ArticleHuman molecular genetics2014
Enhanced Ca²⁺ influx from STIM1-Orai1 induces muscle pathology in mouse models of muscular dystrophy.
Article in Human molecular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 67 citations in OpenAlex.
- Pathological calcium overload impairs skeletal muscle regeneration through sustained NFAT-dependent proliferative signaling.Experimental & molecular medicine · 2026Article
- Estrogens and Antioxidants Prevent the Formation of Tubular Aggregates in Aging Male Mice.International journal of molecular sciences · 2025Article
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- DWORF expression is reduced in a large animal model of Duchenne muscular dystrophy.Disease models & mechanisms · 2025Article
- Effects of aging on calcium channels in skeletal muscle.Frontiers in molecular biosciences · 2025Review
- Stem/progenitor cell-based therapy for Duchenne muscular dystrophy.Frontiers in cell and developmental biology · 2025Review
- Differential functional role of Orai1 variants in constitutive CaThe Journal of biological chemistry · 2024Article
- Loss of Calpain 3 dysregulates store-operated calcium entry and its exercise response in mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- MCU-independent CaScientific reports · 2024Article
- ORAI1 inhibition as an efficient preclinical therapy for tubular aggregate myopathy and Stormorken syndrome.JCI insight · 2024Article
- Loss of calpain 3 dysregulates store-operated calcium entry and its exercise response in mice.bioRxiv : the preprint server for biology · 2024Article
- SERCA1 Overexpression in Skeletal Muscle Attenuates Muscle Atrophy and Improves Motor Function in a Mouse Model of ALS.Journal of neuromuscular diseases · 2024Article
- Searching for Mechanisms Underlying the Assembly of Calcium Entry Units: The Role of Temperature and pH.International journal of molecular sciences · 2023Article
- Ion Channels of the Sarcolemma and Intracellular Organelles in Duchenne Muscular Dystrophy: A Role in the Dysregulation of Ion Homeostasis and a Possible Target for Therapy.International journal of molecular sciences · 2023Review
- Constitutive assembly of Ca2+ entry units in soleus muscle from calsequestrin knockout mice.The Journal of general physiology · 2022Article
- Proteomic profiling of impaired excitation-contraction coupling and abnormal calcium handling in muscular dystrophy.Proteomics · 2022Review
- Postdevelopmental knockout of Orai1 improves muscle pathology in a mouse model of Duchenne muscular dystrophy.The Journal of general physiology · 2022Article
- Silencing of the CaInternational journal of molecular sciences · 2022Article
- Role of store-operated Ca2+ entry in cardiovascular disease.Cell communication and signaling : CCS · 2022Review
- STIM and Orai Mediated Regulation of Calcium Signaling in Age-Related Diseases.Frontiers in aging · 2022Review
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Muscular dystrophy is a progressive muscle wasting disease that is thought to be initiated by unregulated Ca(2+) influx into myofibers leading to their death. Store-operated Ca(2+) entry (SOCE) through sarcolemmal Ca(2+) selective Orai1 channels in complex with STIM1 in the sarcoplasmic reticulum is one such potential disease mechanism for pathologic Ca(2+) entry. Here, we generated a mouse model of STIM1 overexpression in skeletal muscle to determine whether this type of Ca(2+) entry could induce muscular dystrophy. Myofibers from muscle-specific STIM1 transgenic mice showed a significant increase in SOCE in skeletal muscle, modeling an observed increase in the same current in dystrophic myofibers. Histological and biochemical analysis of STIM1 transgenic mice showed fulminant muscle disease characterized by myofiber necrosis, swollen mitochondria, infiltration of inflammatory cells, enhanced interstitial fibrosis and elevated serum creatine kinase levels. This dystrophic-like disease in STIM1 transgenic mice was abrogated by crossing in a transgene expressing a dominant-negative Orai1 (dnOrai1) mutant. The dnOrai1 transgene also significantly reduced the severity of muscular dystrophy in both mdx (dystrophin mutant mice) and δ-sarcoglycan-deficient (Sgcd(-/-)) mouse models of disease. Hence, Ca(2+) influx across an unstable sarcolemma due to increased activity of a STIM1-Orai1 complex is a disease determinant in muscular dystrophy, and hence, SOCE represents a potential therapeutic target.
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