Change in β-catenin localization suggests involvement of the canonical Wnt pathway in Boxer dogs with arrhythmogenic right ventricular cardiomyopathy

J Vet Intern Med. Jan-Feb 2014;28(1):92-101. doi: 10.1111/jvim.12238. Epub 2013 Nov 8.

Abstract

Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited myocardial disease with high prevalence in the Boxer dog population. It is characterized by replacement of the myocardium with fatty or fibro-fatty tissue. Several mechanisms for the development of ARVC have been suggested, including dysfunction of the canonical Wnt pathway, which is linked to many cellular functions, including growth and differentiation of adipocytes.

Hypothesis: Wnt pathway dysfunction is involved in the development of ARVC in the Boxer as evidenced by mislocalization of β-catenin, an integral Wnt pathway modulator, and striatin, a known Wnt pathway component.

Animals: Five dogs without ARVC and 15 Boxers with ARVC were identified by 24-hour Holter monitoring and histopathologic examination of the heart.

Methods: Right ventricular samples were collected and examined using confocal microscopy, Western blots, and quantitative (q) PCR.

Results: Confocal microscopy indicated that β-catenin localized at sites of cell-to-cell apposition, and striatin localized in a diffuse intracellular pattern in hearts without ARVC. In hearts affected with ARVC, both β-catenin and striatin were colocalized with the endoplasmic reticulum (ER) marker calreticulin. Western blots indentified a 50% increase in the amount of β-catenin in ARVC samples. No change in β catenin mRNA was detected using qPCR.

Conclusions: Our data suggest that trafficking of Wnt pathway proteins from the ER to their proper location within the cell is inhibited in Boxers with ARVC. These results suggest that disturbances in the Wnt pathway may play a role in the development of ARVC in the Boxer.

Keywords: ARVC; Canine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arrhythmogenic Right Ventricular Dysplasia / genetics
  • Arrhythmogenic Right Ventricular Dysplasia / pathology
  • Arrhythmogenic Right Ventricular Dysplasia / veterinary*
  • Blotting, Western / veterinary
  • Dog Diseases / genetics
  • Dog Diseases / pathology*
  • Dogs
  • Female
  • Histocytochemistry / veterinary
  • Male
  • Microscopy, Confocal / veterinary
  • RNA / chemistry
  • RNA / genetics
  • Real-Time Polymerase Chain Reaction / veterinary
  • Statistics, Nonparametric
  • Wnt Signaling Pathway / genetics
  • Wnt Signaling Pathway / physiology*
  • beta Catenin / genetics
  • beta Catenin / physiology*

Substances

  • beta Catenin
  • RNA