Muscle Biology Unit, Division for Cell and Matrix Biology, Department of Experimental Medical Science, BMC B12, University of Lund, Lund 221 84, Sweden.
Muscle Nerve. 2010 Jul;42(1):30-7. doi: 10.1002/mus.21616.
Several approaches to treat laminin alpha2 chain-deficient congenital muscular dystrophy (MDC1A) in mouse models have been undertaken. Most have shown promising results in young animals. However, older animals have only been characterized to some extent. Herein we analyze the lifespan of laminin alpha2 chain-deficient mice with transgenic overexpression of laminin alpha1 chain. Further outcome measures included internalized myonuclei, heart fibrosis, grip strength, and serum creatine kinase activity. We show that laminin alpha2-chain-deficient animals that overexpress laminin alpha1 chain survive to up to 1.5-2 years of age. Furthermore, they displayed improved skeletal and heart muscle morphology, near-normal muscle strength, and normalized creatine kinase levels. Such an improvement of the dystrophic phenotype that persists to old age has not been previously demonstrated in mice. Our findings hold promise with regard to the efficient treatment of MDC1A patients in the future.
已经采用了几种方法来治疗层粘连蛋白 α2 链缺陷型先天性肌营养不良症（MDC1A）的小鼠模型。大多数方法在幼小动物中显示出有希望的结果。然而，对老年动物的研究还在一定程度上进行。在此，我们分析了过表达层粘连蛋白 α1 链的层粘连蛋白 α2 链缺陷型小鼠的寿命。进一步的结果测量包括内化肌核、心脏纤维化、握力和血清肌酸激酶活性。我们表明，过表达层粘连蛋白 α1 链的层粘连蛋白 α2 链缺陷型动物可存活至 1.5-2 岁。此外，它们表现出改善的骨骼和心肌形态、接近正常的肌肉力量和正常的肌酸激酶水平。这种在老年时持续存在的肌营养不良表型的改善以前在小鼠中尚未得到证明。我们的研究结果为未来 MDC1A 患者的有效治疗提供了希望。
