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

Kostareva, Anna; Sjoberg, Gunnar; Bruton, Joseph; Zhang, Shi-Jin; Balogh, Johanna LU ; Gudkova, Alexandra; Hedberg, Birgitta; Edstrom, Lars; Westerblad, Hakan and Sejersen, Thomas (2008) In Journal of Muscle Research and Cell Motility 29(1). p.25-36
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
calcium, mitochondria, mice, desmin, mutation, muscle
in
Journal of Muscle Research and Cell Motility
volume
29
issue
1
pages
25 - 36
publisher
Springer
external identifiers
  • wos:000257946200003
  • scopus:48349117479
ISSN
0142-4319
DOI
10.1007/s10974-008-9139-8
language
English
LU publication?
yes
id
b44c8748-90c5-4f86-9e6d-3f13dcfb41e4 (old id 1253668)
date added to LUP
2008-11-07 14:50:34
date last changed
2017-04-23 03:51:25
@article{b44c8748-90c5-4f86-9e6d-3f13dcfb41e4,
  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.},
  author       = {Kostareva, Anna and Sjoberg, Gunnar and Bruton, Joseph and Zhang, Shi-Jin and Balogh, Johanna and Gudkova, Alexandra and Hedberg, Birgitta and Edstrom, Lars and Westerblad, Hakan and Sejersen, Thomas},
  issn         = {0142-4319},
  keyword      = {calcium,mitochondria,mice,desmin,mutation,muscle},
  language     = {eng},
  number       = {1},
  pages        = {25--36},
  publisher    = {Springer},
  series       = {Journal of Muscle Research and Cell Motility},
  title        = {Mice expressing L345P mutant desmin exhibit morphological and functional changes of skeletal and cardiac mitochondria},
  url          = {http://dx.doi.org/10.1007/s10974-008-9139-8},
  volume       = {29},
  year         = {2008},
}