Disruption of the beta-sarcoglycan gene reveals pathogenetic complexity of limb-girdle muscular dystrophy type 2E

Mol Cell. 2000 Jan;5(1):141-51. doi: 10.1016/s1097-2765(00)80410-4.


Limb-girdle muscular dystrophy type 2E (LGMD 2E) is caused by mutations in the beta-sarcoglycan gene, which is expressed in skeletal, cardiac, and smooth muscle. beta-sarcoglycan-deficient (Sgcb-null) mice developed severe muscular dystrophy and cardiomyopathy with focal areas of necrosis. The sarcoglycan-sarcospan and dystroglycan complexes were disrupted in skeletal, cardiac, and smooth muscle membranes. epsilon-sarcoglycan was also reduced in membrane preparations of striated and smooth muscle. Loss of the sarcoglycan-sarcospan complex in vascular smooth muscle resulted in vascular irregularities in heart, diaphragm, and kidneys. Further biochemical characterization suggested the presence of a distinct epsilon-sarcoglycan complex in skeletal muscle that was disrupted in Sgcb-null mice. Thus, perturbation of vascular function together with disruption of the epsilon-sarcoglycan-containing complex represents a novel mechanism in the pathogenesis of LGMD 2E.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cardiomyopathies / genetics
  • Cardiomyopathies / pathology
  • Cytoskeletal Proteins / deficiency
  • Cytoskeletal Proteins / genetics*
  • Cytoskeletal Proteins / physiology
  • Dystroglycans
  • Dystrophin / genetics
  • Lung / pathology
  • Membrane Glycoproteins / deficiency
  • Membrane Glycoproteins / genetics*
  • Membrane Glycoproteins / physiology
  • Mice
  • Mice, Knockout
  • Microsomes / pathology
  • Muscle, Skeletal / pathology*
  • Muscular Dystrophy, Animal / genetics*
  • Muscular Dystrophy, Animal / pathology*
  • Myocardium / pathology*
  • Necrosis


  • Cytoskeletal Proteins
  • Dystrophin
  • Membrane Glycoproteins
  • Dystroglycans