Figure 4.
Behavioral and motor deficits of SCA7 mice. A-E, Open field analyses show that SCA7140Q/5Q males (n = 6) progressively become hypoactive relative to WT male littermates (n = 6), according to the distance traveled (genotypes: F(1,5) = 82.21, p = 0.0001; A), the resting time (genotypes: F(1,5) = 43.32, p = 0.0001; B), the average speed (genotypes: F(1,5) = 64.12, p = 0.0005; C), and the number (Nb) of rears (genotypes: F(1,5) = 11.71, p = 0.0188; D). However, SCA7 mice show no difference with WT mice as for the time spent in the arena center (genotypes: F(1,5) = 0.26, p = 0.6307) (E). Accelerating rotarod (mean latency to fall) shows progressive motor deficit of SCA7140Q/5Q males compared with WT males (genotypes: F(1,5) = 6.61, p = 0.0499; F). Notched bar [time to cross the bar (genotypes: F(1,123) = 27.96, p < 0.0001; G) and number of mistakes (genotypes: F(1,123) = 29.78, p < 0.0001; H)] indicates that SCA7140Q/5Q males (n = 10) progressively have altered motor coordination and balance compared with WT males (n = 12). Beam walking also shows that motor performances of SCA7140Q/5Q males (n = 10) mice are affected compared with WT males (n = 12) (genotypes: F(1,123) = 13.60, p = 0.0015; I). Spatial gait analysis using footprint patterns indicates that SCA7140Q/5Q males (n = 9-11) progressively have shorter stride length of the four limbs [only right forelimb shown (genotypes: F(1,74) = 4.75, p = 0.0325; J) and shorter stance width (only forelimbs shown (genotypes: F(1,74) = 10.11, p = 0.0021; K))] compared with WT littermates (n = 9-12). Temporal gait analysis using Catwalk shows that swing times of forelimbs [average of right and left forelimbs (genotypes: F(1,26) = 19.17, p = 0.0004; L), but not hindlimbs (average of right and left hindlimbs (genotypes: F(1,26) = 0.92, p = 0.3458; M)] of SCA7140Q/5Q males (n = 15) progressively become slower than those of WT males (n = 10). Grip strength performance of SCA7140Q/5Q males (n = 6) normalized to mouse body weight is similar to WT males (n = 6) (genotypes: F(1,40) = 0.19, p = 0.6613; N). O-S, Sixteen-week-old SCA7140Q/5Q females (SCA7-F) (n = 7) are hypoactive relative to WT female littermates (WT-F) (n = 11) in open field test, according to the distance traveled (O), resting time (P), average speed (Q), and Nb of rears (R), and 25-week-old SCA7-F (n = 7) show motor defect in rotarod relative to WT-F (n = 11) (S). Data are mean ± SEM. Two-way ANOVA with repeated measurement (A-F,I,L-N) or ordinary two-way ANOVA (G,H,J,K), followed by post hoc Bonferroni test: *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001; two-tailed Student's t test (O-S).