Mice expressing L345P mutant desmin exhibit morphological and functional changes of skeletal and cardiac mitochondria
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1253668
- author
- Kostareva, Anna ; Sjoberg, Gunnar ; Bruton, Joseph ; Zhang, Shi-Jin ; Balogh, Johanna LU ; Gudkova, Alexandra ; Hedberg, Birgitta ; Edstrom, Lars ; Westerblad, Hakan and Sejersen, Thomas
- organization
- publishing date
- 2008
- 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
- pmid:18563598
- 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
- 2016-04-01 13:28:26
- date last changed
- 2022-03-29 07:41:50
@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}}, keywords = {{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}}, doi = {{10.1007/s10974-008-9139-8}}, volume = {{29}}, year = {{2008}}, }