Tibialis anterior muscles in mdx mice are highly susceptible to contraction-induced injury
Skeletal muscles of patients with Duchenne muscular dystrophy (DMD) and mdx mice lack dystrophin and are more susceptible to contraction-induced injury than control muscles. Our purpose was to develop an assay based on the high susceptibility to injury of limb muscles in mdx mice for use in evaluating therapeutic interventions. The assay involved two stretches of maximally activated tibialis anterior (TA) muscles in situ. Stretches of 40% strain relative to muscle fiber length were initiated from the plateau of isometric contractions. The magnitude of damage was assessed one minute later by the deficit in isometric force. At all ages (2–19 months), force deficits were four- to seven-fold higher for muscles in mdx compared with control mice. For control muscles, force deficits were unrelated to age, whereas force deficits increased dramatically for muscles in mdx mice after 8 months of age. The increase in susceptibility to injury of muscles from older mdx mice did not parallel similar adverse effects on muscle mass or force production. The in situ stretch protocol of TA muscles provides a valuable assay for investigations of the mechanisms of injury in dystrophic muscle and to test therapeutic interventions for reversing DMD.
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- Brooks SV, Zerba E and Faulkner JA (1995) Injury to muscle fibres after single stretches of passive and maximally stimulated muscles in mice. J Physiol (Lond) 488: 459–469.Google Scholar
- Deconinck N, Rafael JA, Beckers-Bleukx G, Kahn D, Deconinck AE, Davies KE and Gillis JM (1998) Consequences of the combined deficiency in dystrophin and utrophin on the mechanical properties and myosin composition of some limb and respiratory muscles of the mouse. Neuromuscul Disord 8: 362–370.PubMedCrossRefGoogle Scholar
- Dubowitz V (1985) Muscle Biopsy: A practical approach. Bailliere Tindall Ltd., London.Google Scholar
- Ebihara S, Guibinga GH, Gilbert R, Nalbantoglu J, Massie B, Karpati G and Petrof BJ (2000) Differential effects of dystrophin and utrophin gene transfer in immunocompetent muscular dystrophy (mdx) mice. Physiol Genom 3: 133–144.Google Scholar
- Emery AEH (1993) Duchenne Muscular Dystrophy. Oxford Medical Publications, Oxford.Google Scholar
- Faulkner JA and Brooks SV (1994) An in situ single skeletal muscle model of contraction-induced injury: mechanistic interpretations. Basic Appl Myol 4: 17–23.Google Scholar
- Faulkner JA, Brooks SV, Dennis RG and Lynch GS (1997) The functional status of dystrophic muscles and functional recovery by skeletal muscles following myoblast transfer. Basic Appl Myol 7: 257–264.Google Scholar
- Greelish JP, Su LT, Lankford EB, Burkman JM, Chen H, Konig SK, Mercier IM, Desjardins PR, Mitchell MA, Zheng XG, Leferovich J, Gao GP, Balice-Gordon RJ, Wilson JM and Stedman HH (1999) Stable restoration of the sarcoglycan complex in dystrophic muscle perfused with histamine and a recombinant adeno-associated viral vector. Nat Med 5: 439–443.PubMedCrossRefGoogle Scholar
- Head SI, Williams DA and Stephenson DG (1992) Abnormalities in structure and function of limb skeletal muscle fibres of dystrophic mdx mice. Proc R Soc Lond B Biol Sci 248: 163–169.Google Scholar
- Matsuda R, Nishikawa A and Tanaka H (1995) Visualization of dystrophic muscle fibers in mdx mouse by vital staining with Evans blue: evidence of apoptosis in dystrophin-deficient muscle. J Biochem (Tokyo) 118: 959–964.Google Scholar
- Mendez J and Keys A (1960) Density and composition of mammalian muscle. Metabolism 9: 184–188.Google Scholar
- Sacco P, Jones DA, Dick JR and Vrbova G (1992) Contractile properties and susceptibility to exercise-induced damage of normal and mdx mouse tibialis anterior muscle. Clin Sci (Colch) 82: 227–236.Google Scholar