Figure 3

DCC is required for asymmetric movements. We used behavioral tests to investigate the motor phenotype of Dcc ^kanga/− mutant mice. Dcc ^kanga/− mice (n = 11; black and red) were compared to Dcc ^+/+ mice or Dcc ^kanga/+ mice (that behave like wildtype mice, n = 17; gray). Five of the 11 Dcc ^kanga/− mice displayed marked balance disorders (red): they were unable to stand on their limbs and thus moved very little in the open-field test (ANOVA F_(2,25) = 33.18, p < 0.001, followed by the Bonferroni post hoc test; B). Because they were unable to perform most of the motor tests, they were excluded from further analysis. Dcc ^kanga/− mice were lighter than their littermate controls (ANOVA F_(2,20) = 6.27, p = 0.008, followed by the Bonferroni post hoc test; A) and were accordingly weaker in the muscle strength test (Student’s test, p_forelimbs = 0.228; p_hindlimbs = 0.042; C). Dcc ^kanga/− mice were indistinguishable from controls in the Rotarod test (repeated-measures ANOVA with two factors. F_(1,21) = 0.71, p = 0.793, followed by the Bonferroni post hoc test; D). On the treadmill, Dcc ^kanga/− mice displayed a striking hopping gait, frequently moving both their forelimbs and their hindlimbs simultaneously (Mann-Whitney test, p_forelimbs < 0.0001; p_hindlimbs < 0.0001; E, E2). In contrast, control mice made alternating movements (E, E1) of their forelimbs and hindlimbs. In the ladder test, Dcc ^kanga/− mice made more forelimb errors than the controls (Freeman-Halton extension of Fisher’s exact test, p = 0.038; F). When placed in a new walled environment, mice have a tendency to establish contacts on the walls with their forelimbs in an asymmetric (G1, control mice) or symmetric (G2, Dcc ^kanga/− mice) manner. In the reaching test, Dcc ^kanga/− mice made more symmetric forelimb movements than the controls (Student’s test, p < 0.0001; G).