Disruption of the β-Sarcoglycan Gene Reveals Pathogenetic Complexity of Limb-Girdle Muscular Dystrophy Type 2E
2000; Elsevier BV; Volume: 5; Issue: 1 Linguagem: Inglês
10.1016/s1097-2765(00)80410-4
ISSN1097-4164
AutoresMadeleine Durbeej, Ronald D. Cohn, Ronald F. Hrstka, Steven A. Moore, Valérie Allamand, Beverly L. Davidson, Roger A. Williamson, Kevin P. Campbell,
Tópico(s)Cardiomyopathy and Myosin Studies
ResumoLimb-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.
Referência(s)