Figure 5. DNM2 reduction rescues skeletal muscle histology and improves contractility in extensor digitorum longus muscles of Speg-rescue mice.

(A) Representative TA muscle images of control, Speg-KO, and Speg-rescue mice at 3 months of age. (B) H&E stains of TA muscles from control, Speg-KO, and Speg-rescue mice at 3 months of age. Scale bar: 100 μm. (C) Distribution of the cross-sectional area (CSA) in control, Speg-KO, and Speg-rescue TA muscles (n = 4 per group). (D) The mean CSA of Speg-rescue TA muscles is significantly larger than that of Speg-KO (****P < 0.0001, over 500 fibers were analyzed from each group; 1-way ANOVA with Tukey’s post hoc test). (E) Absolute peak tetanic force was significantly reduced in EDL muscles from Speg-KO mice compared with muscles from control animals. Muscles from the Speg-rescue mice were not different from either of the other groups. (F) Peak tetanic force expressed relative to EDL physiological CSA. Peak force/CSA was significantly reduced in Speg-KO animals (compared with control) but was restored to control levels in the Speg-rescue group. (G) Force-frequency relationships of EDL muscles. Forces obtained at different frequencies of stimulation were expressed relative to peak force and fit by the equation P_min + ([P_max – P_min]/[1+([K/Hz]^H)]), where P_min is the minimum force, P_max is the maximum force, K is the frequency corresponding to the inflection point of the curve, and H is a unitless parameter defining the curve’s slope. (H) The parameter K was significantly greater for the Speg-KO and the Speg-rescue EDL muscles compared with control, indicating a significant shift of the Speg-KO curve to the right. The parameter H did not differ between control (4.05 ± 0.21), Speg-KO (3.74 ± 0.04), and Speg-rescue (4.32 ± 0.22) muscles. *P ˂ 0.05; **P ˂ 0.01; ***P ˂ 0.001, n = 5 per genotype; 1-way ANOVA with Tukey’s post hoc test.