The phenotype of the
Ant1 −/− mouse includes exercise intolerance, which may reflect an intrinsic increase in skeletal-muscle fatigability, decreased cardiac output due to cardiomyopathy,
6 or both. In the present study, we tested large numbers of fast phases of vestibular nystagmus in an attempt to fatigue the EOMs. Although fast saccadic rates have been reported to engender ocular motor fatigue in myasthenia gravis
15 (a disorder of neuromuscular transmission), the ability of saccades to generate fatigue has never been assessed in ocular motor myopathies, i.e., in disorders more analogous to the defect in the
Ant1 −/− mouse. The
Ant1 mutation did not affect the saccadic rate generated by this protocol. Because absence of fatigue under these in vivo conditions could reflect adaptive changes in motor unit recruitment, we also determined the fatigue resistance of isolated EOMs. Surprisingly,
Ant1 −/− EOMs fatigued at the same rate as control muscles. This finding indicates that absence of
Ant1 did not cause the same metabolic dysfunction in EOMs as occurred in skeletal muscles. However, it should be noted that extraocular muscle has an inherent resistance to fatigue in comparison to skeletal muscle (see Ref.
9 for review), which may explain the absence of EOM fatigue in the
Ant1 −/− mice. Potentially, the increased expression in EOMs of
Ant2, an isoform not typically found in skeletal muscle, is sufficient to functionally compensate for
Ant1 loss. Nevertheless, the
Ant1 −/− EOMs show the morphologic hallmarks of a mitochondrial myopathy, suggesting that upregulation of
Ant2 in EOMs is only partially protective and does not fully suppress abnormal mitochondrial biogenesis.