Funk Steven D, Miner Jeffrey H
J Clin Invest. 2017 Mar 1;127(3):798-800. doi: 10.1172/JCI92847. Epub 2017 Feb 20.
Muscular dystrophies result from a defect in the linkage between the muscle fiber cytoskeleton and the basement membrane (BM). Congenital muscular dystrophy type MDC1A is caused by mutations in laminin α2 that either reduce its expression or impair its ability to polymerize within the muscle fiber BM. Defects in this BM lead to muscle fiber damage from the force of contraction. In this issue of the JCI, McKee and colleagues use a laminin polymerization-competent, designer chimeric BM protein in vivo to restore function of a polymerization-defective laminin, leading to normalized muscle structure and strength in a mouse model of MDC1A. Delivery of such a protein to patients could ameliorate many aspects of their disease.
肌肉营养不良症是由肌纤维细胞骨架与基底膜（BM）之间的连接缺陷引起的。先天性MDC1A型肌肉营养不良症是由层粘连蛋白α2的突变引起的，这些突变要么降低其表达，要么损害其在肌纤维基底膜内聚合的能力。这种基底膜的缺陷会导致收缩力引起的肌纤维损伤。在本期《临床研究杂志》中，麦基及其同事在体内使用一种具有层粘连蛋白聚合能力的设计嵌合基底膜蛋白，以恢复聚合缺陷型层粘连蛋白的功能，从而使MDC1A小鼠模型的肌肉结构和力量正常化。将这种蛋白质输送给患者可以改善其疾病的许多方面。
