Muscular dystrophy in mdx mice despite lack of neuronal nitric oxide synthase.
Neuronal nitric oxide synthase (nNOS) is a component of the dystrophin complex in skeletal muscle. The absence of dystrophin protein in Duchenne muscular dystrophy and in mdx mouse causes a redistribution of nNOS from the plasma membrane to the cytosol in muscle cells. Aberrant nNOS activity in the cytosol can induce free radical oxidation, which is toxic to myofibers. To test the hypothesis that derangements in nNOS disposition mediate muscle damage in Duchenne dystrophy, we bred dystrophin-deficient mdx male mice and female mdx heterozygote mice that lack nNOS. We found that genetic deletion of nNOS does not itself cause detectable pathology and that removal of nNOS does not influence the extent of increased sarcolemmal permeability in dystrophin-deficient mice. Thus, histological analyses of nNOS-dystrophin double mutants show pathological changes similar to the dystrophin mutation alone. Taken together, nNOS defects alone do not produce muscular dystrophy in the mdx model.
Department of Physiology, University of California at San Francisco, USA.
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Chao
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Silvagno
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Bredt
D000818:Animals; D002463:Cell Membrane Permeability / Q000502:physiology; D005260:Female; D008297:Male; D051379:Mice; D018101:Mice, Inbred mdx / Q000502:physiology*; D018345:Mice, Knockout / Q000502:physiology*; D018482:Muscle, Skeletal / Q000201:enzymology / Q000473:pathology; D009137:Muscular Dystrophy, Animal / Q000378:metabolism* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000201:enzymology*; D019001:Nitric Oxide Synthase / Q000235:genetics* / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D010375:Pedigree; D012508:Sarcolemma / Q000201:enzymology
D009419:Nerve Tissue Proteins; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse