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Animal models for muscular dystrophy show different patterns of sarcolemmal disruption.

Straub V, Rafael JA, Chamberlain JS, Campbell KP - J. Cell Biol. (1997)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of, Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City, Iowa 52242, USA.

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 alpha2-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.

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EBD staining (a) and H&E staining (b) on 7-μm cryosections from a 7-wk-old dy/dy diaphragm. The few EBD-positive fibers in dy/dy skeletal muscle always showed necrotic features in the corresponding H&E stain. The nuclei of infiltrating  immune cells were also detected by the EBD. Bars, 100 μm.
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Figure 7: EBD staining (a) and H&E staining (b) on 7-μm cryosections from a 7-wk-old dy/dy diaphragm. The few EBD-positive fibers in dy/dy skeletal muscle always showed necrotic features in the corresponding H&E stain. The nuclei of infiltrating immune cells were also detected by the EBD. Bars, 100 μm.

Mentions: The sections from injected dy/dy and dy2J/dy2J mice showed only occasional EBD-positive fibers in the diaphragm (Fig. 7) or the femoral quadriceps muscle (Fig. 6 f). The low level of intracellular fiber staining was a constant feature of the muscles we examined from dy/dy and dy2J/ dy2J mice (Table I). The dye-positive fibers always showed necrotic features according to H&E staining (Fig. 7). They appeared singly and never showed grouping, which is characteristic for mdx or Dp71 transgenic/mdx mice (Fig. 6). There were no differences in the extent or intensity of dye accumulation and distribution in skeletal muscles between dy/dy and dy2J/dy2J mice. In contrast to mdx mice, we never found EBD staining in the cardiac muscle of dy/dy and dy2J/dy2J mice.


Animal models for muscular dystrophy show different patterns of sarcolemmal disruption.

Straub V, Rafael JA, Chamberlain JS, Campbell KP - J. Cell Biol. (1997)

EBD staining (a) and H&E staining (b) on 7-μm cryosections from a 7-wk-old dy/dy diaphragm. The few EBD-positive fibers in dy/dy skeletal muscle always showed necrotic features in the corresponding H&E stain. The nuclei of infiltrating  immune cells were also detected by the EBD. Bars, 100 μm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2139791&req=5

Figure 7: EBD staining (a) and H&E staining (b) on 7-μm cryosections from a 7-wk-old dy/dy diaphragm. The few EBD-positive fibers in dy/dy skeletal muscle always showed necrotic features in the corresponding H&E stain. The nuclei of infiltrating immune cells were also detected by the EBD. Bars, 100 μm.
Mentions: The sections from injected dy/dy and dy2J/dy2J mice showed only occasional EBD-positive fibers in the diaphragm (Fig. 7) or the femoral quadriceps muscle (Fig. 6 f). The low level of intracellular fiber staining was a constant feature of the muscles we examined from dy/dy and dy2J/ dy2J mice (Table I). The dye-positive fibers always showed necrotic features according to H&E staining (Fig. 7). They appeared singly and never showed grouping, which is characteristic for mdx or Dp71 transgenic/mdx mice (Fig. 6). There were no differences in the extent or intensity of dye accumulation and distribution in skeletal muscles between dy/dy and dy2J/dy2J mice. In contrast to mdx mice, we never found EBD staining in the cardiac muscle of dy/dy and dy2J/dy2J mice.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of, Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City, Iowa 52242, USA.

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 alpha2-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.

Show MeSH
Related in: MedlinePlus