Mice expressing L345P mutant desmin exhibit morphological and functional changes of skeletal and cardiac mitochondria

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...

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Bibliographic Details
Published in:Journal of muscle research and cell motility 2008, Vol.29 (1), p.25-36
Main Authors: Kostareva, Anna, Sjöberg, Gunnar, Bruton, Joseph, Zhang, Shi-Jin, Balogh, Johanna, Gudkova, Alexandra, Hedberg, Birgitta, Edström, Lars, Westerblad, Håkan, Sejersen, Thomas
Format: Article
Language:English
Subjects:
Animal Anatomy
Animals
Basic Medicine
Biomedical and Life Sciences
Biomedicine
calcium
Calcium - metabolism
Cell Biology
desmin
Desmin - genetics
Desmin - metabolism
Echocardiography
Heart
Heart Ventricles - diagnostic imaging
Histology
Life Sciences
Medical and Health Sciences
Medicin och hälsovetenskap
Medicinska och farmaceutiska grundvetenskaper
Mice
Mice, Transgenic
mitochondria
Mitochondria, Heart - metabolism
Mitochondria, Heart - ultrastructure
Mitochondria, Muscle - metabolism
Mitochondria, Muscle - ultrastructure
Mitochondrial Swelling
Morphology
muscle
Muscle Contraction
Muscle Strength
Muscle, Skeletal - physiology
Mutation
Myocardium - metabolism
Myocardium - ultrastructure
Original Paper
Proteomics
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Description
Summary: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 Ca 2+ 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.
ISSN:0142-4319
1573-2657
DOI:10.1007/s10974-008-9139-8