Figure 3.

AAV transduction and FXN expression in the FXN-MCK mouse model

(A and B) VCN per group in mouse heart samples at 4 weeks postdosing (A) and 12 weeks postdosing (B). (C and D) FXN protein expression per group in mouse heart samples at 4 weeks postdosing (C) and 12 weeks postdosing (D). (B and D) All of the animals in cohort 2 survived until 18 WOA, except vehicle-treated FXN-MCK mice, which were terminated at 10 WOA due to mortality phenotype. Data are mean ± SD, where columns represent means, error bars represent SDs, and each point represents an individual animal; data were analyzed by mixed-effects analysis 1-way ANOVA of Tukey multiple comparisons test. (E) Representative western blot demonstrated a protein band at the same size as the rhFXN detected in heart tissue protein samples from FXN-MCK mice receiving AAV-hFXN at 1E+14 vg/kg at 4 weeks postdosing and 12 weeks postdosing. (F) Associated with FXN deficiency, FXN-MCK mice have a downregulation of immunoreactive levels of complexes I and II compared with WT. Expression of AAV FXN restores complex I and II levels to near normal. ∗p < 0.05; ∗∗p < 0.01. ND, nondetectable; ns, not significant.