Glycogen accumulation in smooth muscle of a Pompe disease mouse model.

Journal Article (Journal Article)

Pompe disease is a lysosomal storage disease caused by mutations within the GAA gene, which encodes acid α-glucosidase (GAA)-an enzyme necessary for lysosomal glycogen degradation. A lack of GAA results in an accumulation of glycogen in cardiac and skeletal muscle, as well as in motor neurons. The only FDA approved treatment for Pompe disease-an enzyme replacement therapy (ERT)-increases survival of patients, but has unmasked previously unrecognized clinical manifestations of Pompe disease. These clinical signs and symptoms include tracheo-bronchomalacia, vascular aneurysms, and gastro-intestinal discomfort. Together, these previously unrecognized pathologies indicate that GAA-deficiency impacts smooth muscle in addition to skeletal and cardiac muscle. Thus, we sought to characterize smooth muscle pathology in the airway, vascular, gastrointestinal, and genitourinary in the Gaa-/- mouse model. Increased levels of glycogen were present in smooth muscle cells of the aorta, trachea, esophagus, stomach, and bladder of Gaa-/- mice, compared to wild type mice. In addition, there was an increased abundance of both lysosome membrane protein (LAMP1) and autophagosome membrane protein (LC3) indicating vacuolar accumulation in several tissues. Taken together, we show that GAA deficiency results in subsequent pathology in smooth muscle cells, which may lead to life-threatening complications if not properly treated.

Full Text

Duke Authors

Cited Authors

  • McCall, AL; Dhindsa, JS; Bailey, AM; Pucci, LA; Strickland, LM; ElMallah, MK

Published Date

  • 2021

Published In

Volume / Issue

  • 57 / 0

Start / End Page

  • 8 - 18

PubMed ID

  • 33883348

Pubmed Central ID

  • PMC8053439

Electronic International Standard Serial Number (EISSN)

  • 1884-8796

Digital Object Identifier (DOI)

  • 10.1540/jsmr.57.8


  • eng

Conference Location

  • Japan