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  • Kostareva, Anna, et al. (författare)
  • Mice expressing L345P mutant desmin exhibit morphological and functional changes of skeletal and cardiac mitochondria
  • 2008
  • Ingår i: Journal of Muscle Research and Cell Motility. - : Springer Science and Business Media LLC. - 0142-4319 .- 1573-2657. ; 29:1, s. 25-36
  • Tidskriftsartikel (refereegranskat)abstract
    • Desmin mutations underlie inherited myopathies/cardiomyopathies with varying severity and involvement of the skeletal and cardiac muscles. We developed a transgenic mouse model expressing low level of the L345P desmin mutation (DESMUT mice) in order to uncover changes in skeletal and cardiac muscles caused by this mutation. The most striking ultrastructural changes in muscle from DESMUT mice were mitochondrial swelling and vacuolization. The mitochondrial Ca2+ level was significantly increased in skeletal and cardiac myocytes from DESMUT mice compared to wild type cells during and after contractions. In isolated DESMUT soleus muscles, contractile function and recovery from fatigue were impaired. A SHIRPA screening test for neuromuscular performance demonstrated decreased motor function in DESMUT compared to WT mice. Echocardiographic changes in DESMUT mice included left ventricular wall hypertrophy and a decreased left ventricular chamber dimension. The results imply that low levels of L345P desmin acts, at least partially, by a dominant negative effect on mitochondria.
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