
Bindarit partially improves the swimming locomotor phenotype in prh mutants. A, Both untreated WT and prh show improvement in surface righting reflex over time (****p < 0.0001) and there is no difference between WT and prh (p = 0.8627; n = 12–18 in each group, repeated measures ANOVA, followed by post hoc Sidak's test). B, There is no difference in the time for negative geotaxis between untreated WT and prh (p = 0.1914) and both genotypes have significant improvement over time between P6 and P8 (p = 0.0023; n = 12–18 in each group, repeated measures ANOVA, followed by post hoc Sidak's test). The frequency of falling from the surface during the negative geotaxis test is similar in WT (8%) and prh mutants (10%). C, During swim testing, untreated prh show significantly longer “time without hindlimb alternation” or spastic time, relative to WT, both in first trials and second trials on putting prh into the warm water (****p < 0.0001 for first trial, *p = 0.0235 for second trial, n = 12–15 in each group, Student's t test). D, Frequency of alternating hindlimbs is significantly less in prh relative to WT (****p < 0.0001 for first trial, *p = 0.0127 for second trial, Student's t test). E, Vehicle-treated (veh-)prh show significantly longer time without hindlimb alternation, relative to veh-WT (††††p < 0.0001), and bindarit treatment significantly improved and shortened this spastic time compared with veh-prh, in the first trials (**p = 0.0086, one-way ANOVA followed by post hoc Sidak's test, n = 8–13 in each group), but there is no significant difference among the groups in the second trials (p = 0.2647, one-way ANOVA). F, There is no difference among veh-WT, veh-prh, and bin-prh in the frequency of alternating hindlimbs, excluding the time without hindlimb alternation, in the first (p = 0.3339) or second trials (p = 0.0861; n = 8–13 in each group, one-way ANOVA).




