{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T01:04:24Z","timestamp":1778893464925,"version":"3.51.4"},"reference-count":36,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2015,5,18]],"date-time":"2015-05-18T00:00:00Z","timestamp":1431907200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Fondo de Investigaciones Sanitarias","award":["PI13\/00855, PI12\/00914, PI14\/00903"],"award-info":[{"award-number":["PI13\/00855, PI12\/00914, PI14\/00903"]}]},{"name":"Fondos FEDER"},{"name":"FIS","award":["ISCIII FI11\/00709"],"award-info":[{"award-number":["ISCIII FI11\/00709"]}]},{"name":"Sara Borrell","award":["ISCIII CD11\/00060"],"award-info":[{"award-number":["ISCIII CD11\/00060"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2015,6,15]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>This is the first study to analyse the effect of muscle glycogen phosphorylase depletion in metabolically different muscle types.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In McArdle mice, muscle glycogen phosphorylase is absent in both oxidative and glycolytic muscles.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In McArdle mice, the glycogen debranching enzyme (catabolic) is increased in oxidative muscles, whereas the glycogen branching enzyme (anabolic) is increased in glycolytic muscles.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In McArdle mice, total glycogen synthase is decreased in both oxidative and glycolytic muscles, whereas the phosphorylated inactive form of the enzyme is increased in both oxidative and glycolytic enzymes.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In McArdle mice, glycogen content is higher in glycolytic muscles than in oxidative muscles. Additionally, in all muscles analysed, the glycogen content is higher in males than in females.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The maximal endurance capacity of the McArdle mice is significantly lower compared to heterozygous and wild\u2010type mice.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>McArdle disease, caused by inherited deficiency of the enzyme muscle glycogen phosphorylase (GP\u2010MM), is arguably the paradigm of exercise intolerance. The recent knock\u2010in (p<jats:italic>.R50X\/p.R50X<\/jats:italic>) mouse disease model allows an investigation of the phenotypic consequences of muscle glycogen unavailability and the physiopathology of exercise intolerance. We analysed, in 2\u2010month\u2010old mice [wild\u2010type (<jats:italic>wt\/wt<\/jats:italic>), heterozygous (<jats:italic>p.R50X\/wt<\/jats:italic>) and <jats:italic>p.R50X\/p.R50X<\/jats:italic>)], maximal endurance exercise capacity and the molecular consequences of an absence of GP\u2010MM in the main glycogen metabolism regulatory enzymes: glycogen synthase, glycogen branching enzyme and glycogen debranching enzyme, as well as glycogen content in slow\u2010twitch (<jats:italic>soleus<\/jats:italic>), intermediate (<jats:italic>gastrocnemius<\/jats:italic>) and glycolytic\/fast\u2010twitch (<jats:italic>extensor digitorum longus<\/jats:italic>; <jats:italic>EDL<\/jats:italic>) muscles. Compared with <jats:italic>wt\/wt<\/jats:italic>, exercise capacity (measured in a treadmill test) was impaired in <jats:italic>p.R50X\/p.R50X<\/jats:italic> (\u223c48%) and <jats:italic>p.R50X\/wt<\/jats:italic> mice (\u223c18%). <jats:italic>p.R50X\/p.R50X<\/jats:italic> mice showed an absence of GP\u2010MM in the three muscles. GP\u2010MM was reduced in <jats:italic>p.R50X\/wt<\/jats:italic> mice, especially in the <jats:italic>soleus<\/jats:italic>, suggesting that the function of \u2018slow\u2010twitch\u2019 muscles is less dependent on glycogen catabolism. <jats:italic>p.R50X\/p.R50X<\/jats:italic> mice showed increased glycogen debranching enzyme in the <jats:italic>soleus<\/jats:italic>, increased glycogen branching enzyme in the <jats:italic>gastrocnemius<\/jats:italic> and <jats:italic>EDL<\/jats:italic>, as well as reduced levels of mucle glycogen synthase protein in the three muscles (mean \u223c70%), reflecting a protective mechanism for preventing deleterious glycogen accumulation. Additionally, glycogen content was highest in the <jats:italic>EDL<\/jats:italic> of <jats:italic>p.R50X\/p.R50X<\/jats:italic> mice. Amongst other findings, the present study shows that the expression of the main muscle glycogen regulatory enzymes differs depending on the muscle phenotype (slow\u2010 <jats:italic>vs<\/jats:italic>. fast\u2010twitch) and that even partial GP\u2010MM deficiency affects maximal endurance capacity. Our knock\u2010in model might help to provide insights into the importance of glycogen on muscle function.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp270085","type":"journal-article","created":{"date-parts":[[2015,4,15]],"date-time":"2015-04-15T06:10:32Z","timestamp":1429078232000},"page":"2693-2706","source":"Crossref","is-referenced-by-count":19,"title":["Phenotype consequences of myophosphorylase dysfunction: insights from the McArdle mouse model"],"prefix":"10.1113","volume":"593","author":[{"given":"Astrid","family":"Brull","sequence":"first","affiliation":[{"name":"Neuromuscular and Mitochondrial Disorders Laboratory, Vall d'Hebron Research Institute Universitat Aut\u00f2noma de Barcelona  Barcelona Spain"},{"name":"Biomedical Network Research Centre on Rare Diseases (CIBERER) Instituto de Salud Carlos III  Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noem\u00ed","family":"de Luna","sequence":"additional","affiliation":[{"name":"Neuromuscular and Mitochondrial Disorders Laboratory, Vall d'Hebron Research Institute Universitat Aut\u00f2noma de Barcelona  Barcelona Spain"},{"name":"Biomedical Network Research Centre on Rare Diseases (CIBERER) Instituto de Salud Carlos III  Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Albert","family":"Blanco\u2010Grau","sequence":"additional","affiliation":[{"name":"Neuromuscular and Mitochondrial Disorders Laboratory, Vall d'Hebron Research Institute Universitat Aut\u00f2noma de Barcelona  Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alejandro","family":"Lucia","sequence":"additional","affiliation":[{"name":"Universidad Europea  Madrid Spain"},{"name":"Instituto de Investigaci\u00f3n \u2018i+12\u2019  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel Angel","family":"Martin","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n \u2018i+12\u2019  Madrid 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