Chevessier F, Schuld J, Orfanos Z, Plank AC, Wolf L, Maerkens A, Unger A, Schlötzer-Schrehardt U, Kley RA, von Hörsten S, Marcus K, Linke WA, Vorgerd M, Van Der Ven PFM, Fuerst DO, Schröder R (2015)
Publication Type: Journal article
Publication year: 2015
Book Volume: 24
Pages Range: 7207-20
Journal Issue: 25
DOI: 10.1093/hmg/ddv421
Filamin C (FLNC) mutations in humans cause myofibrillar myopathy (MFM) and cardiomyopathy, characterized by protein aggregation and myofibrillar degeneration. We generated the first patient-mimicking knock-in mouse harbouring the most common disease-causing filamin C mutation (p.W2710X). These heterozygous mice developed muscle weakness and myofibrillar instability, with formation of filamin C- and Xin-positive lesions streaming between Z-discs. These lesions, which are distinct from the classical MFM protein aggregates by their morphology and filamentous appearance, were greatly increased in number upon acute physical exercise in the mice. This pathology suggests that mutant filamin influences the mechanical stability of myofibrillar Z-discs, explaining the muscle weakness in mice and humans. Re-evaluation of biopsies from MFM-filaminopathy patients with different FLNC mutations revealed a similar, previously unreported lesion pathology, in addition to the classical protein aggregates, and suggested that structures previously interpreted as aggregates may be in part sarcomeric lesions. We postulate that these lesions define preclinical disease stages, preceding the formation of protein aggregates.
APA:
Chevessier, F., Schuld, J., Orfanos, Z., Plank, A.-C., Wolf, L., Maerkens, A.,... Schröder, R. (2015). Myofibrillar instability exacerbated by acute exercise in filaminopathy. Human Molecular Genetics, 24(25), 7207-20. https://doi.org/10.1093/hmg/ddv421
MLA:
Chevessier, Frederic, et al. "Myofibrillar instability exacerbated by acute exercise in filaminopathy." Human Molecular Genetics 24.25 (2015): 7207-20.
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