A novel mouse model of muscle wasting
Miyake, Masato Tokushima University Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Kuroda, Masashi Tokushima University Tokushima University Educator and Researcher Directory
Kiyonari, Hiroshi RIKEN Center for Life Science Technologies
Takehana, Kenji EA Pharma Co.,Ltd.
Hisanaga, Satoshi Tokushima University
Morimoto, Masatoshi Tokushima University Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Zhang, Jun Tokushima University
Oyadomari, Miho Tokushima University Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Sakaue, Hiroshi Tokushima University Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Formation of 43S and 48S preinitiation complexes plays an important role in muscle protein synthesis. There is no muscle-wasting mouse model caused by a repressed 43S preinitiation complex assembly.
The aim of the present study was to develop a convenient mouse model of skeletal muscle wasting with repressed 43S preinitiation complex assembly.
Material and methods
A ligand-activatable PERK derivative Fv2E-PERK causes the phosphorylation of eukaryotic initiation factor 2α (eIF2α), which inhibits 43S preinitiation complex assembly. Thus, muscle atrophic phenotypes, intracellular signaling pathways, and intracellular free amino acid profiles were investigated in human skeletal muscle α-actin (HSA) promoter-driven Fv2E-PERK transgenic (Tg) mice.
HSA-Fv2E-PERK Tg mice treated with the artificial dimerizer AP20187 phosphorylates eIF2α in skeletal muscles and leads to severe muscle atrophy within a few days of ligand injection. Muscle atrophy was accompanied by a counter regulatory activation of mTORC1 signaling. Moreover, intracellular free amino acid levels were distinctively altered in the skeletal muscles of HSA-Fv2E-PERK Tg mice.
As a novel model of muscle wasting, HSA-Fv2E-PERK Tg mice provide a convenient tool for studying the pathogenesis of muscle loss and for assessing putative therapeutics.
© 2017 Miyake et al. This is an open access article distributed under the terms of the Creative Commons Attribution License( https://creativecommons.org/licenses/by/4.0/ ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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pone_12_6_e0179955.pdf 4.68 MB
Institute of Advanced Medical Sciences