Duchenne型肌营养不良症发病机制

Duchenne型肌营养不良症是我国常见的X连锁隐性遗传性肌病。目前广泛应用的动物模型是mdx小鼠,但其没有很好地模拟人类疾病特点。最近,Sacco等报导了一个新的小鼠模型mdx/mTRG2,它不仅有抗肌萎缩蛋白的缺陷,还有端粒酶的缺失,较好地模拟了人类疾病的症状。通过该模型,人们认识到抗肌萎缩蛋白的缺陷引起肌细胞退化,肌肉干细胞被激活对抗其退化,但干细胞的过度增殖又导致端粒长度下降,引起肌肉干细胞增殖能力的衰竭,最终产生了肌营养不良的表型。该模型使人们对Duchenne型肌营养不良症的发病机制有了进一步的理解,为其治疗提供了新的研究平台。

The pathogenesis of Duchenne muscular dystrophy

Duchenne muscular dystrophy is a common X-linked recessive muscular disease in China.The most widely used animal model is the mdx mouse,but it doesn’t analogue the characteristics of human disease very well.Recently,Sacco et al have reported a new mouse model-mdx/mTRG2which was not only dystrophin deficiency but also telomerase knockout.This model simulates the symptoms of human Duchenne muscular dystrophy particularly well.Further studies have showed that dystrophin mutation leads to myogenic stem cell proliferation for compensation,and over proliferation results in telomere shortening,which causes exhaustion in the myogenic stem cells and muscular dystrophy.This model provides a novel insight into the pathogenesis of Duchenne muscular dystrophy,as well as provides a new platform for its researches.