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

34 Citations (Scopus)

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

Fingerprint

Arrhythmogenic Right Ventricular Dysplasia
Boxer (dog breed)
cardiomyopathy
Dogs
Ryanodine Receptor Calcium Release Channel
dogs
Deficiency Diseases
Ryanodine
Polymerase Chain Reaction
Immunoelectrophoresis
ryanodine receptors
calcium
immunoelectrophoresis
Oligonucleotide Array Sequence Analysis
DNA Sequence Analysis
Immunoprecipitation
arrhythmia
heart diseases
oligonucleotides
Canidae

Keywords

  • Calcium
  • Dilated cardiomyopathy
  • Ryanodine receptor

ASJC Scopus subject areas

  • veterinary(all)
  • Physiology

Cite this

Arrhythmogenic right ventricular cardiomyopathy in Boxer dogs is associated with calstabin2 deficiency. / Oyama, Mark A.; Reiken, Steve; Lehnart, Stephan E.; Chittur, Sridar V.; Meurs, Kathryn M.; Stern, Joshua A; Marks, Andrew R.

In: Journal of Veterinary Cardiology, Vol. 10, No. 1, 06.2008, p. 1-10.

Research output: Contribution to journalArticle

Oyama, Mark A. ; Reiken, Steve ; Lehnart, Stephan E. ; Chittur, Sridar V. ; Meurs, Kathryn M. ; Stern, Joshua A ; Marks, Andrew R. / Arrhythmogenic right ventricular cardiomyopathy in Boxer dogs is associated with calstabin2 deficiency. In: Journal of Veterinary Cardiology. 2008 ; Vol. 10, No. 1. pp. 1-10.
@article{dd9eb79cfd9c4f888d92f124891ebc59,
title = "Arrhythmogenic right ventricular cardiomyopathy in Boxer dogs is associated with calstabin2 deficiency",
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.",
keywords = "Calcium, Dilated cardiomyopathy, Ryanodine receptor",
author = "Oyama, {Mark A.} and Steve Reiken and Lehnart, {Stephan E.} and Chittur, {Sridar V.} and Meurs, {Kathryn M.} and Stern, {Joshua A} and Marks, {Andrew R.}",
year = "2008",
month = "6",
doi = "10.1016/j.jvc.2008.04.003",
language = "English (US)",
volume = "10",
pages = "1--10",
journal = "Journal of Veterinary Cardiology",
issn = "1760-2734",
publisher = "Elsevier",
number = "1",

}

TY - JOUR

T1 - Arrhythmogenic right ventricular cardiomyopathy in Boxer dogs is associated with calstabin2 deficiency

AU - Oyama, Mark A.

AU - Reiken, Steve

AU - Lehnart, Stephan E.

AU - Chittur, Sridar V.

AU - Meurs, Kathryn M.

AU - Stern, Joshua A

AU - Marks, Andrew R.

PY - 2008/6

Y1 - 2008/6

N2 - 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.

AB - 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.

KW - Calcium

KW - Dilated cardiomyopathy

KW - Ryanodine receptor

UR - http://www.scopus.com/inward/record.url?scp=45049086883&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=45049086883&partnerID=8YFLogxK

U2 - 10.1016/j.jvc.2008.04.003

DO - 10.1016/j.jvc.2008.04.003

M3 - Article

C2 - 18515204

AN - SCOPUS:45049086883

VL - 10

SP - 1

EP - 10

JO - Journal of Veterinary Cardiology

JF - Journal of Veterinary Cardiology

SN - 1760-2734

IS - 1

ER -