| First Author | Wilson LH | Year | 2019 |
| Journal | Hepatol Commun | Volume | 3 |
| Issue | 11 | Pages | 1544-1555 |
| PubMed ID | 31701076 | Mgi Jnum | J:284765 |
| Mgi Id | MGI:6392116 | Doi | 10.1002/hep4.1426 |
| Citation | Wilson LH, et al. (2019) Liver Glycogen Phosphorylase Deficiency Leads to Profibrogenic Phenotype in a Murine Model of Glycogen Storage Disease Type VI. Hepatol Commun 3(11):1544-1555 |
| abstractText | Mutations in the liver glycogen phosphorylase (Pygl) gene are associated with the diagnosis of glycogen storage disease type VI (GSD-VI). To understand the pathogenesis of GSD-VI, we generated a mouse model with Pygl deficiency (Pygl (-/-)). Pygl (-/-) mice exhibit hepatomegaly, excessive hepatic glycogen accumulation, and low hepatic free glucose along with lower fasting blood glucose levels and elevated blood ketone bodies. Hepatic glycogen accumulation in Pygl (-/-) mice increases with age. Masson's trichrome and picrosirius red staining revealed minimal to mild collagen deposition in periportal, subcapsular, and/or perisinusoidal areas in the livers of old Pygl (-/-) mice (>40 weeks). Consistently, immunohistochemical analysis showed the number of cells positive for alpha smooth muscle actin (alpha-SMA), a marker of activated hepatic stellate cells, was increased in the livers of old Pygl (-/-) mice compared with those of age-matched wild-type (WT) mice. Furthermore, old Pygl (-/-) mice had inflammatory infiltrates associated with hepatic vessels in their livers along with up-regulated hepatic messenger RNA levels of C-C chemokine ligand 5 (Ccl5/Rantes) and monocyte chemoattractant protein 1 (Mcp-1), indicating inflammation, while age-matched WT mice did not. Serum levels of aspartate aminotransferase and alanine aminotransferase were elevated in old Pygl (-/-) mice, indicating liver damage. Conclusion: Pygl deficiency results in progressive accumulation of hepatic glycogen with age and liver damage, inflammation, and collagen deposition, which can increase the risk of liver fibrosis. Collectively, the Pygl-deficient mouse recapitulates clinical features in patients with GSD-VI and provides a model to elucidate the mechanisms underlying hepatic complications associated with defective glycogen metabolism. |
