Proteomic Profiling of the Dystrophin-Deficient Brain.

Abstract

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.