Cardiac electrophysiologic abnormalities in the CREBA133 transgenic mouse model of idiopathic dilated cardiomyopathy.
BACKGROUND
We hypothesized that the transgenic mice expressing a dominant-negative form of the CREB transcription factor (CREBA133) under the control of the cardiac myocyte-specific alpha-MHC promoter and displaying dilated cardiomyopathy would exhibit electrophysiologic abnormalities similar to those observed in human cardiomyopathy.


RESULTS
Invasive electrophysiologic studies were performed on two age groups of mice: 11-week-old mice (n = 20, 9 transgenic mice and 11 wild-type controls) and 17-week-old mice (n = 16, 7 transgenic mice and 9 wild-type controls). Five additional transgenic mice underwent ambulatory ECG monitoring to determine the cause of death. The 11-week-old CREBA133 transgenic mice had longer PR and AH intervals than 11-week-old wild-type controls (P < 0.001), whereas at 17 weeks of age the transgenic mice also demonstrated increased HV intervals and widened QRS duration (P < 0.05). At both 11 weeks and 17 weeks of age, AV Wenckebach cycle length, 2:1 AV cycle length, and AV nodal functional and effective refractory periods were significantly longer in transgenic mice than in controls (P < 0.05). Although no ventricular arrhythmias were inducible at 11 weeks of age, at 17 weeks of age, ventricular tachycardia was induced in 4 of the 7 CREBA133 transgenic mice but in none of the 9 wild-type controls. All 5 CREBA133 transgenic mice that underwent ambulatory ECG monitoring revealed high-grade AV block, but not ventricular arrhythmia, at the time of death.


CONCLUSIONS
These data suggest that CREBA133 transgenic mice manifest abnormalities of AV nodal and infra-Hisian conduction and inducibility of ventricular arrhythmia, which are characteristics of human dilated cardiomyopathy.
Zhu
Wei
W
Cardiac Arrhythmia Service, New England Medical Center, Boston, MA, USA.
Saba
Samir
S
D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000235:genetics / Q000503:physiopathology*; D017362:Cyclic AMP Response Element-Binding Protein; D004195:Disease Models, Animal; D004562:Electrocardiography; D015716:Electrocardiography, Ambulatory; D022062:Electrophysiologic Techniques, Cardiac; D005799:Genes, Dominant; D006321:Heart / Q000503:physiopathology*; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
C482604:CREBA133 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D014157:Transcription Factors