Expanded polyglutamines induce neurodegeneration and trans-neuronal alterations in cerebellum and retina of SCA7 transgenic mice

Among the eight progressive neurodegenerative diseases caused by polyglutam ine expansions, spinocerebellar ataxia type 7 (SCA7) is the only one to dis play degeneration in both brain and retina, We show here that mice overexpr essing full-length mutant ataxin-7[Q90] either in Purkinje cells or in rod photoreceptors have deficiencies in motor coordination and vision, respecti vely. In both models, although with different time courses, an N-terminal f ragment of mutant ataxin-7 accumulates into ubiquitinated nuclear inclusion s that recruit a distinct set of chaperone/proteasome subunits, A severe de generation is caused by overexpression of ataxin-7[Q90] in rods, whereas a similar overexpression of normal ataxin-7[Q10] has no obvious effect, The d egenerative process is not limited to photoreceptors, showing secondary alt erations of post-synaptic neurons, These findings suggest that proteolytic cleavage of mutant ataxin-7 and trans-neuronal responses are implicated in the pathogenesis of SCA7.