Ligand-induced rapid skeletal muscle atrophy in HSA-Fv2E-PERK transgenic mice.
Level 5 - mechanism / opinion, no new human data
Animal/bench research with no human data
PubMed 28644884 · doi:10.1371/journal.pone.0179955
What was done
The authors developed and evaluated a transgenic mouse model (HSA-Fv2E-PERK Tg mice) designed to suppress 43S preinitiation complex assembly during muscle protein synthesis. Skeletal muscle-specific Fv2E-PERK was activated using the artificial dimerizer AP20187 to induce eukaryotic initiation factor 2α (eIF2α) phosphorylation. They examined muscle atrophic phenotypes, intracellular signaling pathways (including mTORC1), and intracellular free amino acid profiles following ligand administration.
What was found
Treatment with AP20187 induced eIF2α phosphorylation in skeletal muscles, resulting in severe skeletal muscle atrophy within a few days of injection. The induced atrophy was accompanied by a counter-regulatory activation of mTORC1 signaling and distinct alterations in intracellular free amino acid levels in skeletal muscle. The abstract reported no specific numerical values, effect sizes, or sample sizes.
Why it matters
This study establishes an inducible mouse model of rapid skeletal muscle wasting driven specifically by repressed translation initiation complex assembly. It provides a standardized preclinical system to explore the molecular pathogenesis of muscle loss and screen prospective therapeutics.
Limits
The study was conducted exclusively in a transgenic mouse model, meaning findings cannot be directly applied to human muscle wasting disorders. The abstract provides no quantitative metrics (such as percentage of muscle mass lost, sample sizes, or baseline comparator data) and does not describe functional muscle performance outcomes or long-term reversibility.
Cited by
- supports Phosphorylation of the initiation factor eIF2-alpha impairs the muscle cell's ability to mount a protein synthetic response.