title: N-terminal α Dystroglycan (αDG-N): A Potential Serum Biomarker for Duchenne Muscular Dystrophy.
abstract: Duchenne Muscular Dystrophy (DMD) is a severe, progressive, neuromuscular disorder of childhood. While a number of serum factors have been identified as potential biomarkers of DMD, none, as yet, are proteins within the dystrophin-associated glycoprotein (DAG) complex.
  
  
  
  We have developed an immobilized serum ELISA assay to measure the expression of a constitutively cleaved and secreted component of the DAG complex, the N-terminal domain of α dystroglycan (αDG-N), and assayed relative expression in serum from muscular dystrophy patients and normal controls.
  
  
  
  ELISAs of immobilized patient or mouse serum and Western blots were used to assess αDG-N expression.
  
  
  
  Immobilization of diluted serum on ELISA plates was important for this assay, as methods to measure serum αDG-N in solution were less robust. αDG-N ELISA signals were significantly reduced in DMD serum (27±3% decrease, n = 9, p < 0.001) relative to serum from otherwise normal controls (n = 38), and calculated serum αDG-N concentrations were reduced in DMD relative to normal (p < 0.01) and Becker Muscular Dystrophy (n = 11, p < 0.05) patient serum. By contrast, ELISA signals from patients with Inclusion Body Myositis were not different than normal (4±3% decrease, n = 8, p = 0.99). αDG-N serum signals were also significantly reduced in utrophin-deficient mdx mice as compared to mdx and wild type mice.
  
  
  
  Our results are the first demonstration of a component of the DAG complex as a potential serum biomarker in DMD. Such a serum measure could be further developed as a tool to help reflect overall muscle DAG complex expression or stability.
authors.affiliation: Graduate Program in Molecular Cellular and Developmental Biology, The Ohio State University, Columbus, OH, USA.
authors.forename: Kelly E
authors.initials: KE
authors.lastname: Crowe
authors.affiliation: Center for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
authors.forename: Guohong
authors.initials: G
authors.lastname: Shao
authors.affiliation: Center for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.|Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, USA.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Flanigan
authors.affiliation: Center for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.|Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, USA.
authors.forename: Paul T
authors.initials: PT
authors.lastname: Martin
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D015153:Blotting, Western; D016022:Case-Control Studies; D049030:Dystroglycans / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D018101:Mice, Inbred mdx; D018345:Mice, Knockout; D009137:Muscular Dystrophy, Animal / Q000097:blood; D020388:Muscular Dystrophy, Duchenne / Q000097:blood*; D018979:Myositis, Inclusion Body / Q000097:blood; D049411:Utrophin / Q000235:genetics
chemical_list: D015415:Biomarkers; C483081:DAG1 protein, human; C000624607:Dag1 protein, mouse; C483600:Utrn protein, mouse; D049411:Utrophin; D049030:Dystroglycans
keywords: Dystroglycan; biomarker; dystrophin; muscular dystrophy; utrophin