Cytoskeletal and mitochondrial pathology in immortalized R349P desmin knock-in myoblasts

Abstract

For a more detailed understanding of desminopathies R349P desmin knock-in mice had previously been generated. Immortalized myoblasts that were derived from the gastrocnemius and soleus muscles of these mice were subjected to a basal characterization in the present study. The morphology, growth rate and differentiation capacity of each myoblast line were examined by light microscopy. Moreover, the desmin intermediate filament network as well as the mitochondrial content and distribution were studied in the myoblasts and differentiated myotubes by applying confocal fluorescence microscopy. Noticeable differences could be observed between homozygous myoblasts and wild-type cells. Due to the mutated desmin, a normal desmin intermediate filament network was not present in homozygous myoblasts. The mitochondria were also affected showing reduced amounts with a lack of mitochondrial networks in the R349P desmin knock-in myoblasts. The here analyzed R349P desmin knock-in myoblasts mirror essential aspects of the pathologies described in murine and human desminopathy muscle tissue and thus can serve as an additional model system to investigate the molecular pathology of desminopathies.