Mouse models of dominant ACTA1 disease recapitulate human disease and provide insight into therapies
Ravenscroft G, Jackaman C, Bringans S, Papadimitriou JM, Griffiths LM, McNamara E, Bakker AJ,...
Expression of cardiac a-actin spares extraocular muscles in skeletal muscle a-actin diseases – Quantification of striated a-actins by MRM-mass spectrometry
Ravenscroft G., Colley S., Walker K., Clement S., Bringans S.D., Lipscombe R.J., Fabian V., Laing N., and Nowak K.J. (2008) Neuromuscular Disorders,18:953-958.
Abstract
As with many skeletal muscle diseases, the extraocular muscles (EOMs) are spared in skeletal muscle a-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 a-actin, the a-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 a-actin in the extraocular muscles of human, pig and sheep to those in the heart. The sparing of extraocular muscles in skeletal muscle a-actin disease is thus probably due to greater levels of cardiac a-actin, than the negligible amounts in skeletal muscles, diluting out the effects of the mutant skeletal muscle a-actin.