FUNCTIONAL RESCUE OF THE SARCOGLYCAN COMPLEX IN THE BIO-14.6 HAMSTER USING DELTA-SARCOGLYCAN GENE-TRANSFER

Four types of limb-girdle muscular dystrophy (LGMD) are known to be ca used by mutations in distinct sarcoglycan genes. The BIO 14.6 hamster is a model for sarcoglycan-deficient LGMD with a deletion in the delta -sarcoglycan (delta-SG) gene. We investigated the function of the sarc oglycan complex and the feasibility of sarcoglycan gene transfer for L GMD using a recombinant delta-SG adenovirus in the BIO 14.6 hamster. W e demonstrate extensive long-term expression of delta-sarcoglycan and rescue of the entire sarcoglycan complex, as well as restored stable a ssociation of alpha-dystroglycan with the sarcolemma. Importantly, mus cle fibers expressing delta-sarcoglycan lack morphological markers of muscular dystrophy and exhibit restored plasma membrane integrity. In summary, the sarcoglycan complex is requisite for the maintenance of s arcolemmal integrity, and primary mutations in individual sarcoglycan components can be corrected in vivo.