Silencing of the Ca2+ Channel ORAI1 Improves the Multi-Systemic Phenotype of Tubular Aggregate Myopathy (TAM) and Stormorken Syndrome (STRMK) in Mice
Abstract
:1. Introduction
2. Results
2.1. Normalized Birth Ratio, and Improved Body Size and Weight Gain of Stim1R304W/+Orai1+/− Mice
2.2. Improved Bone Architecture in Stim1R304W/+Orai1+/− Mice
2.3. Unchanged Skin, Spleen, and Platelet Phenotypes in Stim1R304W/+Orai1+/− Mice
2.4. Improved Muscle Contraction Properties in Stim1R304W/+Orai1+/− Mice
2.5. Normalized Muscle Fiber Size and Improved Autophagy Markers in Stim1R304W/+Orai1+/− Mice
2.6. shRNA-Driven Orai1 Silencing Partially Reverses the Muscle Phenotype of Stim1R304W/+ Mice
3. Discussion
3.1. ORAI1 as the Main Target to Treat the Multi-Systemic TAM/STRMK Phenotype
3.2. Orai1 Downregulation Improves Several but Not All Multi-Systemic TAM/STRMK Phenotype
3.3. shRNA-Mediated Silencing of Orai1 Partially Improved Muscle Function
3.4. Concluding Remarks
4. Materials and Methods
4.1. Animals
4.2. Hanging and Open Field Tests
4.3. In Situ Muscle Force
4.4. Micro-Computerized Bone Tomography (µCT)
4.5. Bleeding Test and Blood Counts
4.6. Muscle, Spleen, and Skin Histology
4.7. Gene Expression and Protein Studies
4.8. shRNA Cloning and AAV Production
4.9. shRNA Screening and Intramuscular AAV Injection
4.10. Study Randomization and Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Silva-Rojas, R.; Pérez-Guàrdia, L.; Lafabrie, E.; Moulaert, D.; Laporte, J.; Böhm, J. Silencing of the Ca2+ Channel ORAI1 Improves the Multi-Systemic Phenotype of Tubular Aggregate Myopathy (TAM) and Stormorken Syndrome (STRMK) in Mice. Int. J. Mol. Sci. 2022, 23, 6968. https://doi.org/10.3390/ijms23136968
Silva-Rojas R, Pérez-Guàrdia L, Lafabrie E, Moulaert D, Laporte J, Böhm J. Silencing of the Ca2+ Channel ORAI1 Improves the Multi-Systemic Phenotype of Tubular Aggregate Myopathy (TAM) and Stormorken Syndrome (STRMK) in Mice. International Journal of Molecular Sciences. 2022; 23(13):6968. https://doi.org/10.3390/ijms23136968
Chicago/Turabian StyleSilva-Rojas, Roberto, Laura Pérez-Guàrdia, Emma Lafabrie, David Moulaert, Jocelyn Laporte, and Johann Böhm. 2022. "Silencing of the Ca2+ Channel ORAI1 Improves the Multi-Systemic Phenotype of Tubular Aggregate Myopathy (TAM) and Stormorken Syndrome (STRMK) in Mice" International Journal of Molecular Sciences 23, no. 13: 6968. https://doi.org/10.3390/ijms23136968