Figure 3.

scAAV9-miDnm1a Treatment Improves Developmental Outcomes

(A) Treatment significantly improved the grip strength at PND 11 of Dnm1^Ftfl/Ftfl mice (n = 30) compared to control-injected (n = 28) mice (p = 0.0009, least-squares regression using rank- and normal-quantile transformed data), with no effect of litter size, sex, or virus dose. Treated Dnm1^Ftfl/Ftfl mice did not differ from treated (n = 24) or control-injected (n = 19) Dnm1^+/+ mice (same test as above with Tukey’s HSD post hoc test, p > 0.05). (B and C) In an assay for sensorimotor development, at PND 9 and PND 11, control-injected Dnm1^Ftfl/Ftfl mice had a higher latency, albeit not significant for the easier 90° turn (B) (p > 0.05, least-squares regression using rank- and normal-quantile transformed data, Dunnett’s post hoc test). However, for the more difficult 180° turn (C), control-injected Dnm1^Ftfl/Ftfl mice showed a significantly higher latency at PND 11 compared to the other three groups (p < 0.001, Dunnett’s post hoc test). (D) Control-injected Dnm1^Ftfl/Ftfl mice (n = 24) show severe ataxia; importantly, treatment with miDnm1a (n = 17) eliminates this phenotype (p = 6.9 × 10⁻¹⁷, log-Poisson test) and restores Dnm1^Ftfl/Ftfl motor coordination back to the level of treated (n = 16) and control-injected (n = 23) Dnm1^+/+ mice (p = 0.19 mixed model log-Poisson test). (E and F) Using locomotion (E) and velocity (F) as a proxy for possible hyperactivity, we observed that there was no significant difference between all groups (p > 0.05, one-way ANOVA). ^∗p < 0.01; ^∗∗p < 0.001; ^∗∗∗∗p < 0.00001.