Intranuclear rod myopathy: molecular pathogenesis and mechanisms of weakness

Abstract

Data from our tissue culture and Drosophila models show that the Val163Met mutation in alpha-skeletal actin can affect the dynamics of other actin isoforms and severely disrupt sarcomeric structure, processes that can contribute to muscle weakness. However, in human muscle, there is evidence of regeneration, and the mutant protein tends to aggregate rather than incorporate into cytoplasmic microfilaments in cells. These are likely compensatory processes that ameliorate the effects of the mutant actin and contribute to the milder clinical and pathological disease phenotype.