Troponin T amino acid mutation (ΔK210) knock-in mice as a neonatal dilated cardiomyopathy model
Troponin T amino acid mutation (ΔK210) knock-in mice as a neonatal dilated cardiomyopathy model
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DOI：
10.1038/s41390-020-1016-1
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发表时间：
2020-06
影响因子：
3.6
通讯作者：
J. Tanihata;Teruyuki Fujii;Shunsuke Baba;Yoshitaka Fujimoto;S. Morimoto;S. Minamisawa
中科院分区：
文献类型：
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作者：
J. Tanihata;Teruyuki Fujii;Shunsuke Baba;Yoshitaka Fujimoto;S. Morimoto;S. Minamisawa
背景儿童扩张型心肌病 (DCM) 通常与较低的发病率和死亡率相关，并且表现出与成人 DCM 不同的病理实体。由于患者数量有限且缺乏良好的动物模型，小儿 DCM 的分子机制仍知之甚少。本研究的目的是建立新生儿DCM动物模型并鉴定早期进展因素。方法分析纯合子ΔK210敲入（TNNT2ΔK210/ΔK210）小鼠的心脏表型和综合基因表达谱，并与0日龄和1周龄时的TNNT2+/ΔK210和野生型小鼠进行比较。与TNNT2+/ΔK210和野生型小鼠相比，在TNNT2ΔK210/ΔK210小鼠中已经增加。 0 日龄和 1 周龄 TNNT2ΔK210/ΔK210 小鼠的超声心动图检查显示儿童 DCM 的相似表型。此外，TNNT2ΔK210/ΔK210小鼠心室组织中的多个基因显着上调，KEGG PATHWAY分析揭示了癌症和粘着斑等可能与DCM发病和发展相关的几个重要通路。结论TNNT2ΔK210/ΔK210小鼠在出生时就已经发生了DCM，这表明它们应该是鉴定DCM早期进展因素的优秀动物模型。 DCM.ImpactTNNT2ΔK210/ΔK210小鼠是DCM优良的动物模型。TNNT2ΔK210/ΔK210小鼠是鉴定DCM早期进展因素的优良动物模型。KEGG PATHWAY分析显示癌症、粘着斑等多个重要通路可能与新生儿DCM的发病和发展有关。
BackgroundDilated cardiomyopathy (DCM) in children is often associated with poor morbidity and mortality and exhibits distinct pathological entities from those of adult DCM. Owing to the limited number of patients and the lack of a good animal model, the molecular mechanisms underlying pediatric DCM remain poorly understood. The purpose of this study is to establish an animal model of neonatal DCM and identify early progression factors.MethodsCardiac phenotypes and comprehensive gene expression profiles in homozygous ΔK210 knock-in (TNNT2ΔK210/ΔK210) mice were analyzed and compared toTNNT2+/ΔK210and wild-type mice at 0 days and 1 week of age.ResultsImmediately after birth, the cardiac weight inTNNT2ΔK210/ΔK210mice was already increased compared to that inTNNT2+/ΔK210and wild-type mice. Echocardiographic examination of 0-day-old and 1-week-oldTNNT2ΔK210/ΔK210mice revealed similar phenotypes of pediatric DCM. In addition, several genes were significantly upregulated in the ventricular tissues ofTNNT2ΔK210/ΔK210mice, and the KEGG PATHWAY analysis revealed several important pathways such as cancer and focal adhesion that might be associated with the pathogenesis and development of DCM.ConclusionsTNNT2ΔK210/ΔK210mice have already developed DCM at birth, indicating that they should be an excellent animal model to identify early progression factors of DCM.ImpactTNNT2ΔK210/ΔK210mice are excellent animal model for DCM.TNNT2ΔK210/ΔK210mice are excellent animal model to identify early progression factors of DCM.KEGG PATHWAY analysis revealed that several important pathways such as cancer and focal adhesion might be associated with the pathogenesis and development of neonatal DCM.