Holt K H, Lim L E, Straub V, Venzke D P, Duclos F, Anderson R D, Davidson B L, Campbell K P
Howard Hughes Medical Institute, Department of Physiology and Biophysics, University of Iowa College of Medicine, Iowa City, Iowa 52242, USA.
Mol Cell. 1998 May;1(6):841-8. doi: 10.1016/s1097-2765(00)80083-0.
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 delta-sarcoglycan (delta-SG) gene. We investigated the function of the sarcoglycan complex and the feasibility of sarcoglycan gene transfer for LGMD using a recombinant delta-SG adenovirus in the BIO 14.6 hamster. We demonstrate extensive long-term expression of delta-sarcoglycan and rescue of the entire sarcoglycan complex, as well as restored stable association of alpha-dystroglycan with the sarcolemma. Importantly, muscle 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 sarcolemmal integrity, and primary mutations in individual sarcoglycan components can be corrected in vivo.
已知四种类型的肢带型肌营养不良症（LGMD）是由不同的肌聚糖基因发生突变所致。BIO 14.6仓鼠是一种因δ-肌聚糖（δ-SG）基因缺失而导致肌聚糖缺乏的LGMD模型。我们使用重组δ-SG腺病毒，在BIO 14.6仓鼠中研究了肌聚糖复合物的功能以及肌聚糖基因转移治疗LGMD的可行性。我们证明了δ-肌聚糖能够长期广泛表达，整个肌聚糖复合物得以挽救，同时α- dystroglycan与肌膜的稳定结合得以恢复。重要的是，表达δ-肌聚糖的肌纤维缺乏肌营养不良的形态学标志物，并且其质膜完整性得以恢复。总之，肌聚糖复合物是维持肌膜完整性所必需的，单个肌聚糖成分的原发性突变在体内可以得到纠正。
