Expression of cardiac α-actin spares extraocular muscles in skeletal muscle α-actin diseases – Quantification of striated α-actins by MRM-mass spectrometry

Abstract As with many skeletal muscle diseases, the extraocular muscles (EOMs) are spared in skeletal muscle α-actin diseases, with no ophthalmoplegia even in severely affected patients. We hypothesised that the extraocular muscles sparing in these patients was due to significant expression of cardiac α-actin, the α-actin isoform expressed in heart and foetal skeletal muscle. We have shown by immunochemistry, Western blotting and a novel MRM-mass spectrometry technique, comparable levels of cardiac α-actin in the extraocular muscles of human, pig and sheep to those in the heart. The sparing of extraocular muscles in skeletal muscle α-actin disease is thus probably due to greater levels of cardiac α-actin, than the negligible amounts in skeletal muscles, diluting out the effects of the mutant skeletal muscle α-actin.