CHIP-T246M in rodents resulted in progressive ataxia and altered gait.

Changes in (A) rotatrod performance, (B) support base, (C) stride, and (D) support ratio over time in rats with the indicated genotypes represented by line plot and summarized by the mean ± SEM (N = 6 animals/genotype), Tukey’s post hoc test: a, b, c, and ††† correspond to p E) Graphical representation of gait parameters with foot locations indicated (RH = right hand, RF = right foot, LH = left hand, LF = left foot). (F) Rotarod analysis during the initial learning phase (left) or over time (right) represented by a line graph of the change in latency to fall over the first three trials, including a re-test (R) two days later, summarized by the mean ± SEM (N = 10–20 animals/genotype), Dunnett’s post hoc test: #, ## correspond to p p p G) The initial rotarod performance in CHIP null mice (−/−) or wild-type mice (+/+) over the first three trials, including a re-test (R) two days later, summarized by the mean ± SEM (N = 10 animals/genotype), Tukey’s post hoc test: ‡ corresponds to p p H) Composite ataxia score of mice with the indicated genotypes including wild-type (+/+), heterozygous (+/−), and homozygous (−/−) knockouts of the CHIP allele represented by scatterplot and summarized by the mean ± SEM (N = 12 animals/genotype). Results of the linear regression analysis are depicted by the line and equation provided and results of the mixed model analysis provided. In comparing slopes, only M/M mice had a different slope at α = 0.05.