title: Loss of sarcolemmal nNOS is common in acquired and inherited neuromuscular disorders.
abstract: OBJECTIVE
  Neuronal nitric oxide synthase (nNOS), normally expressed at the sarcolemmal membrane, is known to be mislocalized to the sarcoplasm in several forms of muscular dystrophy. Our objectives were to characterize further the range of patients manifesting aberrant nNOS sarcolemmal immunolocalization and to study nNOS localization in animal models of nondystrophic myopathy.
  
  
  METHODS
  We carried out a retrospective cross-sectional study. We performed immunofluorescent staining for nNOS on biopsy specimens from 161 patients with acquired and nondystrophin inherited neuromuscular conditions. The localization of sarcolemmal nNOS correlated with mobility and functional status. Muscle specimens from mouse models of steroid-induced and starvation-related atrophy were studied for qualitative and quantitative nNOS expression.
  
  
  RESULTS
  Sarcolemmal nNOS staining was abnormal in 42% of patients with inherited myopathic conditions, 25% with acquired myopathic conditions, 57% with neurogenic conditions, and 93% with hypotonia. Interestingly, we found significant associations between mobility status or muscle function and sarcolemmal nNOS expression. Furthermore, mouse models of catabolic stress also demonstrated mislocalization of sarcolemmal nNOS.
  
  
  CONCLUSIONS
  Our analyses indicate that nNOS mislocalization is observed in a broad range of nondystrophic neuromuscular conditions associated with impaired mobility status and catabolic stress. Our findings suggest that the assessment of sarcolemmal localization of nNOS represents an important tool for the evaluation of muscle biopsies of patients with a variety of inherited and acquired forms of neuromuscular disorders.
authors.affiliation: Department of Neurology, Johns Hopkins University School of Medicine, 733 North Broadway BRB 529, Baltimore, MD 21205, USA.
authors.forename: E L
authors.initials: EL
authors.lastname: Finanger Hedderick
authors.forename: J L
authors.initials: JL
authors.lastname: Simmers
authors.forename: A
authors.initials: A
authors.lastname: Soleimani
authors.forename: E
authors.initials: E
authors.lastname: Andres-Mateos
authors.forename: R
authors.initials: R
authors.lastname: Marx
authors.forename: D C
authors.initials: DC
authors.lastname: Files
authors.forename: L
authors.initials: L
authors.lastname: King
authors.forename: T O
authors.initials: TO
authors.lastname: Crawford
authors.forename: A M
authors.initials: AM
authors.lastname: Corse
authors.forename: R D
authors.initials: RD
authors.lastname: Cohn
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D005455:Fluorescent Antibody Technique; D006801:Humans; D007223:Infant; D051379:Mice; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D009137:Muscular Dystrophy, Animal / Q000235:genetics / Q000378:metabolism; D009468:Neuromuscular Diseases / Q000235:genetics / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000235:genetics / Q000378:metabolism*; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012508:Sarcolemma / Q000235:genetics / Q000378:metabolism*; D012589:Sciuridae
chemical_list: D052248:Nitric Oxide Synthase Type I