Alterations at the Cross-Bridge Level Are Associated with a Paradoxical Gain of Muscle Function In Vivo in a Mouse Model of Nemaline Myopathy
Nemaline myopathy is the most common disease entity among non-dystrophic skeletal muscle congenital diseases. The first disease causing mutation (Met9Arg) was identified in the gene encoding α-tropomyosinslow gene (TPM3). Considering the conflicting findings of the previous studies on the transgenic...
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| Format: | Online |
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Public Library of Science
2014
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4182639/ |
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pubmed-41826392014-10-07 Alterations at the Cross-Bridge Level Are Associated with a Paradoxical Gain of Muscle Function In Vivo in a Mouse Model of Nemaline Myopathy Gineste, Charlotte Ottenheijm, Coen Le Fur, Yann Banzet, Sébastien Pecchi, Emilie Vilmen, Christophe Cozzone, Patrick J. Koulmann, Nathalie Hardeman, Edna C. Bendahan, David Gondin, Julien Research Article Nemaline myopathy is the most common disease entity among non-dystrophic skeletal muscle congenital diseases. The first disease causing mutation (Met9Arg) was identified in the gene encoding α-tropomyosinslow gene (TPM3). Considering the conflicting findings of the previous studies on the transgenic (Tg) mice carrying the TPM3 Met9Arg mutation, we investigated carefully the effect of the Met9Arg mutation in 8–9 month-old Tg(TPM3)Met9Arg mice on muscle function using a multiscale methodological approach including skinned muscle fibers analysis and in vivo investigations by magnetic resonance imaging and 31-phosphorus magnetic resonance spectroscopy. While in vitro maximal force production was reduced in Tg(TPM3)Met9Arg mice as compared to controls, in vivo measurements revealed an improved mechanical performance in the transgenic mice as compared to the former. The reduced in vitro muscle force might be related to alterations occuring at the cross-bridges level with muscle-specific underlying mechanisms. In vivo muscle improvement was not associated with any changes in either muscle volume or energy metabolism. Our findings indicate that TPM3(Met9Arg) mutation leads to a mild muscle weakness in vitro related to an alteration at the cross-bridges level and a paradoxical gain of muscle function in vivo. These results clearly point out that in vitro alterations are muscle-dependent and do not necessarily translate into similar changes in vivo. Public Library of Science 2014-09-30 /pmc/articles/PMC4182639/ /pubmed/25268244 http://dx.doi.org/10.1371/journal.pone.0109066 Text en © 2014 Gineste et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Gineste, Charlotte Ottenheijm, Coen Le Fur, Yann Banzet, Sébastien Pecchi, Emilie Vilmen, Christophe Cozzone, Patrick J. Koulmann, Nathalie Hardeman, Edna C. Bendahan, David Gondin, Julien |
| spellingShingle |
Gineste, Charlotte Ottenheijm, Coen Le Fur, Yann Banzet, Sébastien Pecchi, Emilie Vilmen, Christophe Cozzone, Patrick J. Koulmann, Nathalie Hardeman, Edna C. Bendahan, David Gondin, Julien Alterations at the Cross-Bridge Level Are Associated with a Paradoxical Gain of Muscle Function In Vivo in a Mouse Model of Nemaline Myopathy |
| author_facet |
Gineste, Charlotte Ottenheijm, Coen Le Fur, Yann Banzet, Sébastien Pecchi, Emilie Vilmen, Christophe Cozzone, Patrick J. Koulmann, Nathalie Hardeman, Edna C. Bendahan, David Gondin, Julien |
| author_sort |
Gineste, Charlotte |
| title |
Alterations at the Cross-Bridge Level Are Associated with a Paradoxical Gain of Muscle Function In Vivo in a Mouse Model of Nemaline Myopathy |
| title_short |
Alterations at the Cross-Bridge Level Are Associated with a Paradoxical Gain of Muscle Function In Vivo in a Mouse Model of Nemaline Myopathy |
| title_full |
Alterations at the Cross-Bridge Level Are Associated with a Paradoxical Gain of Muscle Function In Vivo in a Mouse Model of Nemaline Myopathy |
| title_fullStr |
Alterations at the Cross-Bridge Level Are Associated with a Paradoxical Gain of Muscle Function In Vivo in a Mouse Model of Nemaline Myopathy |
| title_full_unstemmed |
Alterations at the Cross-Bridge Level Are Associated with a Paradoxical Gain of Muscle Function In Vivo in a Mouse Model of Nemaline Myopathy |
| title_sort |
alterations at the cross-bridge level are associated with a paradoxical gain of muscle function in vivo in a mouse model of nemaline myopathy |
| description |
Nemaline myopathy is the most common disease entity among non-dystrophic skeletal muscle congenital diseases. The first disease causing mutation (Met9Arg) was identified in the gene encoding α-tropomyosinslow gene (TPM3). Considering the conflicting findings of the previous studies on the transgenic (Tg) mice carrying the TPM3
Met9Arg mutation, we investigated carefully the effect of the Met9Arg mutation in 8–9 month-old Tg(TPM3)Met9Arg mice on muscle function using a multiscale methodological approach including skinned muscle fibers analysis and in
vivo investigations by magnetic resonance imaging and 31-phosphorus magnetic resonance spectroscopy. While in
vitro maximal force production was reduced in Tg(TPM3)Met9Arg mice as compared to controls, in
vivo measurements revealed an improved mechanical performance in the transgenic mice as compared to the former. The reduced in
vitro muscle force might be related to alterations occuring at the cross-bridges level with muscle-specific underlying mechanisms. In vivo muscle improvement was not associated with any changes in either muscle volume or energy metabolism. Our findings indicate that TPM3(Met9Arg) mutation leads to a mild muscle weakness in
vitro related to an alteration at the cross-bridges level and a paradoxical gain of muscle function in
vivo. These results clearly point out that in
vitro alterations are muscle-dependent and do not necessarily translate into similar changes in
vivo.
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| publisher |
Public Library of Science |
| publishDate |
2014 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4182639/ |
| _version_ |
1613140005248565248 |