Journal article
Animal Models for Muscular Dystrophy Show Different Patterns of Sarcolemmal Disruption
The Journal of cell biology, Vol.139(2), pp.375-385
10/20/1997
DOI: 10.1083/jcb.139.2.375
PMCID: PMC2139791
PMID: 9334342
Abstract
Genetic defects in a number of components of the dystrophin–glycoprotein complex (DGC) lead to distinct forms of muscular dystrophy. However, little is known about how alterations in the DGC are manifested in the pathophysiology present in dystrophic muscle tissue. One hypothesis is that the DGC protects the sarcolemma from contraction-induced damage. Using tracer molecules, we compared sarcolemmal integrity in animal models for muscular dystrophy and in muscular dystrophy patient samples. Evans blue, a low molecular weight diazo dye, does not cross into skeletal muscle fibers in normal mice. In contrast, mdx mice, a dystrophin-deficient animal model for Duchenne muscular dystrophy, showed significant Evans blue accumulation in skeletal muscle fibers. We also studied Evans blue dispersion in transgenic mice bearing different dystrophin mutations, and we demonstrated that cytoskeletal and sarcolemmal attachment of dystrophin might be a necessary requirement to prevent serious fiber damage. The extent of dye incorporation in transgenic mice correlated with the phenotypic severity of similar dystrophin mutations in humans. We furthermore assessed Evans blue incorporation in skeletal muscle of the dystrophia muscularis (dy/dy) mouse and its milder allelic variant, the dy2J/dy2J mouse, animal models for congenital muscular dystrophy. Surprisingly, these mice, which have defects in the laminin α2-chain, an extracellular ligand of the DGC, showed little Evans blue accumulation in their skeletal muscles. Taken together, these results suggest that the pathogenic mechanisms in congenital muscular dystrophy are different from those in Duchenne muscular dystrophy, although the primary defects originate in two components associated with the same protein complex.
Details
- Title: Subtitle
- Animal Models for Muscular Dystrophy Show Different Patterns of Sarcolemmal Disruption
- Creators
- Volker Straub - Department of Physiology and Biophysics and Department of Neurology, Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City, Iowa 52242; and Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan 48109Jill A Rafael - Department of Physiology and Biophysics and Department of Neurology, Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City, Iowa 52242; and Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan 48109Jeffrey S Chamberlain - Department of Physiology and Biophysics and Department of Neurology, Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City, Iowa 52242; and Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan 48109Kevin P Campbell - Department of Physiology and Biophysics and Department of Neurology, Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City, Iowa 52242; and Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan 48109, Department of Physiology and Biophysics and Department of Neurology, Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City, Iowa 52242; and Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan 48109
- Resource Type
- Journal article
- Publication Details
- The Journal of cell biology, Vol.139(2), pp.375-385
- DOI
- 10.1083/jcb.139.2.375
- PMID
- 9334342
- PMCID
- PMC2139791
- ISSN
- 0021-9525
- eISSN
- 1540-8140
- Language
- English
- Date published
- 10/20/1997
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute
- Record Identifier
- 9984068389702771
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