Master of Science
Meredith Protas, PhD
Tom Hartl, PhD
Roger Lawrence, PhD
Duchenne muscular dystrophy (DMD) is a genetic disorder caused by a mutation in the DMD gene which leads to progressive muscle degeneration and ultimately death. The Dystrophin protein that is non-functioning within this disorder is a main component of the Dystrophin-associated glycoprotein complex (DGC) that stabilizes the plasma membrane of muscle cells. The DGC is maintained by proteoglycans, which are comprised of linear glycosaminoglycans (GAGs) attached to a protein core. Proteoglycans and their associated GAG chains have been found to play an important role in regulating the development and regeneration of muscle cells. However, no comprehensive profiling of the change in structure and expression of all GAGs in DMD pathology has been carried out. Here we show that the GAG chondroitin sulfate (CS) is elevated in dystrophic mouse tissues, and that the 4-O-sulfated species of CS is also elevated. We also show for the first-time that in DMD muscles, there are elevated levels of both total heparan sulfate (HS) and the 6-O-sulfated HS species. These are important mechanisms to understand as they may pertain to DMD specific disease biology and thus could aid in the development of novel therapeutics for the disorder.
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