Bartoli M, Poupiot J, Vulin A, Fougerousse F, Arandel L, Daniele N, Roudaut C, Noulet F, Garcia L, Danos O, Richard I
Généthon, CNRS UMR8115, Evry, France.
Gene Ther. 2007 May;14(9):733-40. doi: 10.1038/sj.gt.3302928. Epub 2007 Mar 1.
Myostatin is a negative regulator of muscle mass whose inhibition has been proposed as a therapeutic strategy for muscle-wasting conditions. Indeed, blocking myostatin action through different strategies has proved beneficial for the pathophysiology of the dystrophin-deficient mdx mouse. In this report, we tested the inhibition of myostatin by AAV-mediated expression of a mutated propeptide in animal models of two limb-girdle muscular dystrophies: LGMD2A caused by mutations in the calpain 3 (CAPN3) gene and LGMD2D caused by mutations in the alpha-sarcoglycan gene (SGCA). In the highly regenerative Sgca-null mice, survival of the alpha-sarcoglycan-deficient muscle fibers did not improve after transfer of the myostatin propeptide. In calpain 3-deficient mice, a boost in muscle mass and an increase in absolute force were obtained, suggesting that myostatin inhibition could constitute a therapeutic strategy in this predominantly atrophic disorder.
肌生成抑制素是肌肉量的负调节因子，抑制该因子已被提议作为治疗肌肉萎缩病症的一种策略。事实上，通过不同策略阻断肌生成抑制素的作用已被证明对肌营养不良蛋白缺陷的mdx小鼠的病理生理学有益。在本报告中，我们在两种肢带型肌营养不良症的动物模型中测试了通过腺相关病毒介导的突变前肽表达对肌生成抑制素的抑制作用：由钙蛋白酶3（CAPN3）基因突变引起的LGMD2A和由α-肌聚糖基因（SGCA）突变引起的LGMD2D。在高度再生的Sgca基因缺失小鼠中，转移肌生成抑制素前肽后，α-肌聚糖缺陷型肌纤维的存活率并未提高。在钙蛋白酶3缺陷型小鼠中，肌肉量增加且绝对力量增强，这表明抑制肌生成抑制素可能是这种以萎缩为主的疾病的一种治疗策略。
