themolecularbasisofmusculardystrophy.pptVIP

The Molecular Basis of Muscular Dystrophy;肌肉萎缩症（假性肥大肌营养不良）;What Are Muscular Dystrophies?;Different Types of MD;Guillaume Duchenne;Why are DMD and BMD discussed together?;The gene of Dystrophin(抗肌肉萎缩蛋白) ; The exons are put together for code assembly during a process called splicing. Due to its length the Dystrophin gene is relatively vulnerable for rearrangements (mutations) ;X-linked recessive diseases; The protein dystrophin reside in the membrane skeleton of striatedmuscle(横纹肌) cells. It is important for the strength and flexibility of the muscle fiber membranes.;Dystrophin are rod-shaped dimers（杆状二聚物） beneath the plasma membrane ;laminin; On their cytoplasmic side ,dystrophin molecules are attached to actin filaments, and on their membrane side, they are attached to a cluster of dystophin-associated proteins (DAPs), in turn, are linked on their extracellular surface to components of the basement membrane that surround these contractile(有收缩性的) cells. Taken together, these various proteins form a functional pathway linking the extracellular matrix with the internal cytoskeleton. In addition, dystrophin provides structural support for the plasma membrane as the muscle fiber repeatedly contracts and relaxes. 抗肌萎缩蛋白的C端连接着一系列与抗肌萎缩蛋白相关的糖蛋白 (DAPs) ，进而与收缩细胞的细胞外基质成分连接.内部端（氨基酸端）连接肌动蛋白（肌动蛋白是肌细胞的骨架），所以说抗肌萎缩蛋白是连接肌细胞内部骨架和细胞膜外的重要桥梁，当肌肉收缩时，它起到稳定肌肉细胞的作用。; How mutations cause Duchenne and Becker dystrophy?; DMD ——Many mutations in the gene disrupt the reading frame—“out of frame”， and thus cause the premature abortion（流产） of the synthesis of the dystrophin, BMD ——Numerous mutations are “in-frame”, and conserve the reading frame. Despite a large internal deletion, a truncated（删节的） but mostly functional dystrophin is produced. In these BMD patients, the extent and progression of the muscle weakness is less severe. ;如果基因的突变没有完全打乱 “三子一窝”的基因阅读框， 也就说基因字母（核酣酸）缺 失或增加的数量能被3整除， 没有余数。这种情况下抗肌萎 缩蛋白被缩短或者拉长，同时 基因的改变发生在非关键区 域