{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T13:58:14Z","timestamp":1791295094041,"version":"4.1.0"},"reference-count":34,"publisher":"The Company of Biologists","issue":"5","license":[{"start":{"date-parts":[[2020,9,3]],"date-time":"2020-09-03T00:00:00Z","timestamp":1599091200000},"content-version":"vor","delay-in-days":1952,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,5,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>McArdle disease, also termed \u2018glycogen storage disease type V\u2019, is a disorder of skeletal muscle carbohydrate metabolism caused by inherited deficiency of the muscle-specific isoform of glycogen phosphorylase (GP-MM). It is an autosomic recessive disorder that is caused by mutations in the PYGM gene and typically presents with exercise intolerance, i.e. episodes of early exertional fatigue frequently accompanied by rhabdomyolysis and myoglobinuria. Muscle biopsies from affected individuals contain subsarcolemmal deposits of glycogen. Besides GP-MM, two other GP isoforms have been described: the liver (GP-LL) and brain (GP-BB) isoforms, which are encoded by the PYGL and PYGB genes, respectively; GP-BB is the main GP isoform found in human and rat foetal tissues, including the muscle, although its postnatal expression is dramatically reduced in the vast majority of differentiated tissues with the exception of brain and heart, where it remains as the major isoform. We developed a cell culture model from knock-in McArdle mice that mimics the glycogen accumulation and GP-MM deficiency observed in skeletal muscle from individuals with McArdle disease. We treated mouse primary skeletal muscle cultures in vitro with sodium valproate (VPA), a histone deacetylase inhibitor. After VPA treatment, myotubes expressed GP-BB and a dose-dependent decrease in glycogen accumulation was also observed. Thus, this in vitro model could be useful for high-throughput screening of new drugs to treat this disease. The immortalization of these primary skeletal muscle cultures could provide a never-ending source of cells for this experimental model. Furthermore, VPA could be considered as a gene-expression modulator, allowing compensatory expression of GP-BB and decreased glycogen accumulation in skeletal muscle of individuals with McArdle disease.<\/jats:p>","DOI":"10.1242\/dmm.020230","type":"journal-article","created":{"date-parts":[[2015,3,12]],"date-time":"2015-03-12T00:43:02Z","timestamp":1426120982000},"page":"467-472","source":"Crossref","is-referenced-by-count":22,"title":["Sodium valproate increases the brain isoform of glycogen phosphorylase: looking for a compensation mechanism in McArdle disease using a mouse primary skeletal-muscle culture<i>in vitro<\/i>"],"prefix":"10.1242","volume":"8","author":[{"given":"Noem\u00ed","family":"de Luna","sequence":"first","affiliation":[{"name":"Mitochondrial Pathology and Neuromuscular Disorders Laboratory, Vall d'Hebron Research Institute, Universitat Aut\u00f2noma de Barcelona, Barcelona 08035, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), Madrid 28029, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Astrid","family":"Brull","sequence":"additional","affiliation":[{"name":"Mitochondrial Pathology and Neuromuscular Disorders Laboratory, Vall d'Hebron Research Institute, Universitat Aut\u00f2noma de Barcelona, Barcelona 08035, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), Madrid 28029, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josep Maria","family":"Guiu","sequence":"additional","affiliation":[{"name":"Mitochondrial Pathology and Neuromuscular Disorders Laboratory, Vall d'Hebron Research Institute, Universitat Aut\u00f2noma de Barcelona, Barcelona 08035, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), Madrid 28029, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Lucia","sequence":"additional","affiliation":[{"name":"Universidad Europea, Madrid 28670, Spain"},{"name":"Instituto de Investigaci\u00f3n \u2018i+12\u2019, Madrid 28041, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel Angel","family":"Martin","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n \u2018i+12\u2019, Madrid 28041, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joaquin","family":"Arenas","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n \u2018i+12\u2019, Madrid 28041, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramon","family":"Mart\u00ed","sequence":"additional","affiliation":[{"name":"Mitochondrial Pathology and Neuromuscular Disorders Laboratory, Vall d'Hebron Research Institute, Universitat Aut\u00f2noma de Barcelona, Barcelona 08035, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), Madrid 28029, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoni L.","family":"Andreu","sequence":"additional","affiliation":[{"name":"Mitochondrial Pathology and Neuromuscular Disorders Laboratory, Vall d'Hebron Research Institute, Universitat Aut\u00f2noma de Barcelona, Barcelona 08035, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), Madrid 28029, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom\u00e0s","family":"Pin\u00f3s","sequence":"additional","affiliation":[{"name":"Mitochondrial Pathology and Neuromuscular Disorders Laboratory, Vall d'Hebron Research Institute, Universitat Aut\u00f2noma de Barcelona, Barcelona 08035, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), Madrid 28029, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021052800081992500_DMM020230C1","doi-asserted-by":"publisher","first-page":"1327","DOI":"10.1046\/j.1471-4159.2000.0721327.x","article-title":"The mood-stabilizing agent valproate inhibits the activity of glycogen synthase kinase-3","volume":"72","author":"Chen","year":"2000","journal-title":"J. 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