Deconinck N, Tinsley J, De Backer F, Fisher R, Kahn D, Phelps S, Davies K, Gillis J M
Département de Physiologie, Université Catholique de Louvain, Brussels, Belgium.
Nat Med. 1997 Nov;3(11):1216-21. doi: 10.1038/nm1197-1216.
Dystrophin-deficient mice (mdx) expressing a truncated (trc) utrophin transgene show amelioration of the dystrophic phenotype. Here we report a multifunctional study demonstrating that trcutrophin expression leads to major improvements of the mechanical performance of muscle (that is, force development, mechanical resistance to forced lengthenings and maximal spontaneous activity) and of the maintenance of the intracellular calcium homeostasis. These are two essential functions of muscle fibers, known to be impaired in mdx mouse muscles and Duchenne muscular dystrophy (DMD) patients. Our results bring strong support to the hypothesis that muscle wasting in dystrophin-deficient DMD patients could be prevented by upregulation of utrophin.
表达截短型（trc）抗肌萎缩蛋白转基因的抗肌萎缩蛋白缺陷小鼠（mdx）显示出营养不良表型的改善。在此，我们报告一项多功能研究，证明trc抗肌萎缩蛋白的表达可显著改善肌肉的机械性能（即力量发展、对强制拉长的机械抗性和最大自发活动）以及细胞内钙稳态的维持。这是肌纤维的两个基本功能，已知在mdx小鼠肌肉和杜兴氏肌营养不良症（DMD）患者中受损。我们的结果为以下假设提供了有力支持：通过上调抗肌萎缩蛋白可预防抗肌萎缩蛋白缺陷的DMD患者的肌肉萎缩。
