FIG. 4.

AAV-mediated ΔR4/ΔC microdystrophin expression protected young (7 weeks old at infection) EDL muscles from eccentric contraction-induced injury. The left EDL muscles of 7-week-old mdx mice were infected with AV.ΔR4/ΔC. The contralateral right EDL muscles were infected with AV.RSV.AP. Viral transduction and muscle physiology were examined when mice were 5 months of age. (A) Representative photomicrographs of immunofluorescence staining with the N-terminal-specific (for ΔR4/ΔC microdystrophin, left) and the C-terminal-specific (for endogenous revertant murine dystrophin, right) antibodies. Nuclei were stained with DAPI. Scale bar, 300 μm. On average, approximately 58% of EDL myofibers were transduced by AAV (Table 2). Revertant myofibers were occasionally seen with the antibody against the dystrophin C-terminus (arrow, right). (B) Effect of partial microdystrophin transduction on specific tetanic force in the mdx EDL muscle. Open bar, EDL muscles infected with AV.RSV.AP; filled bar, EDL muscles infected with AV.ΔR4/ΔC. N = 5 pairs. *The difference between AV.ΔR4/ΔC- and AV.RSV.AP-infected muscles was statistically significant ( P < 0.05). (C) Partial microdystrophin expression protected the EDL muscle from the majority of eccentric contraction-induced injuries (from the third to the ninth cycle). Open circle, EDL muscles infected with AV.RSV.AP (mean − SEM); closed circle, EDL muscles infected with AV.ΔR4/ΔC (mean + SEM). N = 5 pairs. *The difference between AV.ΔR4/ΔC- and AV.RSV.AP-infected muscles was statistically significant ( P < 0.05).