Figure 4.

Muscle fiber size increase in CAPN3 KO mice with AAV.CAPN3 gene therapy

(A) SDH staining showing muscle fiber types in TA muscle based on mitochondrial content: fatigue-resistant slow-twitch oxidative (STO; dark) or type1 fibers, fast-twitch oxidative (FTO; intermediate) fibers with intermediate staining intensity, and fast-twitch glycolytic (FTG; light) fibers with the lightest staining intensity. (B) Representative images from TA muscle showing three different zones (deep, intermediate, and superficial; designated zones 1, 2, and 3) from the UT, LD (3 × 10¹² vg), and HD (6 × 10¹² vg) treatment cohorts. (C) Fiber size measurements, done on images derived from 3 zones of TA muscle, showed significant increases for all fiber types (STO, FTO, and FTG) in the LD and HD cohorts compared with the UT CAPN3 KO group. Each bar represents the mean ± SEM of 12–15 mice in each group. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗∗p < 0.0001 (compared with UT), two-way ANOVA, Tukey’s multiple comparisons test. Scale bar, 30 μm in the UT zone (applies to all).