{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T12:47:57Z","timestamp":1755694077360,"version":"3.40.5"},"reference-count":24,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T00:00:00Z","timestamp":1708473600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hubei Provincial Natural Science Foundation of China","award":["2022CFB841"],"award-info":[{"award-number":["2022CFB841"]}]},{"name":"Scientific Research Program of Wuhan Municipal Health Commission","award":["WX20D15"],"award-info":[{"award-number":["WX20D15"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Objective<\/jats:title>\n<jats:p>To generate a mouse model carrying <jats:italic>TTN<\/jats:italic>tv Y4370* simulating the newly discovered human heterozygous nonsense <jats:italic>TTN<\/jats:italic>tv c.13254T&gt;G (p.Tyr4418Ter) to supplement and improve the functional evidence of pathogenic mutation <jats:italic>TTN<\/jats:italic>tv c.13254T&gt;G on the pathogenic type of dilated cardiomyopathy.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>We generated 4 mice carrying <jats:italic>TTN<\/jats:italic>tv 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 <jats:italic>TTN<\/jats:italic><jats:sup><jats:italic>+\/-<\/jats:italic><\/jats:sup> mice and 4 wild-type (WT) mice.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>For the two-month-old <jats:italic>TTN<\/jats:italic><jats:sup><jats:italic>+\/-<\/jats:italic><\/jats:sup> 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 <jats:italic>TTN<\/jats:italic><jats:sup><jats:italic>+\/-<\/jats:italic><\/jats:sup> mice were obviously increased compared with WT mice.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p><jats:italic>TTN<\/jats:italic>tv Y4370* could lead to cardiac structure and function alterations in mice, supplementing the evidence of <jats:italic>TTN<\/jats:italic>tv c.13254T&gt;G pathogenicity in human.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0296802","type":"journal-article","created":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T18:26:08Z","timestamp":1708539968000},"page":"e0296802","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["The TTN p. 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