title: Usefulness of running wheel for detection of congestive heart failure in dilated cardiomyopathy mouse model.
abstract: BACKGROUND
  Inherited 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.
  
  
  RESULTS
  A knock-in mouse with a mutation in cardiac troponin T (ΔK210) (DCM mouse), which results in frequent death with a t(1/2) 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
  Our 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.
authors: Department of Cellular and Molecular Pharmacology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors: Masami
authors: M
authors: Sugihara
authors: Fuminori
authors: F
authors: Odagiri
authors: Takeshi
authors: T
authors: Suzuki
authors: Takashi
authors: T
authors: Murayama
authors: Yuji
authors: Y
authors: Nakazato
authors: Kana
authors: K
authors: Unuma
authors: Ken-ichi
authors: K
authors: Yoshida
authors: Hiroyuki
authors: H
authors: Daida
authors: Takashi
authors: T
authors: Sakurai
authors: Sachio
authors: S
authors: Morimoto
authors: Nagomi
authors: N
authors: Kurebayashi
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers; D002423:Cause of Death; D004195:Disease Models, Animal; D004562:Electrocardiography; D005355:Fibrosis; D054144:Heart Failure, Diastolic / Q000175:diagnosis* / Q000209:etiology; D006801:Humans; D008168:Lung / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D020097:Natriuretic Peptide, Brain / Q000235:genetics / Q000378:metabolism; D009929:Organ Size; D010805:Physical Conditioning, Animal; D012420:Running
chemical_list: D015415:Biomarkers; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor
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