Desmin‐related myopathies in mice and man

Abstract

Desmin, the main intermediate filament (IF) protein in skeletal and heart muscle cells, is of great importance as a part of the cytoskeleton. The IFs surround and interlink myofibrils, and connect the peripheral myofibrils with the sarcolemma. In myotendinous junctions and neuromuscular junctions of skeletal muscle fibres, desmin is enriched. In the heart, desmin is increased at intercalated discs, the attachment between cardiomyocytes, and it is the main component in Purkinje fibres of the conduction system. Desmin is the first muscle-specific protein to appear during myogenesis. Nevertheless, lack of desmin, as shown from experiments with desmin knockout (K/O) mice, does not influence myogenesis or myofibrillogenesis. However, the desmin knock-out mice postnatally develop a cardiomyopathy and a muscle dystrophy in highly used skeletal muscles. In other skeletal muscles the organization of myofibrils is remarkably unaffected. Thus, the main consequence of the lack of desmin is that the muscle fibres become more susceptible to damage. The loss of membrane integrity leads to a dystrophic process, with degeneration and fibrosis. In the heart cardiac failure develops, whereas in affected skeletal muscles regenerative attempts are seen. In humans, accumulations of desmin have been a hallmark for presumptive desmin myopathies. Recent investigations have shown that some families with such a myopathy have a defect in the gene coding for alphaB-crystallin, whereas others have mutations in the desmin gene. Typical features of these patients are cardiac affections and muscle weakness. Thus, mutations in the desmin gene is pathogenic for a distinct type of muscle disorder.

Progenitor Cell Isolation from Muscle-derived Cells based on Adhesion Properties

“…Medium was changed every 2 days. To select the clonally derived colonies of myogenic nature from those developed from fibroblastic cell, all cultures were fixed in 4% cold PFA at day 11 and initially tested for their expression of desmin, a myogenic lineage-restricted intermediate filament protein (Carlsson and Thornell 2001). Desmin was detected with mouse MAb (1:50; Dako), in the same way as described above.…”

Desmin: molecular interactions and putative functions of the muscle intermediate filament protein

“…It is the first muscle-specific structural protein and one of the more persistent in several differentiation conditions. The recent finding of several cases of human diseases linked to altered desmin expression (8) has renewed the interest in the physiological roles of desmin. However, despite all the curiosity it inspired, the function of desmin is still unknown.…”

Abnormal Accumulation of Desmin in Gastrocnemius Myofibers of Patients with Peripheral Artery Disease

“…1; Capetanaki et al 2007;Goldfarb et al 2004). Desmin IFs bundle myofibrils such that they are aligned at the Z-discs (Capetanaki et al 2007;Dalakas et al 2000) and set neighboring myofibers into alignment at their Z-discs (Capetanaki et al 1997;Carlsson and Thornell 2001;Lazarides 1980), thereby facilitating translation of sarcomeric contraction into muscle contraction (Bloch and Gonzalez-Serratos 2003;Capetanaki et al 2007;Carlsson and Thornell 2001;Goldfarb et al 2004;Paulin et al 2004). This same system of IFs provides structure to the mitochondrial network (Capetanaki et al 1997;Milner et al 2000).…”