Figure 1

Casp2-/- mice are protected from rotarod learning and accelerating rotorod deficits in the YAC128 mice. A-B) Naïve mice were trained at 4 months of age on a fixed speed (18 RPM) rotorod; 9 trials of 2 minutes each were conducted over three days. The time to first fall and the number of falls during each trial was recorded. Casp2-/- mice are unaffected on this task, compared to WT littermates as measured by time to first fall, while YAC128 mice show significant impairment that is rescued in casp2-/-;YAC128 mice (linear mixed effects model YAC128 F(1,109) = 7.74, p = 0.0064; casp2 F(1,109) = 1.43, p = 0.23; Interaction F(1,109) = 5.36, p = 0.023) or number of total falls (linear mixed effects model YAC128 F(1,109) = 9.45, p = 0.0026; casp2 F(1,109) = 1.09, p = 0.30; Interaction F(1,109) = 3.97, p = 0.049). Data represent mean +/- SEM. N = 33 WT mice, 28 YAC128 mice, 28 casp2-/- mice and 24 casp2-/-;YAC128. C) Mice were tested on an accelerating rotorod (5-40 RPM) at 4, 8 and 12 months. Each mouse performed 3 5-minute trials and the mean of three trials recorded. YAC128 mice perform worse than WT littermates on this task (i-two-way ANOVA, YAC128 F(1,51) = 23.07, p < 0.0001, age F(2,51) = 77.92, p < 0.0001; interaction F(2,51) = 1.61, p = 0.20), while casp2-/-;YAC128 mice do not perform significantly worse than casp2-/- littermates (ii-two-way ANOVA, YAC128 F(1,45) = 2.39, p = 0.13, age F(2,45) = 18.0, p < 0.0001; interaction F(2,45) = 0.11, p = 0.89). Data represent mean +/- SEM. N = 33 WT mice, 28 YAC128 mice, 28 casp2-/- mice and 24 casp2-/-;YAC128.