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Molecular and cellular contractile dysfunction of dystrophic muscle from young mice
Author(s) -
Lowe Dawn A.,
Williams Brian O.,
Thomas David D.,
Grange Robert W.
Publication year - 2006
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.20562
Subject(s) - dystrophin , contractility , myosin , medicine , duchenne muscular dystrophy , endocrinology , utrophin , muscle contraction , contraction (grammar) , extensor digitorum longus muscle , muscular dystrophy , mdx mouse , chemistry , biology , anatomy , skeletal muscle , microbiology and biotechnology
The purpose of this study was to determine whether contractile protein alterations are responsible for force deficits in young dystrophic muscle. Contractility of intact extensor digitorum longus muscles and permeabilized fibers from wild‐type (wt), dystrophin‐deficient ( mdx ), and dystrophin/utrophin‐deficient ( mdx:utrn −/− ) mice aged 21 and 35 days was determined. Myosin structural dynamics were assessed by site‐directed spin labeling and electron paramagnetic resonance spectroscopy. The principal finding was that force generation was depressed by ∼20% in mdx muscles, but fiber Ca 2+ ‐activated force and myosin structure were not different from wt animals, suggesting that contractile proteins are not responsible for the force deficits in those muscles. For mdx:utrn −/− mice, muscle and fiber forces were ∼40% lower than wt and the fraction of strong‐binding myosin during contraction was reduced by 13%. These data indicate that contractile protein alterations, in addition to myosin dysfunction, cause force deficit in muscles from young mdx:utrn −/− mice. Elucidating the molecular mechanisms underlying muscle weakness at the onset of disease is important for designing treatment strategies. Muscle Nerve, 2006