Functional rescue of the sarcoglycan complex in the BIO 14.6 hamster using δ-sarcoglycan gene transfer
Functional rescue of the sarcoglycan complex in the BIO 14.6 hamster using δ-sarcoglycan gene transfer
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DOI：
10.1016/s1097-2765(00)80083-0
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发表时间：
1998-05-01
期刊：
影响因子：
16
通讯作者：
Campbell, KP
中科院分区：
文献类型：
--
作者：
Holt, KH;Lim, LE;Campbell, KP
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突变引起的。BIO 14.6仓鼠是肌聚糖缺陷型LGMD的模型，其中δ-肌聚糖（δ-SG）基因缺失。我们研究了肌聚糖复合物的功能以及使用重组delta-SG腺病毒在BIO 14.6仓鼠中转移肌聚糖基因治疗LGMD的可行性。我们证明了δ-肌聚糖的广泛长期表达和整个肌聚糖复合物的拯救，以及α-肌营养不良蛋白聚糖与肌膜的恢复稳定关联。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，并表现出恢复的质膜完整性。总之，肌聚糖复合物是维持肌膜完整性所必需的，并且单个肌聚糖组分中的原发性突变可以在体内得到纠正。
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.