comment in
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Reversing neurodegeneration: a promise unfolds.Cell. 2000 Mar 31;101(1):1-4. doi: 10.1016/S0092-8674(00)80617-0. Cell. 2000. PMID: 10778849 Review. No abstract available.
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