| Description: |
The Machado-Joseph disease (MJD; MIM 109150), also known as spinocerebellar ataxia 3 (SCA3), is a late-onset, dominantly inherited disorder presenting with gait disturbance due to defects in motor neuron activity worldwide. Clinical neurological presentation is in the third to fifth decade of life and includes gait ataxia, dysarthria, dysmetria, pyramidal signs, hyperreflexia, dystonia and opthalmoplegia. Neuropathologically, MJD is characterized by neuronal loss and gliosis in the dentate nucleus, vestibular nuclei, spinocerebellar tracts, substansia nigra and other nuclei of the basal ganglia and axonal neuropathy of peripheral motor and sensory axons. Molecular analysis has shown that MJD is caused by a pathological expansion of a CAG repeat in exon 10 of the MJD1 gene encoding ataxin-3, a protein of unknown function. The CAG repeats range from 12 to 37 in the normal population and from 55 to 86 in MJD patients. The SCA3 mouse was created carrying the full-length MJD1 gene with expanded polyglutamine tracts and all the enhancers and long-range regulatory elements needed for cell-specific expression at physiological levels. This mouse model is an invaluable resource for the detailed analysis of the neurodegenerative processes underlying MJD pathogenesis and a useful reagent to test the efficacy of new therapeutic strategy and other polyglutamine disorders, such as Huntington's Disease.
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