Grant: Project Grant

Muscular dystrophy is a life-threatening muscular disorder, to which there is no cure. Part of the difficulty in treating this disorder is the fact that this is a genetic disease that affects key proteins that maintain muscle integrity. The purpose of this study is to better understand the regulation of structural proteins by further exploring the robust effect of GCN5 on the expression of dystrophin and other important structural proteins in muscle. GCN5 is a protein known to modify other proteins through a process called acetylation. During this process GCN5 adds an acetyl group to specific proteins in order to alter their function. While examining mice that specifically lack the expression of GCN5 in muscle we unexpectedly found a reduction in gene and protein expression of dystrophin. Upon further examination we found that these mice exhibited similar phenotypes to mice with muscular dystrophy, called mdx mice. With our preliminary evidence, we speculate that the reduction in structural protein expression is controlled by GCN5-directed acetylation of YY1, a previously known modulator of dystrophin. A better understanding of the role of GCN5 in muscular dystrophy may lead to potential treatment options, whereby boosting structural proteins could compensate for existing structural defects, a well known approach for muscular dystrophy therapy development.