Use of Animal Models to Understand Human Muscular Dystrophy

In the decade following the identification of mutations in the dystrophin genein Duchenne (1 ) and Becker (2 ) muscular dystrophies (DMD/BMD), defects in components of the dystrophin-glycoprotein complex (DGC), which links F-actin in the cytoskeleton with laminin in the extra cellular matrix, have been shown to result in several human MD syndromes (3 ). Defects in α-, β-, γ-, and δ-sarcoglycans, which are components of the DGC, are associated with limb-girdle MDs (LGMD) 2D, E, C, and F, respectively; laminin α₂ -chain mutations have been shown to result in congenital MD (4 ). Defects in non-DGC components that cause include the calpain 3 in LGMD2A (4 ), expansion of a CTG repeat in the 3′ untranslated region of a serine threonine kinase (myotonic dystrophy protein kinase [DMPK]) in myotonic dystrophy (DM) (5 ), and mutations in a novel nuclear protein in Emery-Dreifuss MD (6 ).