Sparing of the extraocular muscles in mdx mice with absent or reduced utrophin expression: A life span analysis

• Eye muscles are spared in muscular dystrophy models in the absence of dystrophin and utrophin.
• Pax7- and MyoD-positive cells were retained and were similar to age-matched wild type controls.
• Thus, utrophin is not involved in extraocular muscle sparing in these genotypes.

Sparing of the extraocular muscles in muscular dystrophy is controversial. To address the potential role of utrophin in this sparing, mdx:utrophin+/− and mdx:utrophin−/− mice were examined for changes in myofiber size, central nucleation, and Pax7-positive and MyoD-positive cell density at intervals over their life span. Known to be spared in the mdx mouse, and contrary to previous reports, the extraocular muscles from both the mdx:utrophin+/− and mdx:utrophin−/− mice were also morphologically spared. In the mdx:utrophin+/− mice, which have a normal life span compared to the mdx:utrophin−/− mice, the myofibers were larger at 3 and 12 months than the wild type age-matched eye muscles. While there was a significant increase in central nucleation in the extraocular muscles from all mdx:utrophin+/− mice, the levels were still very low compared to age-matched limb skeletal muscles. Pax7- and MyoD-positive myogenic precursor cell populations were retained and were similar to age-matched wild type controls. These results support the hypothesis that utrophin is not involved in extraocular muscle sparing in these genotypes. In addition, it appears that these muscles retain the myogenic precursors that would allow them to maintain their regenerative capacity and normal morphology over a lifetime even in these more severe models of muscular dystrophy.