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  • Arrhythmogenic right ventricular cardiomyopathy in Boxer dogs is associated with calstabin2 deficiency.

    J Vet Cardiol. 10(1):1-10. doi: 10.1016/j.jvc.2008.04.003. June 2008. View on PubMed.
  • Authors

    Oyama MA, Reiken S, Lehnart SE, Chittur SV, Meurs KM, Stern J, and Marks AR
  • Abstract

    OBJECTIVETo examine the presence and effect of calstabin2-deficiency in Boxer dogs with arrhythmogenic right ventricular cardiomyopathy (ARVC).ANIMALSThirteen Boxer dogs with ARVC.MATERIALS AND METHODSTissue samples were collected for histopathology, oligonucleotide microarray, PCR, immunoelectrophoresis, ryanodine channel immunoprecipitation and single-channel recordings, and calstabin2 DNA sequencing.RESULTSIn 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.CONCLUSIONSCalstabin2 deficiency is a potential mechanism of Ca(2+) leak-induced ventricular arrhythmias and heart disease in Boxer dogs with ARVC.

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