Cardiac Electrophysiologic Abnormalities in the CREBA133 Transgenic Mouse Model of Idiopathic Dilated Cardiomyopathy


  • This work was supported by NHLBI Grant RO1-HL61479.

  • The first two authors and the last two authors contributed equally to this work.

  • Manuscript received 11 January 2002; Accepted for publication 3 June 2003.

Address for correspondence: Paul J. Wang, M.D., Cardiovascular Medicine, Stanford University Medical Center, 300 Pasteur Drive, H2146, MC5233, Stanford CA 94305-5288.


Introduction: 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 α-MHC promoter and displaying dilated cardiomyopathy would exhibit electrophysiologic abnormalities similar to those observed in human cardiomyopathy.

Methods and 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.

Conclusion: 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. (J Cardiovasc Electrophysiol, Vol. 14, pp. 982-989, September 2003)