Mechanics of dystrophin deficient skeletal muscles in very young mice and effects of age

• Published in: American Journal of Physiology: Cell Physiology Vol. 321; no. 2; pp. C230 - C246
• Main Authors: Lopez, Michael A, Bontiff, Sherina, Adeyeye, Mary, Shaibani, Aziz I, Alexander, Matthew S, Wynd, Shari, Boriek, Aladin M
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.08.2021
• Subjects: Age; Animal models; Animals; Compliance; Cytoskeleton; Diaphragm; Disease Models, Animal; Duchenne's muscular dystrophy; Dystrophin; Dystrophin - deficiency; Fibrosis; Isometric Contraction - physiology; Mechanical properties; Mechanics; Mice, Transgenic; Muscle contraction; Muscle Contraction - physiology; Muscle Fibers, Skeletal - metabolism; Muscle, Skeletal - metabolism; Muscular Dystrophy, Duchenne - metabolism; Muscular Dystrophy, Duchenne - physiopathology; Rodents; Skeletal muscle; Viscoelasticity; respiratory muscle mechanics; MDX muscle pathology; muscle weakness
• ISSN: 0363-6143; 1522-1563
• DOI: 10.1152/ajpcell.00155.2019

The MDX mouse is an animal model of Duchenne muscular dystrophy, a human disease marked by an absence of the cytoskeletal protein, dystrophin. We hypothesized that ) dystrophin serves a complex mechanical role in skeletal muscles by contributing to passive compliance, viscoelastic properties, and contractile force production and ) age is a modulator of passive mechanics of skeletal muscles of the MDX mouse. Using an in vitro biaxial mechanical testing apparatus, we measured passive length-tension relationships in the muscle fiber direction as well as transverse to the fibers, viscoelastic stress-relaxation curves, and isometric contractile properties. To avoid confounding secondary effects of muscle necrosis, inflammation, and fibrosis, we used very young 3-wk-old mice whose muscles reflected the prefibrotic and prenecrotic state. Compared with controls, ) muscle extensibility and compliance were greater in both along fiber direction and transverse to fiber direction in MDX mice and ) the relaxed elastic modulus was greater in dystrophin-deficient diaphragms. Furthermore, isometric contractile muscle stress was reduced in the presence and absence of transverse fiber passive stress. We also examined the effect of age on the diaphragm length-tension relationships and found that diaphragm muscles from 9-mo-old MDX mice were significantly less compliant and less extensible than those of muscles from very young MDX mice. Our data suggest that the age of the MDX mouse is a determinant of the passive mechanics of the diaphragm; in the prefibrotic/prenecrotic stage, muscle extensibility and compliance, as well as viscoelasticity, and muscle contractility are altered by loss of dystrophin.