Figure 4.

Excision of ataxin-7-92Q expression after symptom onset halts or reverses motor phenotypes in SCA7 transgenic mice. (A) We evaluated the neurological status of cohorts of SCA7 transgenic mice using a composite phenotype score, which consists of four individual tests that exemplify different aspects of the mouse SCA7 phenotype. Each component is scored from 0 (normal) to 3 (severely affected). The tests assess the ability to walk on a cage ledge, hindlimb clasping upon tail suspension, the existence of an abnormal gait and the development of kyphosis (hunched back secondary to neurodegeneration). Scores from all four tests are combined into a single, composite score. Using this testing paradigm, we found that after suppression of mutant ataxin-7 transgene expression at 24 weeks of age, neurological function is preserved in tamoxifen-treated bigenic mice, as they perform significantly better than oil-treated bigenic mice or SCA7 transgenic mice (P < 0.001, ANOVA with Bonferonni post-test). Error bars = SEM. (B) We employed the accelerating rotarod task to evaluate cohorts of SCA7 transgenic mice, including bigenic mice subjected to tamoxifen-induced excision of the ataxin-7-92Q transgene after symptom onset at 24 weeks, and found that treated bigenic mice perform comparably with SCA7-negative mice and significantly better than oil-treated bigenic mice at 42 weeks of age, even though bigenic mice performed significantly worse than control mice prior to treatment (*P < 0.05, ***P < 0.001, ANOVA with Bonferonni post-test). Error bars = SEM.