Phenotype consequences of myophosphorylase dysfunction: insights from the McArdle mouse model

McArdle disease, caused by inherited deficiency of the enzyme muscle glycogen phosphorylase (GP-MM), is arguably the paradigm of exercise intolerance. The recent knock-in (p.R50X/p.R50X) mouse disease model allows an investigation of the phenotypic consequences of muscle glycogen unavailability and...

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Bibliographic Details
Authors: Brull, Astrid, Luna, Noemí de, Blanco-Grau, A, Lucía Mulas, Alejandro, Martín Casanueva, Miguel Ángel, Arenas, Joaquín, Martí, Ramón, Andreu, Antoni L., Pinós, Tomás
Format: article
Publication Date:2015
Country:España
Institution:Universidad Europea (UEM)
Repository:ABACUS. Repositorio de Producción Científica
Language:English
OAI Identifier:oai:abacus.universidadeuropea.com:11268/4007
Online Access:http://hdl.handle.net/11268/4007
Access Level:Open access
Keyword:Knock-in mouse
Glycogen phosphorylase
Muscle phenotype
Enfermedades - McArdle
Ejercicio físico
Genética
Ciencia
Salud
Description
Summary:McArdle disease, caused by inherited deficiency of the enzyme muscle glycogen phosphorylase (GP-MM), is arguably the paradigm of exercise intolerance. The recent knock-in (p.R50X/p.R50X) mouse disease model allows an investigation of the phenotypic consequences of muscle glycogen unavailability and the physiopathology of exercise intolerance. We analysed, in 2-month-old mice [wild-type (wt/wt), heterozygous (p.R50X/wt) and p.R50X/p.R50X)], maximal endurance exercise capacity and the molecular consequences of an absence of GP-MM in the main glycogen metabolism regulatory enzymes: glycogen synthase, glycogen branching enzyme and glycogen debranching enzyme, as well as glycogen content in slow-twitch (soleus), intermediate (gastrocnemius) and glycolytic/fast-twitch (extensor digitorum longus; EDL) muscles.