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Published on: December 22, 2023
Arrhythmogenic right ventricular cardiomyopathy in Boxer dogs is associated with calstabin2 deficiency
Mark A Oyama1, Steve Reiken, Stephan E Lehnart
1University of Pennsylvania, Philadelphia, PA, USA, USA. maoyama@vet.upenn.edu
Objective:
To examine the presence and effect of calstabin2-deficiency in Boxer dogs with arrhythmogenic right ventricular cardiomyopathy (ARVC).
Animals:
Thirteen Boxer dogs with ARVC.
Materials And Methods:
Tissue samples were collected for histopathology, oligonucleotide microarray, PCR, immunoelectrophoresis, ryanodine channel immunoprecipitation and single-channel recordings, and calstabin2 DNA sequencing.
Results:
In cardiomyopathic Boxer dogs, myocardial calstabin2 mRNA and protein were significantly decreased as compared to healthy control dogs (calstabin2 protein normalized to tetrameric cardiac ryanodine receptor (RyR2) complex: affected, 0.51+/-0.04; control, 3.81+/-0.22; P<0.0001). Calstabin2 deficiency in diseased dog hearts was associated with a significantly increased open probability of single RyR2 channels indicating intracellular Ca(2+) leak. PCR-based sequencing of the promoter, exonic and splice site regions of the canine calstabin2 gene did not identify any causative mutations.
Conclusions:
Calstabin2 deficiency is a potential mechanism of Ca(2+) leak-induced ventricular arrhythmias and heart disease in Boxer dogs with ARVC.
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