In vivo elongation of thin filaments results in heart failure.
A novel cardiac-specific transgenic mouse model was generated to identify the physiological consequences of elongated thin filaments during post-natal development in the heart. Remarkably, increasing the expression levels in vivo of just one sarcomeric protein, Lmod2, results in ~10% longer thin fil...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2020-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0226138 |
| _version_ | 1818406109266837504 |
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| author | Lei Mi-Mi Gerrie P Farman Rachel M Mayfield Joshua Strom Miensheng Chu Christopher T Pappas Carol C Gregorio |
| author_facet | Lei Mi-Mi Gerrie P Farman Rachel M Mayfield Joshua Strom Miensheng Chu Christopher T Pappas Carol C Gregorio |
| author_sort | Lei Mi-Mi |
| collection | DOAJ |
| description | A novel cardiac-specific transgenic mouse model was generated to identify the physiological consequences of elongated thin filaments during post-natal development in the heart. Remarkably, increasing the expression levels in vivo of just one sarcomeric protein, Lmod2, results in ~10% longer thin filaments (up to 26% longer in some individual sarcomeres) that produce up to 50% less contractile force. Increasing the levels of Lmod2 in vivo (Lmod2-TG) also allows us to probe the contribution of Lmod2 in the progression of cardiac myopathy because Lmod2-TG mice present with a unique cardiomyopathy involving enlarged atrial and ventricular lumens, increased heart mass, disorganized myofibrils and eventually, heart failure. Turning off of Lmod2 transgene expression at postnatal day 3 successfully prevents thin filament elongation, as well as gross morphological and functional disease progression. We show here that Lmod2 has an essential role in regulating cardiac contractile force and function. |
| first_indexed | 2024-12-14T09:06:43Z |
| format | Article |
| id | doaj.art-2d90ecf9462448239a0553f27833ccd2 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-14T09:06:43Z |
| publishDate | 2020-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-2d90ecf9462448239a0553f27833ccd22022-12-21T23:08:41ZengPublic Library of Science (PLoS)PLoS ONE1932-62032020-01-01151e022613810.1371/journal.pone.0226138In vivo elongation of thin filaments results in heart failure.Lei Mi-MiGerrie P FarmanRachel M MayfieldJoshua StromMiensheng ChuChristopher T PappasCarol C GregorioA novel cardiac-specific transgenic mouse model was generated to identify the physiological consequences of elongated thin filaments during post-natal development in the heart. Remarkably, increasing the expression levels in vivo of just one sarcomeric protein, Lmod2, results in ~10% longer thin filaments (up to 26% longer in some individual sarcomeres) that produce up to 50% less contractile force. Increasing the levels of Lmod2 in vivo (Lmod2-TG) also allows us to probe the contribution of Lmod2 in the progression of cardiac myopathy because Lmod2-TG mice present with a unique cardiomyopathy involving enlarged atrial and ventricular lumens, increased heart mass, disorganized myofibrils and eventually, heart failure. Turning off of Lmod2 transgene expression at postnatal day 3 successfully prevents thin filament elongation, as well as gross morphological and functional disease progression. We show here that Lmod2 has an essential role in regulating cardiac contractile force and function.https://doi.org/10.1371/journal.pone.0226138 |
| spellingShingle | Lei Mi-Mi Gerrie P Farman Rachel M Mayfield Joshua Strom Miensheng Chu Christopher T Pappas Carol C Gregorio In vivo elongation of thin filaments results in heart failure. PLoS ONE |
| title | In vivo elongation of thin filaments results in heart failure. |
| title_full | In vivo elongation of thin filaments results in heart failure. |
| title_fullStr | In vivo elongation of thin filaments results in heart failure. |
| title_full_unstemmed | In vivo elongation of thin filaments results in heart failure. |
| title_short | In vivo elongation of thin filaments results in heart failure. |
| title_sort | in vivo elongation of thin filaments results in heart failure |
| url | https://doi.org/10.1371/journal.pone.0226138 |
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