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

Alberto Real-Martinez; Astrid Brull; Jordi Huerta; Guillermo Tarrasó; Alejandro Lucia; Miguel Angel Martin; Joaquin Arenas; Antoni L Andreu; Gisela Nogales-Gadea; John Vissing; Thomas O. Krag; Noemi de Luna; Tomàs Pinós

doi:10.1038/s41598-019-41414-8

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

Alberto Real-Martinez, Astrid Brull, Jordi Huerta, Guillermo Tarrasó, Alejandro Lucia, Miguel Angel Martin, Joaquin Arenas, Antoni L Andreu, Gisela Nogales-Gadea, John Vissing, Thomas O. Krag, Noemi de Luna, Tomàs Pinós

Institut for Klinisk Medicin

4 Citationer (Scopus)

2 Downloads (Pure)

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.

Originalsprog	Engelsk
Artikelnummer	5116
Tidsskrift	Scientific Reports
Vol/bind	9
Udgave nummer	1
Antal sider	14
ISSN	2045-2322
DOI	https://doi.org/10.1038/s41598-019-41414-8
Status	Udgivet - 1 dec. 2019

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10.1038/s41598-019-41414-8Licens: CC BY

Low survival rate and muscle fiberdependent aging effects in the McArdle disease mouse modelForlagets udgivne version, 3,93 MBLicens: CC BY

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title = "Low survival rate and muscle fiber-dependent aging effects in the McArdle disease mouse model",

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.",

author = "Alberto Real-Martinez and Astrid Brull and Jordi Huerta and Guillermo Tarras{\'o} and Alejandro Lucia and Martin, {Miguel Angel} and Joaquin Arenas and Andreu, {Antoni L} and Gisela Nogales-Gadea and John Vissing and Krag, {Thomas O.} and {de Luna}, Noemi and Tom{\`a}s Pin{\'o}s",

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T1 - Low survival rate and muscle fiber-dependent aging effects in the McArdle disease mouse model

AU - Real-Martinez, Alberto

AU - Brull, Astrid

AU - Huerta, Jordi

AU - Tarrasó, Guillermo

AU - Lucia, Alejandro

AU - Martin, Miguel Angel

AU - Arenas, Joaquin

AU - Andreu, Antoni L

AU - Nogales-Gadea, Gisela

AU - Vissing, John

AU - Krag, Thomas O.

AU - de Luna, Noemi

AU - Pinós, Tomàs

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

AB - 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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DO - 10.1038/s41598-019-41414-8

M3 - Journal article

C2 - 30914683

SN - 2045-2322

VL - 9

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 5116

ER -

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

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