Activated satellite cells are present in uninjured extraocular muscles of mature mice

Purpose: We recently demonstrated that there is a continuous process of myonuclear addition into normal, uninjured adult myofibers in rabbit extraocular muscles (EOM). This phenomenon is not seen in skeletal muscles from normal, adult limbs. These features may explain the selective involvement of the EOM in progressive external ophthalmoplegia and oculopharyngeal muscular dystrophy due to an accumulation of damaged DNA in mitochondria and nuclei within the EOM as a result of repeated cycling of the muscle satellite cells. Many testable hypotheses flow from these observations. We investigated whether continuous myonuclear addition is present in normal mouse EOM so that mouse models of genetic disorders can be used to study the pathogenic mechanisms and to test potential therapies for human muscle disorders. Methods: Bromodeoxyuridine (brdU) was injected intraperitoneally into C57 adult mice every 2 hours for 12 hours. Twenty-four hours later the animals were sacrificed, and the globes with the muscles attached were prepared for immunohistochemical localization of brdU-positive nuclei within the EOM. All cross sections were immunostained for both brdU and either dystrophin or laminin. Results: All the rectus muscles from the mouse EOM examined contained both satellite cells and myonuclei that were positive for brdU. This demonstrates the division of satellite cells and the fusion of their daughter cells with existing adult EOM myofibers in mice. Conclusions: These data indicate that the process of continuous myonuclear addition is also active in mouse EOM. These findings will allow various mutant mouse models to be used to study the pathogenesis and treatment of various muscle disorders. The existence of continuous myonuclear addition in adult, uninjured EOM fundamentally changes the accepted notion that EOM myofibers are postmitotic.