Figure 4.

Restoration of α-DG glycosylation and improvement of cardiac contractile capacity by delivery of adeno-associated virus (AAV)9 encoding fukutin-related protein (FKRP) gene. The AAV9-syn100-FKRP and AAV9-CB-FKRP vectors (3 × 10¹¹ vg/pup) were delivered into the neonatal mice, and age matched heterozygous and homozygous mice were used as controls. Gene expression and heart function examinations were performed 7 months after vector delivery. (a) Overexpression of FKRP via AAV vector, driven by muscle-specific syn100 promoter or ubiquitous CB promoter, all restored the glycosylation of α-DG in the homozygous FKRP L276I^KI mice shown by the IF staining. (b) The western blot further indicated that overexpression of FKRP in homozygous mice completely restored the glycosylation of α-DG. For the western blot of FKRP expression, homozygous mice were treated by AAV9-CB-FKRP vector. (c) The dobutamine stress Echo indicated improvement in ejection fraction (EF) for both syn100-FKRP and CB-FKRP treated groups after dobutamine stimulation. (d) The dobutamine stress Echo displayed enhanced cardiac contractile function in fractional shortening (FS) for both syn100-FKRP- and CB-FKRP-treated groups after dobutamine stimulation. (*P < 0.05, n = 3 for treated group, and n = 8 for hetero and homo groups for both c and d).