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Muscular Dystrophy in mdx Mice Despite Lack of Neuronal Nitric Oxide Synthase
Author(s) -
Chao Daniel S.,
Silvagno Francesca,
Bredt David S.
Publication year - 1998
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1998.71020784.x
Subject(s) - dystrophin , duchenne muscular dystrophy , muscular dystrophy , mdx mouse , nitric oxide synthase , utrophin , cytosol , skeletal muscle , endocrinology , medicine , sarcolemma , nitric oxide , biology , itga7 , chemistry , microbiology and biotechnology , biochemistry , enzyme
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.