Figure 2.

Analysis of functional outcomes in R75W/Gjb1-null and N175D/Gjb1-null mice injected pre-onset with AAV9-Mpz.GJB1 compared to AAV9-Mpz.Egfp (mock)

Diagram showing the pre-onset treatment trial design with timing of functional and morphological analysis (A). Results of foot grip analysis of R75W/Gjb1-null (B–F) and N175D/Gjb1-null mice (G–K) comparing AAV9-Mpz.GJB1-treated (GJB1) and mock-treated mice, as indicated. While there were no differences between the treatment groups before the injection (B and G), 2 months post-injection grip strength improved in treated mice of both genotypes compared to the mock groups (C and H). Improved performance continued at 4 months post injection (6 months old) (D and I) as well as at 6 months post injection (8 months of age) in treated mice of both mutant lines compared to mock groups (E and J). Longitudinal analysis within each group showed improved motor performance over time in treated R75W/Gjb1-null and N175D/Gjb1-null mutants while mock groups either remained stable or decreased (F and K). Sciatic nerve motor conduction velocity (MNCV) also showed significant improvement 6 months after treatment compared to the mock groups in both R75W/Gjb1-null-treated (L) and N175D/Gjb1-null-treated (N) mice. The amplitude of the compound muscle action potential (CMAP) was also evaluated in both genotypes with no differences observed between treated and mock groups (M and O). Values represent mean±SEM. Statistical analysis was performed using Mann-Whitney test (B–E, G–J, and L–O) or one-way ANOVA (F and K).