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Progressive Atrioventricular Conduction Block in a Mouse Myotonic Dystrophy Model

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Journal of Interventional Cardiac Electrophysiology Aims and scope Submit manuscript

Abstract

Introduction: Myotonic dystrophy is caused by expansion of a CTG trinucleotide repeat on human chromosome 19, and leads to progressive skeletal myopathy and atrioventricular conduction disturbances. A murine model of myotonic dystrophy has been designed by targeted disruption of the myotonic dystrophy protein kinase (DMPK) gene. The DMPK-deficient mice display abnormalities in A-V conduction characteristics, similar to the human cardiac phenotype. The purpose of this study was to determine whether age-related progression of A-V block occurs in a mouse model of DMPK-deficiency.

Methods and Results: Surface ECGs and intracardiac electrophysiology (EP) studies were performed in 60 immature and 90 adult homozygous (DMPK), heterozygous (DMPK), and wild-type (WT) DMPK control mice. Complete studies were obtained on 141 of 150 mice. The RR, PR, QRS, and QT intervals were measured on ECG. Sinus node recovery time, AV refractory periods, paced AV Wenckebach and 2:1 block cycle lengths, atrial and ventricular effective refractory periods were compared between genotypes and age groups. There were no differences in ECG intervals or EP findings in the young mutant mice, but progressive PR prolongation in older mice. The A-V conduction defects are also sensitive to DMPK gene dosage. Adult DMPK mice develop 1°, 2° and 3° A-V block, whereas DMPK mice develop only 1° heart block.

Conclusion: These data demonstrate that both age and DMPK dose are important factors regulating cardiac conduction in myotonic dystrophy. This mouse model of DM is remarkably similar to the human phenotype, with age-related progression in atrioventricular conduction defects.

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Authors and Affiliations

  1. Department of Cardiology, Boston Children's Hospital, Harvard Medical School, Boston, MA

    Charles I. Berul, Colin T. Maguire & Josef Gehrmann

  2. Institute for Genetic Medicine, University of Southern California, Los Angeles, CA

    Sita Reddy

Authors
  1. Charles I. Berul
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  2. Colin T. Maguire
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  3. Josef Gehrmann
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  4. Sita Reddy
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Berul, C.I., Maguire, C.T., Gehrmann, J. et al. Progressive Atrioventricular Conduction Block in a Mouse Myotonic Dystrophy Model. J Interv Card Electrophysiol 4, 351–358 (2000). https://doi.org/10.1023/A:1009842114968

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