Pathological analysis of muscle hypertrophy and degeneration in muscular dystrophy in gamma-sarcoglycan-deficient mice

Neuromuscul Disord. 2003 Mar;13(3):193-206. doi: 10.1016/s0960-8966(02)00220-1.


While calf muscle hypertrophy is a striking diagnostic finding in sarcoglycanopathy, as it is in Duchenne and Becker muscular dystrophies, its pathogenetic mechanism remains unknown. gamma-Sarcoglycan, one of the subunits of the sarcoglycan complex, is the protein responsible for gamma-sarcoglycanopathy. To elucidate the pathogenetic mechanisms of muscle hypertrophy and degeneration in muscular dystrophy, we utilized a mutant mouse as a model animal. In this study, we generated gamma-sarcoglycan-deficient (gsg-/-) mice by gene targeting. The gsg-/- mice described here, similar to the gsg-/- mice reported previously (J Cell Biol 142 (1998) 1279), demonstrated skeletal and cardiac muscle degeneration. The limb, shoulder, and pelvic muscles of the gsg-/- mice exhibited progressive muscle hypertrophy and weakness with age, and the findings were similar to those seen in other mouse models for limb-girdle and Duchenne muscular dystrophy. We found that the number of muscle fibers increased with age, and most of the fibers in the hypertrophic muscle were centrally nucleated regenerating fibers. Therefore, muscle hypertrophy of the gsg-/- mice may result from an increase of the number of muscle fibers and probable fiber branching and may not be due to the pseudohypertrophy caused by fibrous and fat tissue replacement, as has been long supposed in muscular dystrophy. The muscle pathology became more 'dystrophic' in mice over 1 year of age when there was a marked variation in fiber size with interstitial fibrosis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Basement Membrane / physiopathology
  • Blotting, Southern
  • Cell Line
  • Cytoskeletal Proteins / deficiency*
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism
  • DNA, Complementary
  • Disease Models, Animal
  • Dystroglycans
  • Female
  • Growth Substances
  • Homozygote
  • Humans
  • Hypertrophy
  • Immunohistochemistry
  • Male
  • Membrane Glycoproteins / deficiency*
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Mutant Strains
  • Muscle Fibers, Skeletal / metabolism
  • Muscle Fibers, Skeletal / pathology
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology*
  • Muscular Dystrophy, Animal / genetics
  • Muscular Dystrophy, Animal / metabolism
  • Muscular Dystrophy, Animal / pathology*
  • Muscular Dystrophy, Animal / physiopathology
  • Peptides*
  • Phenotype
  • Regeneration / physiology
  • Sarcoglycans
  • Survival


  • Cytoskeletal Proteins
  • DAG1 protein, human
  • DNA, Complementary
  • Growth Substances
  • Membrane Glycoproteins
  • Peptides
  • Sarcoglycans
  • Dystroglycans
  • progressin