A common gene deletion or mutation of
delta-sarcoglycan (delta-SG) in
dystrophin-related
proteins (DRPs) is identified in both TO-2 strain hamsters and human families with
dilated cardiomyopathy. We have succeeded in the long-lasting in vivo supplementation of a normal delta-SG gene by recombinant adeno-associated virus vector, restoration of the morphological and functional degeneration, and improvement in the prognosis of the TO-2 hamster. To evaluate the integrity of the sarcolemma (SL) and the subsequent change of organelles in cardiomyocytes of the TO-2 strain hamster, we examined electron microscopy (EM) images focusing on the sarcolemmal stability at the end stage of
heart failure. Two types of sarcolemmal degradation were detected: the widened and locally thickened SL, and blurred and discontinuous SL. Bizarrely formed mitochondria of varying sizes were also observed. Immuno-EM revealed clear expression of
dystrophin in the SL and intense expression at the costamere as well as at the T-tubules in the control F1B strain hearts, but a patchy deposition of
dystrophin was observed along the SL without the transgene of delta-SG. In contrast to the previous reports that
dystrophin's integrity was intact, the present results suggest that the gene deletion of delta-SG and the loss of delta-SG
protein in the SL cardioselectively cause the morphological and functional deterioration of
dystrophin and the resultant instability of the SL. The sarcolemmal fragility may be similar to
Duchenne-type progressive muscular dystrophy in skeletal muscle. In addition to the mechanical role, another aspect of DRPs for the intracellular signal transmission is also discussed.