Fig. 5

Lentiviral-mediated MUT ATXN7 overexpression in the mouse cerebellum induces locomotor abnormalities. Performance on the accelerating rotarod showed reduced motor coordination at 8 and 12 weeks, but not at 2 or 4 weeks post-injection in mice injected with LV-MUT-ATXN7 (a-latency to fall; b-speed at falls), relative to non-injected mice or mice injected with LV-WT-ATXN7. The locotronic test shows an increased number of errors (c) and time to cross the bar (d) in mice injected with LV-MUT-ATXN7, relatively to non-injected mice or mice receiving LV-WT-ATXN7, at 8 and 12 weeks post-injection. Measure of actimetry: total active time decreased (~20 %) (e) and inactive time increased (f), but no statistically significant changes in total immobility (g) were observed in mice injected with MUT ATXN7. These mice also displayed reduced global movements (~22 %) (h), low (~20 %) (j) and high speed movements (~31.5 %) (i), average speed (~12 %) (k) and total distance traveled (~31 %) (l) during 45 min recording, compared to non-injected mice or mice injected with LV-WT ATXN7. The performances of mice injected with LV-WT-ATXN7 or non-injected mice were similar in all tests. Statistical analysis for actimetry assessment was performed using one-way ANOVA followed by a post-hoc Fisher’s test. Statistical analysis for behavior assessment in the rotarod and locotronic tests was performed using Two-way ANOVA followed by a post-hoc Fisher’s test. Number of animals; n = 6 for non-injected, n = 6 for WT ATXN7 and n = 8 for MUT ATXN7 injected mice.