Preaged remodeling of myofibrillar cytoarchitecture in skeletal muscle expressing R349P mutant desmin

Diermeier S, Buttgereit A, Schürmann S, Winter L, Xu H, Murphy RM, Clemen CS, Schröder R, Friedrich O (2017)

Publication Type: Journal article

Publication year: 2017

Journal

Neurobiology of Aging Elsevier

Book Volume: 58

Pages Range: 77-87

DOI: 10.1016/j.neurobiolaging.2017.06.001

Abstract

The majority of hereditary and acquired myopathies are clinically characterized by progressive muscle weakness. We hypothesized that ongoing derangement of skeletal muscle cytoarchitecture at the single fiber level may precede and be responsible for the progressive muscle weakness. Here, we analyzed the effects of aging in wild-type (wt) and heterozygous (het) and homozygous (hom) R349P desmin knock-in mice. The latter harbor the ortholog of the most frequently encountered human R350P desmin missense mutation. We quantitatively analyzed the subcellular cytoarchitecture of fast- and slow-twitch muscles from young, intermediate, and aged wt as well as desminopathy mice. We recorded multiphoton second harmonic generation and nuclear fluorescence signals in single muscle fibers to compare aging-related effects in all genotypes. The analysis of wt mice revealed that the myofibrillar cytoarchitecture remained stable with aging in fast-twitch muscles, whereas slow-twitch muscle fibers displayed structural derangements during aging. In contrast, the myofibrillar cytoarchitecture and nuclear density were severely compromised in fast- and slow-twitch muscle fibers of hom R349P desmin mice at all ages. Het mice only showed a clear degradation in their fiber structure in fast-twitch muscles from the adult to the presenescent age bin. Our study documents distinct signs of normal and R349P mutant desmin-related remodeling of the 3D myofibrillar architecture during aging, which provides a structural basis for the progressive muscle weakness.

Authors with CRIS profile

Stefanie Nübler Lehrstuhl für Medizinische Biotechnologie Andreas Buttgereit Lehrstuhl für Medizinische Biotechnologie Sebastian Schürmann Lehrstuhl für Medizinische Biotechnologie Rolf Schröder Professur für Neuropathologie Oliver Friedrich Lehrstuhl für Medizinische Biotechnologie

Additional Organisation(s)

Muscle Research Center Erlangen (MURCE)

Related research project(s)

Progressive Muscle Dysfunction resulting from chronic Remodeling of Cellular Architecture in inherited Muscle Diseases Advanced Second Harmonic Generation - Microscopy and quantitative Morphometry in skeletal Muscles from Animal Models of Duchenne Muscular Dystrophy and Desminopathy Nov. 1, 2013 - Aug. 30, 2018 Advanced Optical Laser Technologies for Life Sciences and personalized Medicine (ADVENDO-LIFE) (ADVENDO-LIFE) Jan. 1, 2014 - Dec. 31, 2015

Involved external institutions

Universität zu Köln DE Germany (DE) La Trobe University AU Australia (AU)

How to cite

APA:

Diermeier, S., Buttgereit, A., Schürmann, S., Winter, L., Xu, H., Murphy, R.M.,... Friedrich, O. (2017). Preaged remodeling of myofibrillar cytoarchitecture in skeletal muscle expressing R349P mutant desmin. Neurobiology of Aging, 58, 77-87. https://doi.org/10.1016/j.neurobiolaging.2017.06.001

MLA:

Diermeier, Stefanie, et al. "Preaged remodeling of myofibrillar cytoarchitecture in skeletal muscle expressing R349P mutant desmin." Neurobiology of Aging 58 (2017): 77-87.

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