Motor impairment in MI2 mice. a C57Bl/6S and MI2 mice were analyzed using accelerating rotarod test at 6, 12, 15 and 20 months of age (mean latency to fall from the rod ± SEM, n = 12–18 mice per group). A main effect of age was identified by two-way ANOVA. Statistically significant differences between 6 and 20 months (###p < 0.001) and 12 and 20 months (‡‡‡p < 0.001) in MI2 mice, and between MI2 and C57Bl/6S animals at 20 months (*p < 0.05) were revealed by multiple comparisons with Bonferroni correction. b Motor performance of 20 month-old mice was tested using the static rod test (mean orientation time or mean transit time ± SEM, n = 13–18 mice). No differences were identified between experimental groups using a 25 mm rod or in orientation time using a 15 mm rod, but there was a statistically significant difference in transit time on the 15 mm rod between MI2 and C57Bl/6S mice (*p < 0.05, t test). c Gait pattern of mice was analyzed between 3 and 18 months of age using DigiGait test (see also Supplementary Fig. S7, Online Resource 1). Alterations in individual gait phases were found in MI2 animals compared to control C57Bl/6S mice (mean ± SEM, n = 9–17 male mice per group). Two-way ANOVA identified a main effect of age on forelimb stance and swing duration, and on hindlimb propulsion duration, a main effect of genotype on forelimb stride length and stance, swing and propulsion duration, and two-way interaction between age and genotype for forelimb propulsion duration. Statistically significant differences were identified at 9, 12 and 18 months for forelimb stride length and stance, swing and propulsion duration, and at 18 months for hindlimb propulsion duration (*p < 0.05; **p < 0.01, ***p < 0.001) by pairwise comparisons with Bonferroni correction between MI2 and C57Bl/6S mice (see detailed statistical evaluation in Online Resource)