Selective loss of sarcolemmal nitric oxide synthase in Becker muscular dystrophy

摘要: Becker muscular dystrophy is an X-linked disease due to mutations of the dystrophin gene. We now show that neuronal-type nitric oxide synthase (nNOS), identified enzyme in complex, uniquely absent from skeletal muscle plasma membrane many human patients and mouse models dystrophinopathy. An NH2-terminal domain nNOS directly interacts with alpha 1-syntrophin but not other proteins complex analyzed. However, does associate on sarcolemma transgenic mdx mice expressing truncated proteins. This suggests a ternary interaction nNOS, 1-syntrophin, central vivo, conclusion supported by developmental studies muscle. These data indicate proper assembly dependent upon structure rodlike have implications for design dystrophin-containing vectors gene therapy.