PXD013294 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Proteomics analysis of 3 months induced RAmKO mice muscle |
Description | 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.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. |
HostingRepository | PRIDE |
AnnounceDate | 2019-10-14 |
AnnouncementXML | Submission_2019-10-14_08:33:09.xml |
DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD013294 |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Supported dataset by repository |
PrimarySubmitter | Alexander Schmidt |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | Oxidation; Acetyl; Carbamidomethyl |
Instrument | LTQ Orbitrap Elite |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2019-03-29 00:33:14 | ID requested | |
⏵ 1 | 2019-10-14 08:33:10 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
curator keyword: Biological |
submitter keyword: mTORC1, rapamycin, muscle, mus musculus |
Contact List
Alexander Schmidt |
contact affiliation | Biozentrum, University of Basel, CH-4056 Basel, Switzerland |
contact email | alex.schmidt@unibas.ch |
lab head | |
Alexander Schmidt |
contact affiliation | Proteomics Core Facility |
contact email | alex.schmidt@unibas.ch |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD013294
- Label: PRIDE project
- Name: Proteomics analysis of 3 months induced RAmKO mice muscle