N-terminal α Dystroglycan (αDG-N): A Potential Serum Biomarker for Duchenne Muscular Dystrophy
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Date
2018-03
Authors
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Publisher
IOS Press
Abstract
Background: 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. Objectives: 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. Methods: ELISAs of immobilized patient or mouse serum and Western blots were used to assess αDG-N expression. Results: 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 DMD 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. Conclusions: 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.
Description
Biological Sciences: 2nd Place (The Ohio State University Edward F. Hayes Graduate Research Forum)
Keywords
Dystroglycan, Biomarker, Dystrophin, Muscular Dystrophy, Utrophin
Citation
Crowe, K. E., Shao, G., Flanigan, K. M., & Martin, P. T. (2016). N-terminal α Dystroglycan (αDG-N): A Potential Serum Biomarker for Duchenne Muscular Dystrophy. Journal of Neuromuscular Diseases, 3(2), 247–260. http://doi.org/10.3233/JND-150127