Figure 2. Constitutive phosphorylation of HTT at S421 impairs motor skill learning in mice.

(A) Schematic of the accelerating rotarod protocol assessing motor skill learning over 8 days with 10 sessions per day. (B) Mean latency to fall each day for 8 days, for HTT-SD mice (*p<0.05: two-way ANOVA followed by Sidak’s multiple comparisons test where p<0.01 at day 7) and HTT-SA mice (ns: non-significant: two-way ANOVA). (C) Mean time to fall off the rotarod per session, over 10 sessions, during the first or (D) the last day for HTT-SD (ns: non-significant: two-way ANOVA at day 1 and *p<0.05: two-way ANOVA at day 8 followed by Sidak’s multiple comparison test where p<0.01 at trials 3 and 10) and HTT-SA (ns: non-significant: two-way ANOVA at days 1 and 8). We compared 3-month-old male mice: 20 wild-type (WT) with 20 HTT-SD littermates, and 13 WT with 18 HTT-SA littermates.

Figure 2—figure supplement 1. HTT phosphorylation at S421 impairs motor skill learning without affecting motor performance.

(A) Results of the first rotarod trial of the first day for HTT-SD and HTT-SA mice (ns: non-significant, Mann-Whitney test). The box-whisker plots show the median, the 25th and the 75th percentiles, the smallest and the largest values for N=20 wild-type (WT) vs. 20 HTT-SD and 13 WT vs. 18 HTT-SA 3-month-old littermate male mice. (B) Performance during the 10 sessions of the first day for 8 WT, 10 HTT-SD, and 12 HTT-SA 18-month-old mice. Significance was determined using two-way ANOVA followed by Holm-Sidak’s multiple comparison test (*p<0.05 between WT and HTT-SD).