{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T05:01:25Z","timestamp":1787806885455,"version":"build-2784847793"},"reference-count":32,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T00:00:00Z","timestamp":1661990400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ethan Ikauniks Fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Glycogen storage disease type IX (GSD-IX) constitutes nearly a quarter of all GSDs. This ketotic form of GSD is caused by mutations in phosphorylase kinase (PhK), which is composed of four subunits (\u03b1, \u03b2, \u03b3, \u03b4). PhK is required for the activation of the liver isoform of glycogen phosphorylase (PYGL), which generates free glucose-1-phosphate monomers to be used as energy via cleavage of the \u03b1 -(1,4) glycosidic linkages in glycogen chains. Mutations in any of the PhK subunits can negatively affect the regulatory and catalytic activity of PhK during glycogenolysis. To understand the pathogenesis of GSD-IX-beta, we characterized a newly created PHKB knockout (Phkb\u2212\/\u2212) mouse model. In this study, we assessed fasting blood glucose and ketone levels, serum metabolite concentrations, glycogen phosphorylase activity, and gene expression of gluconeogenic genes and fibrotic genes. Phkb\u2212\/\u2212 mice displayed hepatomegaly with lower fasting blood glucose concentrations. Phkb\u2212\/\u2212 mice showed partial liver glycogen phosphorylase activity and increased sensitivity to pyruvate, indicative of partial glycogenolytic activity and upregulation of gluconeogenesis. Additionally, gene expression analysis demonstrated increased lipid metabolism in Phkb\u2212\/\u2212 mice. Gene expression analysis and liver histology in the livers of old Phkb\u2212\/\u2212 mice (&gt;40 weeks) showed minimal profibrogenic features when analyzed with age-matched wild-type (WT) mice. Collectively, the Phkb\u2212\/\u2212 mouse recapitulates mild clinical features in patients with GSD-IX-beta. Metabolic and molecular analysis confirmed that Phkb\u2212\/\u2212 mice were capable of sustaining energy homeostasis during prolonged fasting by using partial glycogenolysis, increased gluconeogenesis, and potentially fatty acid oxidation in the liver.<\/jats:p>","DOI":"10.3390\/ijms23179944","type":"journal-article","created":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T21:27:17Z","timestamp":1662067637000},"page":"9944","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["A Mouse Model of Glycogen Storage Disease Type IX-Beta: A Role for Phkb in Glycogenolysis"],"prefix":"10.3390","volume":"23","author":[{"given":"Charles J.","family":"Arends","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Connecticut School of Medicine, Farmington, CT 06030, USA"},{"name":"Department of Genetics and Genome Sciences, University of Connecticut Health Center, Farmington, CT 06030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lane H.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Connecticut School of Medicine, Farmington, CT 06030, USA"},{"name":"Gene Therapy Program, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Estrella","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Connecticut School of Medicine, Farmington, CT 06030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9929-6774","authenticated-orcid":false,"given":"Oh Sung","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Kinesiology, University of Connecticut, Storrs, CT 06269, USA"},{"name":"Department of Orthopaedic Surgery and Center on Aging, University of Connecticut Health Center, Farmington, CT 06030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Weinstein","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Connecticut School of Medicine, Farmington, CT 06030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6304-8883","authenticated-orcid":false,"given":"Young Mok","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Connecticut School of Medicine, Farmington, CT 06030, USA"},{"name":"Department of Genetics and Genome Sciences, University of Connecticut Health Center, Farmington, CT 06030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.ymgme.2014.09.005","article-title":"The natural history of glycogen storage disease types VI and IX: Long-term outcome from the largest metabolic center in Canada","volume":"113","author":"Roscher","year":"2014","journal-title":"Mol. 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