Troponin T amino acid mutation (ΔK210) knock-in mice as a neonatal dilated cardiomyopathy model

Background Dilated 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. Methods Cardiac phenotypes and comprehensive gene expression profiles in homozygous ΔK210 knock-in ( TNNT2 ΔK210/ΔK210 ) mice were analyzed and compared to TNNT2 +/ΔK210 and wild-type mice at 0 days and 1 week of age. Results Immediately after birth, the cardiac weight in TNNT2 ΔK210/ΔK210 mice was already increased compared to that in TNNT2 +/ΔK210 and wild-type mice. Echocardiographic examination of 0-day-old and 1-week-old TNNT2 ΔK210/ΔK210 mice revealed similar phenotypes of pediatric DCM. In addition, several genes were significantly upregulated in the ventricular tissues of TNNT2 ΔK210/ΔK210 mice, 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. Conclusions TNNT2 ΔK210/ΔK210 mice have already developed DCM at birth, indicating that they should be an excellent animal model to identify early progression factors of DCM. Impact TNNT2 ΔK210/ΔK210 mice are excellent animal model for DCM. TNNT2 ΔK210/ΔK210 mice 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.