Murphy Sandra, Ohlendieck Kay
Department of Biology, Maynooth University, National University of Ireland Maynooth, Callan Building, North Campus, Maynooth, Co. Kildare, Ireland.
Methods Mol Biol. 2018;1687:91-105. doi: 10.1007/978-1-4939-7374-3_7.
Duchenne muscular dystrophy is a highly progressive neuromuscular disorder caused by primary abnormalities in the Dmd gene encoding the membrane cytoskeletal protein dystrophin. Dystrophinopathies are multi-systems disorders that are characterized by severe skeletal muscle wasting, with loss of independent ambulation in the early teenage years, followed by cardio-respiratory complications and premature death. Nonprogressive cognitive impairments are estimated to affect approximately one-third of dystrophic children. To identify the molecular mechanisms behind the impaired brain function in dystrophinopathy, liquid chromatography-based mass spectrometry offers an unbiased and technology-driven approach. In this chapter, we give a detailed description of a label-free mass spectrometric method to investigate proteome-wide changes in the dystrophin-deficient brain from a genetic mouse model of Duchenne muscular dystrophy.
杜兴氏肌营养不良症是一种高度进展性的神经肌肉疾病，由编码膜细胞骨架蛋白抗肌萎缩蛋白的Dmd基因的原发性异常引起。抗肌萎缩蛋白病是多系统疾病，其特征是严重的骨骼肌萎缩，在青少年早期丧失独立行走能力，随后出现心肺并发症和过早死亡。据估计，非进行性认知障碍影响约三分之一的营养不良儿童。为了确定抗肌萎缩蛋白病中脑功能受损背后的分子机制，基于液相色谱的质谱提供了一种无偏见且技术驱动的方法。在本章中，我们详细描述了一种基于无标记质谱的方法，用于研究来自杜兴氏肌营养不良症基因小鼠模型的抗肌萎缩蛋白缺陷型大脑中的全蛋白质组变化。
