Allele specific silencing of mutant ataxin-3 improves exploratory and locomotor activity and reduces anxiety in MJD transgenic mice.

<p>A) Representative plots of moved track at 10 weeks post-injection during 40 minutes in the activity box. Animals injected with shAtx3 (<i>n</i> = 8) traveled more that shGFP-injected mice (<i>n</i> = 8). The figure shows representative images that were reproducible among the different groups of animals. B–C) Locomotor horizontal activity of mice was tracked for 30 minutes (after a 10 minutes habituation period), and revealed a significantly better locomotor activity of mice injected with shAtx3 (<i>n</i> = 8) as compared to control mice (shGFP, <i>n</i> = 8), by traveling longer distances with a higher medium velocity. D–E) Two zones analysis of exploratory behavior, revealed that shAtx3-injected mice (<i>n</i> = 8) had increased exploratory behavior and were significantly less anxious than controls (shGFP; <i>n</i> = 8). F–G) This reduced anxiety of shAtx3-injected mice was confirmed through analyzis of the distance in zone two normalized with the overall distance in the arena, and also the number of entries in zone 2 normalized with the overall distance in the arena. *Statistical significance (*<i>P</i><0.05; **<i>P</i><0.01; ***<i>P</i><0.001; 2-way ANOVA, Bonferonni post-hoc test).