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

Mark A. Oyama, Steve Reiken, Stephan E. Lehnart, Sridar V. Chittur, Kathryn M. Meurs, Joshua A Stern, Andrew R. Marks

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

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 Ca2+ 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 Ca2+ leak-induced ventricular arrhythmias and heart disease in Boxer dogs with ARVC.

Original languageEnglish (US)
Pages (from-to)1-10
Number of pages10
JournalJournal of Veterinary Cardiology
Volume10
Issue number1
DOIs
StatePublished - Jun 2008
Externally publishedYes

Keywords

  • Calcium
  • Dilated cardiomyopathy
  • Ryanodine receptor

ASJC Scopus subject areas

  • veterinary(all)
  • Physiology

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