Figure 4.

I.c.v. delivery of high-dose AAV9-IGHMBP2 improved the NMJ pathology of FVB-nmd mice at early and late time points

(A) Representative images of NMJs from gastrocnemius muscles of high-dose P2- and P8-treated mice (n = 4) at P42 compared to those of age-matched WT mice (n = 3), while the NMJ of untreated FVB-nmd mice (n = 4) at P14 was analyzed in comparison to the age-matched unaffected HET (n = 3). Muscles were labeled with α-bungarotoxin (α-BTX) for acetylcholine receptors (AChRs), anti-neurofilament, and anti-synaptic vesicle protein 2 (SV2) for nerve terminals. Fluorescent images were taken at 40× magnification. (B) Percentage of fully innervated, partially denervated, and fully denervated muscles. Percentage of fully innervated in FVB-nmd mice was less than 40%, compared to 90% in HET counterparts (two-way ANOVA, p < 0.0001). P2-treated NMJs were ~85% fully innervated and ~10% fully denervated versus 95% and 5% in WT cohort (two-way ANOVA, p > 0.5). P8-treated mice exhibited ~65% full innervation (two-way ANOVA, P8-treated versus P2-treated and WT, p < 0.0001) and ~22% full denervation (two-way ANOVA, P8- versus P2-treated, p < 0.05; P8 versus WT, p < 0.01). Scale bar, 50 μm. Error bars represent mean ± SEM. ∗p < 0.05, ∗∗p < 0.01, and ∗∗∗∗p < 0.0001.