{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T04:46:42Z","timestamp":1791002802603,"version":"4.1.0"},"reference-count":18,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","license":[{"start":{"date-parts":[[2019,9,24]],"date-time":"2019-09-24T00:00:00Z","timestamp":1569283200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hepatol Commun"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:p>Mutations in the liver glycogen phosphorylase (<jats:italic toggle=\"yes\">Pygl<\/jats:italic>) gene are associated with the diagnosis of glycogen storage disease type VI (GSD\u2010VI). To understand the pathogenesis of GSD\u2010VI, we generated a mouse model with <jats:italic toggle=\"yes\">Pygl<\/jats:italic> deficiency (<jats:italic toggle=\"yes\">Pygl<\/jats:italic>\n                           <jats:sup>\u2212\/\u2212<\/jats:sup>). <jats:italic toggle=\"yes\">Pygl<\/jats:italic>\n                           <jats:sup>\u2212\/\u2212<\/jats:sup> 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 <jats:italic toggle=\"yes\">Pygl<\/jats:italic>\n                           <jats:sup>\u2212\/\u2212<\/jats:sup> 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 <jats:italic toggle=\"yes\">Pygl<\/jats:italic>\n                           <jats:sup>\u2212\/\u2212<\/jats:sup> mice (&gt;40\u00a0weeks). Consistently, immunohistochemical analysis showed the number of cells positive for alpha smooth muscle actin (\u03b1\u2010SMA), a marker of activated hepatic stellate cells, was increased in the livers of old <jats:italic toggle=\"yes\">Pygl<\/jats:italic>\n                           <jats:sup>\u2212\/\u2212<\/jats:sup> mice compared with those of age\u2010matched wild\u2010type (WT) mice. Furthermore, old <jats:italic toggle=\"yes\">Pygl<\/jats:italic>\n                           <jats:sup>\u2212\/\u2212<\/jats:sup> mice had inflammatory infiltrates associated with hepatic vessels in their livers along with up\u2010regulated hepatic messenger RNA levels of C\u2010C chemokine ligand 5 (<jats:italic toggle=\"yes\">Ccl5<\/jats:italic>\/<jats:italic toggle=\"yes\">Rantes<\/jats:italic>) and monocyte chemoattractant protein 1 (<jats:italic toggle=\"yes\">Mcp\u20101<\/jats:italic>), indicating inflammation, while age\u2010matched WT mice did not. Serum levels of aspartate aminotransferase and alanine aminotransferase were elevated in old <jats:italic toggle=\"yes\">Pygl<\/jats:italic>\n                           <jats:sup>\u2212\/\u2212<\/jats:sup> mice, indicating liver damage. <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>: <jats:italic toggle=\"yes\">Pygl<\/jats:italic> 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 <jats:italic toggle=\"yes\">Pygl<\/jats:italic>\u2010deficient mouse recapitulates clinical features in patients with GSD\u2010VI and provides a model to elucidate the mechanisms underlying hepatic complications associated with defective glycogen metabolism.<\/jats:p>","DOI":"10.1002\/hep4.1426","type":"journal-article","created":{"date-parts":[[2019,9,24]],"date-time":"2019-09-24T11:22:07Z","timestamp":1569324127000},"page":"1544-1555","source":"Crossref","is-referenced-by-count":38,"title":["Liver Glycogen Phosphorylase Deficiency Leads to Profibrogenic Phenotype in a Murine Model of Glycogen Storage Disease Type VI"],"prefix":"10.1097","volume":"3","author":[{"given":"Lane H.","family":"Wilson","sequence":"first","affiliation":[{"name":"Glycogen Storage Disease Program,Department of Pediatrics,University of Connecticut School of Medicine,Farmington,CT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun\u2010Ho","family":"Cho","sequence":"additional","affiliation":[{"name":"Glycogen Storage Disease Program,Department of Pediatrics,University of Connecticut School of Medicine,Farmington,CT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Estrella","sequence":"additional","affiliation":[{"name":"Glycogen Storage Disease Program,Department of Pediatrics,University of Connecticut School of Medicine,Farmington,CT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan A.","family":"Smyth","sequence":"additional","affiliation":[{"name":"Connecticut Veterinary Medical Diagnostic Laboratory,Department of Pathobiology and Veterinary Science,University of Connecticut,Storrs,CT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Wu","sequence":"additional","affiliation":[{"name":"Biostatistics Center,Connecticut Convergence Institute for Translation in Regenerative Engineering,University of Connecticut Health Center,Farmington,CT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tayoot","family":"Chengsupanimit","sequence":"additional","affiliation":[{"name":"Glycogen Storage Disease Program,University of Florida College of Medicine,Gainesville,FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurie M.","family":"Brown","sequence":"additional","affiliation":[{"name":"Glycogen Storage Disease Program,University of Florida College of Medicine,Gainesville,FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Weinstein","sequence":"additional","affiliation":[{"name":"Glycogen Storage Disease Program,Department of Pediatrics,University of Connecticut School of Medicine,Farmington,CT"},{"name":"Glycogen Storage Disease Program,Connecticut Children's Medical 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