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

Ritter P, Nübler S, Buttgereit A, Smith LR, Mühlberg A, Bauer J, Michael M, Kreiß L, Haug M, Barton E, Friedrich O (2022)

Publication Type: Journal article, Original article

Publication year: 2022

Journal

Book Volume: 23

Journal Issue: 18

DOI: 10.3390/ijms231810841

Abstract

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.

Authors with CRIS profile

Involved external institutions

University of California Davis (UCDAVIS) United States (USA) (US) University of Florida United States (USA) (US)

How to cite

APA:

Ritter, P., Nübler, S., Buttgereit, A., Smith, L.R., Mühlberg, A., Bauer, J.,... Friedrich, O. (2022). Myofibrillar Lattice Remodeling Is a Structural Cytoskeletal Predictor of Diaphragm Muscle Weakness in a Fibrotic mdx (mdx Cmah(-/-)) Model. International Journal of Molecular Sciences, 23(18). https://doi.org/10.3390/ijms231810841

MLA:

Ritter, Paul, et al. "Myofibrillar Lattice Remodeling Is a Structural Cytoskeletal Predictor of Diaphragm Muscle Weakness in a Fibrotic mdx (mdx Cmah(-/-)) Model." International Journal of Molecular Sciences 23.18 (2022).

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