Activity, Motor Control & Coordination
Pain - Thermal Allodynia / Hyperalgesia
Pain - Spontaneous Pain - Postural Deficit
Pain - Mechanical Allodynia / Hyperalgesia
Anxiety & Depression Disorder
Learning/Memory - Attention - Addiction
Physiology & Respiratory Research
Metabolism - Food & Drink Intake
Pain
Central Nervous System (CNS)
Neurodegeneration
Sensory system
Motor control
Mood Disorders
Other disorders
Muscular system
Joints
Metabolism
Cross-disciplinary subjects
Preclinical studies and opioids: role in crisis management in the United States Authors
R Silva-Rojas, S Treves, H Jacobs, P Kessler et al
Lab
Institut de G
Journal
Human Molecular Genetics
Abstract
Strict regulation of Ca2+ homeostasis is essential for normal cellular physiology. Store-operated Ca2+ entry (SOCE) is a major mechanism controlling basal Ca2+ levels and intracellular Ca2+ store refilling, and abnormal SOCE severely impacts on human health. Overactive SOCE results in excessive extracellular Ca2+ entry due to dominant STIM1 or ORAI1 mutations, and has been associated with tubular aggregate myopathy (TAM) and Stormorken syndrome (STRMK). Both disorders are spectra of the same disease and involve muscle weakness, myalgia, and cramps, and additional multi-systemic signs including miosis, bleeding diathesis, hyposplenism, dyslexia, short stature, and ichthyosis. To elucidate the physiological consequences of STIM1 over-activation, we generated a murine model harboring the most common TAM/Stormorken syndrome mutation and characterized the phenotype at the histological, ultrastructural, metabolic, physiological, and functional level. In accordance with the clinical picture of TAM/Stormorken syndrome, the Stim1R304W/+ mice manifested muscle weakness, thrombocytopenia, skin and eye anomalies, and spleen dysfunction, as well as additional features not yet observed in patients such as abnormal bone architecture and immune system dysregulation. The murine muscles exhibited contraction and relaxation defects as well as dystrophic features, and functional investigations unraveled increased Ca2+ influx in myotubes. In conclusion, we provide insight into the pathophysiological effect of the STIM1 R304W mutation in different cells, tissues, and organs, and thereby significantly contribute to a deeper understanding of the pathomechanisms underlying TAM/Stormorken syndrome and other human disorders involving aberrant Ca2+ homeostasis and affecting muscle, bones, platelets, or the immune system.
BIOSEB Instruments Used:
Aron Test or Four Plates Test (LE830),Grip strength test (BIO-GS3),Rotarod (BX-ROD)
