Figure 3. AtmR35X/R35X; Aptx−/− mice develop a progressive loss in motor coordination.
(A) AtmR35X/R35X; Aptx−/− mice take a similar amount of time to descend a vertical pole at P45, P120, and P210, but significantly longer at P400. These overall results were found to be similar for both male (left, n=2–12) and female (right, n=4–12) mice. (B) Consistent with the vertical pole test, the gait of AtmR35X/R35X; Aptx−/− mice measured during ambulation on a Catwalk gait analysis system was significantly different to controls by P400, but not before P210. This includes the percent of time a mouse spends with 3 versus 1, 2, or 4 paws on the ground and the speed and cadence during each run across the platform. The effects of the two null mutations were generally similar between males (left, n=4–21) and females (right, n=3–18). (C) Behavioral data for male (blue) and female (pink) AtmR35X/R35X; Aptx−/− (dark purple, left) and Atm+/+; Aptx+/+ (orange, right) mice are plotted at P30 (left two columns) and P400 (right two columns). Left-right asymmetries of the horizontal bars indicate a difference in performance between genotypes for the behavioral test listed in a column on the far left. A significant difference in the time to right during the righting reflex at P8 was observed in both male and female mice (bottom). (A) and (B) were examined via two-way ANOVA with age and genotype as factors followed by Tukey’s multiple comparison tests between AtmR35X/R35X; Aptx−/− and each of the control genotypes. Behavioral tests in (C) were examined using a non-parametric Kruskal-Wallis followed by Dunn’s multiple comparisons tests. Symbol/color key: Atm+/+; Aptx+/+ (purple circle), Atm+/+; Aptx−/− (blue diamond), AtmR35X/R35X; Aptx+/+ (green triangle), AtmR35X/R35X; Aptx−/− (orange square), AtmR35X/+; Aptx−/− (red inverted triangle).
Figure 3—figure supplement 1. AtmR35X/R35X; Aptx−/− mice develop progressive ataxia.
