Journal article
mdx Muscle pathology is independent of nNOS perturbation
Human molecular genetics, Vol.7(5), pp.823-829
1998
DOI: 10.1093/hmg/7.5.823
PMID: 9536086
Abstract
In skeletal muscle, neuronal nitric oxide synthase (nNOS) is anchored to the sarcolemma via the dystrophin-glycoprotein complex. When dystrophin is absent, as in Duchenne muscular dystrophy patients and in mdx mice, nNOS is mislocalized to the interior of the muscle fiber where it continues to produce nitric oxide. This has led to the hypothesis that free radical toxicity from mislocalized nNOS may contribute to mdx muscle pathology. To test this hypothesis directly, we generated mice devoid of both nNOS and dystrophin. Overall, the nNOS-dystrophin null mice maintained the dystrophic characteristics of mdx mice. We evaluated the mice for several features of the dystrophic phenotype, including membrane damage and muscle morphology. Removal of nNOS did not alter the extent of sarcolemma damage, which is a hallmark of the dystrophic phenotype. Furthermore, muscle from nNOS-dystrophin null mice maintain the histological features of mdx pathology. Our results demonstrate that relocalization of nNOS to the cytosol does not contribute significantly to mdx pathogenesis.
Details
- Title: Subtitle
- mdx Muscle pathology is independent of nNOS perturbation
- Creators
- R. H CROSBIE - Howard Hughes Medical Institute, Department of Physiology and Biophysics, Department of Neurology, University of Iowa College of Medicine, Iowa City, IA 52242, United StatesV STRAUB - Howard Hughes Medical Institute, Department of Physiology and Biophysics, Department of Neurology, University of Iowa College of Medicine, Iowa City, IA 52242, United StatesH.-Y YUN - Departments of Neurology and Neuroscience, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287, United StatesJ. C LEE - Howard Hughes Medical Institute, Department of Physiology and Biophysics, Department of Neurology, University of Iowa College of Medicine, Iowa City, IA 52242, United StatesJ. A RAFAEL - Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, United StatesJ. S CHAMBERLAIN - Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, United StatesV. L DAWSON - Departments of Neurology and Neuroscience, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287, United StatesT. M DAWSON - Departments of Neurology and Neuroscience, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287, United StatesK. P CAMPBELL - Howard Hughes Medical Institute, Department of Physiology and Biophysics, Department of Neurology, University of Iowa College of Medicine, Iowa City, IA 52242, United States
- Resource Type
- Journal article
- Publication Details
- Human molecular genetics, Vol.7(5), pp.823-829
- Publisher
- Oxford University Press; Oxford
- DOI
- 10.1093/hmg/7.5.823
- PMID
- 9536086
- ISSN
- 0964-6906
- eISSN
- 1460-2083
- Language
- English
- Date published
- 1998
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Obstetrics and Gynecology
- Record Identifier
- 9984068274502771
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