Triadin deletion induces impaired skeletal muscle function. - Archive ouverte HAL Access content directly
Journal Articles Journal of Biological Chemistry Year : 2009

Triadin deletion induces impaired skeletal muscle function.

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Abstract

Triadin is a multiple proteins family, some isoforms being involved in muscle excitation-contraction coupling, and some having still unknown functions. To obtain clues on triadin functions, we engineered a triadin knock-out mouse line and characterized the physiological effect of triadin ablation on skeletal muscle function. These mice presented a reduced muscle strength, which seemed not to alter their survival and has been characterized in the present work. We first checked in these mice the expression level of the different proteins involved in calcium homeostasis and observed in fast muscles an increase in expression of dihydropyridine receptor, with a large reduction in calsequestrin expression. Electron microscopy analysis of KO muscles morphology demonstrated the presence of triads in abnormal orientation and a reduction in the sarcoplasmic reticulum terminal cisternae volume. Using calcium imaging on cultured myotubes, we observed a reduction in the total amount of calcium stored in the sarcoplasmic reticulum. Physiological studies have been performed to evaluate the influence of triadin deletion on skeletal muscle function. Muscle strength has been measured both on the whole animal model, using hang test or electrical stimulation combined with NMR analysis and strength measurement, or on isolated muscle using electrical stimulation. All the results obtained demonstrate an important reduction in muscle strength, indicating that triadin plays an essential role in skeletal muscle function and in skeletal muscle structure. These results indicate that triadin alteration leads to the development of a myopathy, which could be studied using this new animal model.
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Dates and versions

inserm-00516073 , version 1 (10-12-2010)

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Sarah Oddoux, Julie Brocard, Annie Schweitzer, Peter Szentesi, Benoit Giannesini, et al.. Triadin deletion induces impaired skeletal muscle function.. Journal of Biological Chemistry, 2009, 284 (50), pp.34918-29. ⟨10.1074/jbc.M109.022442⟩. ⟨inserm-00516073⟩
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