Functional Deficits in nNOS mu-Deficient Skeletal Muscle: Myopathy in nNOS Knockout Mice
Justin M Percival, Kendra NE Anderson, Paul Gregorevic, Jeffrey S Chamberlain, Stanley C Froehner
PLOS ONE | PUBLIC LIBRARY SCIENCE | Published : 2008
Skeletal muscle nNOSmu (neuronal nitric oxide synthase mu) localizes to the sarcolemma through interaction with the dystrophin-associated glycoprotein (DAG) complex, where it synthesizes nitric oxide (NO). Disruption of the DAG complex occurs in dystrophinopathies and sarcoglycanopathies, two genetically distinct classes of muscular dystrophy characterized by progressive loss of muscle mass, muscle weakness and increased fatigability. DAG complex instability leads to mislocalization and downregulation of nNOSmu; but this is thought to play a minor role in disease pathogenesis. This view persists without knowledge of the role of nNOS in skeletal muscle contractile function in vivo and has inf..View full abstract
Awarded by NIH
Awarded by EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH &HUMAN DEVELOPMENT
Awarded by NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
This work was supported by NIH grants NS046788 and NS33145 (S.C.F.), NIH grant U54 HD047175 (S.C.F. and J.S.C.), a Parent Project for Muscular Dystrophy Research Fellowship (J.M.P) and a MDA Development Grant (J.M.P).