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Sci Rep. 2019 Mar 26;9(1):5116. doi: 10.1038/s41598-019-41414-8.

Low survival rate and muscle fiber-dependent aging effects in the McArdle disease mouse model.

Author information

1
Mitochondrial and Neuromuscular Disorders Unit, Vall d'Hebron Institut de Recerca, Universitat Autònoma de Barcelona, Barcelona, Spain.
2
Sorbonne Université, INSERM UMRS_974, Center of Research in Myology, 75013, Paris, France.
3
Faculty of Sport Sciences, Universidad Europea de Madrid, Madrid, Spain.
4
Mitochondrial and Neuromuscular Diseases Laboratory, 12 de Octubre Hospital Research Institute (i+ 12), Madrid, Spain.
5
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain.
6
Grup de Recerca en Malalties Neuromusculars i Neuropediàtriques, Department of Neurosciences, Institut d'Investigacio en Ciencies de la Salut Germans Trias i Pujol i Campus Can Ruti, Universitat Autònoma de Barcelona, Badalona, Spain.
7
Copenhagen Neuromuscular Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
8
Laboratori de Malalties Neuromusculars, Institut de Recerca Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
9
Mitochondrial and Neuromuscular Disorders Unit, Vall d'Hebron Institut de Recerca, Universitat Autònoma de Barcelona, Barcelona, Spain. tomas.pinos@vhir.org.
10
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain. tomas.pinos@vhir.org.

Abstract

McArdle disease is an autosomal recessive disorder caused by the absence of the muscle glycogen phosphorylase, which leads to impairment of glycogen breakdown. The McArdle mouse, a model heavily affected by glycogen accumulation and exercise intolerance, was used to characterize disease progression at three different ages. The molecular and histopathological consequences of the disease were analyzed in five different hind-limb muscles (soleus, extensor digitorum longus, tibialis anterior, gastrocnemius and quadriceps) of young (8-week-old), adult (35-week-old) and old (70-week-old) mice. We found that McArdle mice have a high perinatal and post-weaning mortality. We also observed a progressive muscle degeneration, fibrosis and inflammation process that was not associated with an increase in muscle glycogen content during aging. Additionally, this progressive degeneration varied among muscle and fiber types. Finally, the lack of glycogen content increase was associated with the inactivation of glycogen synthase and not with compensatory expression of the Pygl and/or Pygb genes in mature muscle.

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