The TTN p. Tyr4418Ter mutation causes cardiomyopathy in human and mice.
<h4>Objective</h4>To generate a mouse model carrying TTNtv Y4370* simulating the newly discovered human heterozygous nonsense TTNtv c.13254T>G (p.Tyr4418Ter) to supplement and improve the functional evidence of pathogenic mutation TTNtv c.13254T>G on the pathogenic type of dilated...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2024-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0296802&type=printable |
| _version_ | 1797292810161881088 |
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| author | Wenqiang Sun Xiaohui Liu Laichun Song Liang Tao Kaisheng Lai Hui Jiang Hongyan Xiao |
| author_facet | Wenqiang Sun Xiaohui Liu Laichun Song Liang Tao Kaisheng Lai Hui Jiang Hongyan Xiao |
| author_sort | Wenqiang Sun |
| collection | DOAJ |
| description | <h4>Objective</h4>To generate a mouse model carrying TTNtv Y4370* simulating the newly discovered human heterozygous nonsense TTNtv c.13254T>G (p.Tyr4418Ter) to supplement and improve the functional evidence of pathogenic mutation TTNtv c.13254T>G on the pathogenic type of dilated cardiomyopathy.<h4>Methods</h4>We generated 4 mice carrying TTNtv p. Y4370* through CRISPR/Cas-mediated genome engineering. Monthly serological detection, bimonthly echocardiography, and histology evaluation were carried out to observe and compare alterations of cardiac structure and function between 4 TTN+/- mice and 4 wild-type (WT) mice.<h4>Results</h4>For the two-month-old TTN+/- mice, serum glutamic-oxalacetic transaminase (AST), lactic dehydrogenase (LDH), and creatine kinase (CK) were significantly increased, the diastolic Left Ventricular Systolic Anterior Wall (LVAW), and the LV mass markedly rose, with the left ventricular volume displaying an increasing trend and Ejection Fraction (EF) and Fractional Shortening (FS) showing a decreasing trend. Besides, the histological evaluation showed that cardiac fibrosis level and positive rate of cardiac mast cell of TTN+/- mice were obviously increased compared with WT mice.<h4>Conclusions</h4>TTNtv Y4370* could lead to cardiac structure and function alterations in mice, supplementing the evidence of TTNtv c.13254T>G pathogenicity in human. |
| first_indexed | 2024-03-07T20:02:52Z |
| format | Article |
| id | doaj.art-36e2634b6b6944f9b2fda3c2eb57923e |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-03-07T20:02:52Z |
| publishDate | 2024-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-36e2634b6b6944f9b2fda3c2eb57923e2024-02-28T05:31:45ZengPublic Library of Science (PLoS)PLoS ONE1932-62032024-01-01192e029680210.1371/journal.pone.0296802The TTN p. Tyr4418Ter mutation causes cardiomyopathy in human and mice.Wenqiang SunXiaohui LiuLaichun SongLiang TaoKaisheng LaiHui JiangHongyan Xiao<h4>Objective</h4>To generate a mouse model carrying TTNtv Y4370* simulating the newly discovered human heterozygous nonsense TTNtv c.13254T>G (p.Tyr4418Ter) to supplement and improve the functional evidence of pathogenic mutation TTNtv c.13254T>G on the pathogenic type of dilated cardiomyopathy.<h4>Methods</h4>We generated 4 mice carrying TTNtv p. Y4370* through CRISPR/Cas-mediated genome engineering. Monthly serological detection, bimonthly echocardiography, and histology evaluation were carried out to observe and compare alterations of cardiac structure and function between 4 TTN+/- mice and 4 wild-type (WT) mice.<h4>Results</h4>For the two-month-old TTN+/- mice, serum glutamic-oxalacetic transaminase (AST), lactic dehydrogenase (LDH), and creatine kinase (CK) were significantly increased, the diastolic Left Ventricular Systolic Anterior Wall (LVAW), and the LV mass markedly rose, with the left ventricular volume displaying an increasing trend and Ejection Fraction (EF) and Fractional Shortening (FS) showing a decreasing trend. Besides, the histological evaluation showed that cardiac fibrosis level and positive rate of cardiac mast cell of TTN+/- mice were obviously increased compared with WT mice.<h4>Conclusions</h4>TTNtv Y4370* could lead to cardiac structure and function alterations in mice, supplementing the evidence of TTNtv c.13254T>G pathogenicity in human.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0296802&type=printable |
| spellingShingle | Wenqiang Sun Xiaohui Liu Laichun Song Liang Tao Kaisheng Lai Hui Jiang Hongyan Xiao The TTN p. Tyr4418Ter mutation causes cardiomyopathy in human and mice. PLoS ONE |
| title | The TTN p. Tyr4418Ter mutation causes cardiomyopathy in human and mice. |
| title_full | The TTN p. Tyr4418Ter mutation causes cardiomyopathy in human and mice. |
| title_fullStr | The TTN p. Tyr4418Ter mutation causes cardiomyopathy in human and mice. |
| title_full_unstemmed | The TTN p. Tyr4418Ter mutation causes cardiomyopathy in human and mice. |
| title_short | The TTN p. Tyr4418Ter mutation causes cardiomyopathy in human and mice. |
| title_sort | ttn p tyr4418ter mutation causes cardiomyopathy in human and mice |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0296802&type=printable |
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