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PXD013294

PXD013294 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleProteomics analysis of 3 months induced RAmKO mice muscle
DescriptionMaintaining skeletal muscle mass is of high importance as muscle atrophy like during sarcopenia or cachexia lead to a decrease in independence and a higher risk of morbidity and mortality. A leading compound in the treatment against ageing and cancer is rapamycin, an inhibitor of mechanistic target of rapamycin complex 1 (mTORC1). Whether the treatment with mTORC1 inhibitors would work at a cost of losing muscle mass is unclear, as most studies have been focusing on the role of mTORC1 specifically during hypertrophy. In order to answer this question we developed an inducible muscle specific knockout mouse model in which raptor can be ablated during adulthood to eliminate mTORC1 activity. We analysed the muscles after different time points and found that after 3 months the mice showed a fiber shift towards slower fiber types, a loss in oxidative capacity but only very few myopathic features. After 5 months the myopathic features became more apparent, however it did not largely affect the ex vivo muscle force. Surprisingly despite the myopathy we did not see a significant loss of muscle mass even after 5 months, that we hypothesised based on mTORC1s central role in protein synthesis. We assume that the myopathy after long-term mTORC1 inactivation is mostly a result of secondary effects through the loss of mitochondria, alterations in metabolism and in cytoskeletal components. In conclusion, during skeletal muscle maintenance mTORC1 is more essential for metabolic processes than it is for maintaining basal muscle mass.Maintaining skeletal muscle mass is of high importance as muscle atrophy like during sarcopenia or cachexia lead to a decrease in independence and a higher risk of morbidity and mortality. A leading compound in the treatment against ageing and cancer is rapamycin, an inhibitor of mechanistic target of rapamycin complex 1 (mTORC1). Whether the treatment with mTORC1 inhibitors would work at a cost of losing muscle mass is unclear, as most studies have been focusing on the role of mTORC1 specifically during hypertrophy. In order to answer this question we developed an inducible muscle specific knockout mouse model in which raptor can be ablated during adulthood to eliminate mTORC1 activity. We analysed the muscles after different time points and found that after 3 months the mice showed a fiber shift towards slower fiber types, a loss in oxidative capacity but only very few myopathic features. After 5 months the myopathic features became more apparent, however it did not largely affect the ex vivo muscle force. Surprisingly despite the myopathy we did not see a significant loss of muscle mass even after 5 months, that we hypothesised based on mTORC1s central role in protein synthesis. We assume that the myopathy after long-term mTORC1 inactivation is mostly a result of secondary effects through the loss of mitochondria, alterations in metabolism and in cytoskeletal components. In conclusion, during skeletal muscle maintenance mTORC1 is more essential for metabolic processes than it is for maintaining basal muscle mass.
HostingRepositoryPRIDE
AnnounceDate2019-10-14
AnnouncementXMLSubmission_2019-10-14_08:33:09.xml
DigitalObjectIdentifierhttps://dx.doi.org/10.6019/PXD013294
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterAlexander Schmidt
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListOxidation; Acetyl; Carbamidomethyl
InstrumentLTQ Orbitrap Elite
Dataset History
RevisionDatetimeStatusChangeLog Entry
02019-03-29 00:33:14ID requested
12019-10-14 08:33:10announced
Publication List
Dataset with its publication pending
Keyword List
curator keyword: Biological
submitter keyword: mTORC1, rapamycin, muscle, mus musculus
Contact List
Alexander Schmidt
contact affiliationBiozentrum, University of Basel, CH-4056 Basel, Switzerland
contact emailalex.schmidt@unibas.ch
lab head
Alexander Schmidt
contact affiliationProteomics Core Facility
contact emailalex.schmidt@unibas.ch
dataset submitter
Full Dataset Link List
Dataset FTP location
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