Abstract
BackgroundInherited dilated cardiomyopathy (DCM) is a progressive disease that often results in death from congestive heart failure (CHF) or sudden cardiac death (SCD). Mouse models with human DCM mutation are useful to investigate the developmental mechanisms of CHF and SCD, but knowledge of the severity of CHF in live mice is necessary. We aimed to diagnose CHF in live DCM model mice by measuring voluntary exercise using a running wheel and to determine causes of death in these mice.Methodology/Principal FindingsA knock-in mouse with a mutation in cardiac troponin T (ΔK210) (DCM mouse), which results in frequent death with a t1/2 of 70 to 90 days, was used as a DCM model. Until 2 months of age, average wheel-running activity was similar between wild-type and DCM mice (approximately 7 km/day). At approximately 3 months, some DCM mice demonstrated low running activity (LO: <1 km/day) while others maintained high running activity (HI: >5 km/day). In the LO group, the lung weight/body weight ratio was much higher than that in the other groups, and the lungs were infiltrated with hemosiderin-loaded alveolar macrophages. Furthermore, echocardiography showed more severe ventricular dilation and a lower ejection fraction, whereas Electrocardiography (ECG) revealed QRS widening. There were two patterns in the time courses of running activity before death in DCM mice: deaths with maintained activity and deaths with decreased activity.Conclusions/SignificanceOur results indicate that DCM mice with low running activity developed severe CHF and that running wheels are useful for detection of CHF in mouse models. We found that approximately half of ΔK210 DCM mice die suddenly before onset of CHF, whereas others develop CHF, deteriorate within 10 to 20 days, and die.
Highlights
Inherited dilated cardiomyopathy (DCM) is a progressive disease characterized by left ventricular dilatation and systolic dysfunction, and it is often associated with severe heart failure (HF) and sudden cardiac death (SCD) [1,2,3]
Conclusions/Significance: Our results indicate that DCM mice with low running activity developed severe congestive heart failure (CHF) and that running wheels are useful for detection of CHF in mouse models
By measuring the time course of running activities in individual mice, we demonstrated that causes of death in deletion mutation of K210 (DK210) DCM mice include 1) SCD without signs of CHF (
Summary
Inherited dilated cardiomyopathy (DCM) is a progressive disease characterized by left ventricular dilatation and systolic dysfunction, and it is often associated with severe heart failure (HF) and sudden cardiac death (SCD) [1,2,3]. Lethal arrhythmia is strongly suspected as a cause of sudden death: clear evidence for arrhythmia has not been documented in many cases. These reports raise important questions about how and when these symptoms appear in inherited DCM carriers. Inherited dilated cardiomyopathy (DCM) is a progressive disease that often results in death from congestive heart failure (CHF) or sudden cardiac death (SCD). We aimed to diagnose CHF in live DCM model mice by measuring voluntary exercise using a running wheel and to determine causes of death in these mice
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
