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The MyoRobot technology discloses a premature biomechanical decay of skeletal muscle fiber bundles derived from R349P desminopathy mice
Mutations in the Des gene coding for the muscle-specific intermediate filament protein desmin lead to myopathies and cardiomyopathies. We previously generated a R349P desmin knock-in mouse strain as a patient-mimicking model for the corresponding most frequent human desmin mutation R350P. Since noth...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6656739/ https://www.ncbi.nlm.nih.gov/pubmed/31341183 http://dx.doi.org/10.1038/s41598-019-46723-6 |
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author | Haug, Michael Meyer, Charlotte Reischl, Barbara Prölß, Gerhard Vetter, Kristina Iberl, Julian Nübler, Stefanie Schürmann, Sebastian Rupitsch, Stefan J. Heckel, Michael Pöschel, Thorsten Winter, Lilli Herrmann, Harald Clemen, Christoph S. Schröder, Rolf Friedrich, Oliver |
author_facet | Haug, Michael Meyer, Charlotte Reischl, Barbara Prölß, Gerhard Vetter, Kristina Iberl, Julian Nübler, Stefanie Schürmann, Sebastian Rupitsch, Stefan J. Heckel, Michael Pöschel, Thorsten Winter, Lilli Herrmann, Harald Clemen, Christoph S. Schröder, Rolf Friedrich, Oliver |
author_sort | Haug, Michael |
collection | PubMed |
description | Mutations in the Des gene coding for the muscle-specific intermediate filament protein desmin lead to myopathies and cardiomyopathies. We previously generated a R349P desmin knock-in mouse strain as a patient-mimicking model for the corresponding most frequent human desmin mutation R350P. Since nothing is known about the age-dependent changes in the biomechanics of affected muscles, we investigated the passive and active biomechanics of small fiber bundles from young (17–23 wks), adult (25–45 wks) and aged (>60 wks) heterozygous and homozygous R349P desmin knock-in mice in comparison to wild-type littermates. We used a novel automated biomechatronics platform, the MyoRobot, to perform coherent quantitative recordings of passive (resting length-tension curves, visco-elasticity) and active (caffeine-induced force transients, pCa-force, ‘slack-tests’) parameters to determine age-dependent effects of the R349P desmin mutation in slow-twitch soleus and fast-twitch extensor digitorum longus small fiber bundles. We demonstrate that active force properties are not affected by this mutation while passive steady-state elasticity is vastly altered in R349P desmin fiber bundles compatible with a pre-aged phenotype exhibiting stiffer muscle preparations. Visco-elasticity on the other hand, was not altered. Our study represents the first systematic age-related characterization of small muscle fiber bundle preparation biomechanics in conjunction with inherited desminopathy. |
format | Online Article Text |
id | pubmed-6656739 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-66567392019-07-29 The MyoRobot technology discloses a premature biomechanical decay of skeletal muscle fiber bundles derived from R349P desminopathy mice Haug, Michael Meyer, Charlotte Reischl, Barbara Prölß, Gerhard Vetter, Kristina Iberl, Julian Nübler, Stefanie Schürmann, Sebastian Rupitsch, Stefan J. Heckel, Michael Pöschel, Thorsten Winter, Lilli Herrmann, Harald Clemen, Christoph S. Schröder, Rolf Friedrich, Oliver Sci Rep Article Mutations in the Des gene coding for the muscle-specific intermediate filament protein desmin lead to myopathies and cardiomyopathies. We previously generated a R349P desmin knock-in mouse strain as a patient-mimicking model for the corresponding most frequent human desmin mutation R350P. Since nothing is known about the age-dependent changes in the biomechanics of affected muscles, we investigated the passive and active biomechanics of small fiber bundles from young (17–23 wks), adult (25–45 wks) and aged (>60 wks) heterozygous and homozygous R349P desmin knock-in mice in comparison to wild-type littermates. We used a novel automated biomechatronics platform, the MyoRobot, to perform coherent quantitative recordings of passive (resting length-tension curves, visco-elasticity) and active (caffeine-induced force transients, pCa-force, ‘slack-tests’) parameters to determine age-dependent effects of the R349P desmin mutation in slow-twitch soleus and fast-twitch extensor digitorum longus small fiber bundles. We demonstrate that active force properties are not affected by this mutation while passive steady-state elasticity is vastly altered in R349P desmin fiber bundles compatible with a pre-aged phenotype exhibiting stiffer muscle preparations. Visco-elasticity on the other hand, was not altered. Our study represents the first systematic age-related characterization of small muscle fiber bundle preparation biomechanics in conjunction with inherited desminopathy. Nature Publishing Group UK 2019-07-24 /pmc/articles/PMC6656739/ /pubmed/31341183 http://dx.doi.org/10.1038/s41598-019-46723-6 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Haug, Michael Meyer, Charlotte Reischl, Barbara Prölß, Gerhard Vetter, Kristina Iberl, Julian Nübler, Stefanie Schürmann, Sebastian Rupitsch, Stefan J. Heckel, Michael Pöschel, Thorsten Winter, Lilli Herrmann, Harald Clemen, Christoph S. Schröder, Rolf Friedrich, Oliver The MyoRobot technology discloses a premature biomechanical decay of skeletal muscle fiber bundles derived from R349P desminopathy mice |
title | The MyoRobot technology discloses a premature biomechanical decay of skeletal muscle fiber bundles derived from R349P desminopathy mice |
title_full | The MyoRobot technology discloses a premature biomechanical decay of skeletal muscle fiber bundles derived from R349P desminopathy mice |
title_fullStr | The MyoRobot technology discloses a premature biomechanical decay of skeletal muscle fiber bundles derived from R349P desminopathy mice |
title_full_unstemmed | The MyoRobot technology discloses a premature biomechanical decay of skeletal muscle fiber bundles derived from R349P desminopathy mice |
title_short | The MyoRobot technology discloses a premature biomechanical decay of skeletal muscle fiber bundles derived from R349P desminopathy mice |
title_sort | myorobot technology discloses a premature biomechanical decay of skeletal muscle fiber bundles derived from r349p desminopathy mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6656739/ https://www.ncbi.nlm.nih.gov/pubmed/31341183 http://dx.doi.org/10.1038/s41598-019-46723-6 |
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