Allele specific silencing of mutant ataxin-3 prevents the appearance of balance and motor coordination abnormalities.

<p>(a) Time course of mice behavior tests: rotarod performance test, footprints patterns analysis and activity box monitoring. (b) Rotarod test. Mice were placed in a rotarod accelerating from 0 to 40 r.p.m. in 5 min. Mice co-injected with Atx3 MUT and shAtx3 (closed circles, <i>n</i> = 8) showed an improvement performance relative to mice co-injected with Atx3 MUT and shGFP (control) (open circles, <i>n</i> = 7), especially at 8 and 10 weeks post-injection. Wild-type non-injected mice are represented as WT (<i>n</i> = 8). Values are expressed as mean ± SEM. *<i>P</i><0.05 (2-way ANOVA Bonferroni <i>post</i>-test). (c–f) Footprint analysis of shAtx3 and shGFP-treated Atx3 MUT mice. (c) Stride length. Mice injected with RNA interference against mutant ataxin-3 (MUT+shAtx3) have an increased stride length relative to control (MUT+shGFP) starting at 6 weeks post-injection. Values are expressed as mean ± SEM. *<i>P</i><0.05, **<i>P</i><0.01, ***<i>P</i><0.001 (2-way ANOVA Bonferroni <i>post</i>-test). (d) Footprint overlap. The distance between the front and hind footprint placement or overlap is reduced in shAtx3-injected mice relative to control, starting at 6 weeks post-injection. Values are expressed as mean ± SEM. *<i>P</i><0.05, **<i>P</i><0.01 (2-way ANOVA Bonferroni <i>post</i>-test). (e) Hind base width. The shAtx3-injected mice have a narrow hind base width relative to control, starting at 6 weeks post-injection. Values are expressed as mean ± SEM. *<i>P</i><0.05, **<i>P</i><0.01 (2-way ANOVA Bonferroni <i>post</i>-test). (f) Front base width. The shAtx3-injected mice have a narrow front base width relative to control, starting at 8 weeks post-injection. Values are expressed as mean ± SEM. *<i>P</i><0.05 (2-way ANOVA Bonferroni <i>post</i>-test). In general the patterns clearly differ, showing that shAtx3-injected mice display longer strides, evenly spaced and accurately positioned footprints when compared to control-treated MJD mice.