Functional capacity of dystrophins carrying deletions in the N-terminal actin-binding domain

Abstract

Duchenne muscular dystrophy and Becker muscular dystrophy (BMD) are caused by mutations in the dystrophin gene. Although many in-frame deletions in the dystrophin gene lead to mild cases of BMD, truncations within the N-terminal actin-binding domain (ABD1) typically decrease dystrophin expression and lead to more severe cases of BMD. Because of the large reduction in protein expression, the functional capacity of dystrophin proteins deleted for subportions of ABD1 has been difficult to ascertain. ABD1 contains three actin-binding sequences designated ABS1-3. In the present study, we examined the pathophysiological effects of in-frame actin-binding sequence deletions in the context of a highl..