Functional rescue of the sarcoglycan complex in the BIO 14.6 hamster using δ-sarcoglycan gene transfer

Abstract

Four types of limb-girdle muscular dystrophy (LGMD) are known to be caused by mutations in distinct sarcoglycan genes. The BIO 14.6 hamster is a model for sarcoglycan-deficient LGMD with a deletion in the δ-sarcoglycan (δ-SG) gene. We investigated the function of the sarcoglycan complex and the feasibility of sarcoglycan gene transfer for LGM D using a recombinant δ-SG adenovirus in the BIO 14.6 hamster. We demonstrate extensive long-term expression of δ-sarcoglycan and rescue of the entire sarcoglycan complex, as well as restored stable association of α-dystroglycan with the sarcolemma. Importantly, muscle fibers expressing δ-sarcoglycan lack morphological markers of muscular dystrophy and exhibit restored plasma membrane integrity. In summary, the sarcoglycan complex is requisite for the maintenance of sarcolemmal integrity, and primary mutations in individual sarcoglycan components can be corrected in vivo.