Myofibrillar Lattice Remodeling Is a Structural Cytoskeletal Predictor of Diaphragm Muscle Weakness in a Fibrotic mdx (mdx Cmah −/−) Model.

Autor: Ritter, Paul, Nübler, Stefanie, Buttgereit, Andreas, Smith, Lucas R., Mühlberg, Alexander, Bauer, Julian, Michael, Mena, Kreiß, Lucas, Haug, Michael, Barton, Elisabeth, Friedrich, Oliver
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Zdroj: International Journal of Molecular Sciences; Sep2022, Vol. 23 Issue 18, pN.PAG-N.PAG, 12p
Abstrakt: Duchenne muscular dystrophy (DMD) is a degenerative genetic myopathy characterized by complete absence of dystrophin. Although the mdx mouse lacks dystrophin, its phenotype is milder compared to DMD patients. The incorporation of a null mutation in the Cmah gene led to a more DMD-like phenotype (i.e., more fibrosis). Although fibrosis is thought to be the major determinant of 'structural weakness', intracellular remodeling of myofibrillar geometry was shown to be a major cellular determinant thereof. To dissect the respective contribution to muscle weakness, we assessed biomechanics and extra- and intracellular architecture of whole muscle and single fibers from extensor digitorum longus (EDL) and diaphragm. Despite increased collagen contents in both muscles, passive stiffness in mdx Cmah − / − diaphragm was similar to wt mice (EDL muscles were twice as stiff). Isometric twitch and tetanic stresses were 50% reduced in mdx Cmah − / − diaphragm (15% in EDL). Myofibrillar architecture was severely compromised in mdx Cmah − / − single fibers of both muscle types, but more pronounced in diaphragm. Our results show that the mdx Cmah − / − genotype reproduces DMD-like fibrosis but is not associated with changes in passive visco-elastic muscle stiffness. Furthermore, detriments in active isometric force are compatible with the pronounced myofibrillar disarray of the dystrophic background. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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