In Boxers with ARVC, β-catenin and striatin colocalized with the endoplasmic reticulum, and β-catenin amounts increased by 50%, suggesting inhibited trafficking of Wnt pathway proteins.
Case-Control (n=20)
Effect estimate: 50% increase in β-catenin
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.
Oxford et al. (Fri,) conducted a case-control in Arrhythmogenic right ventricular cardiomyopathy (ARVC) (n=20). Arrhythmogenic right ventricular cardiomyopathy (ARVC) vs. Dogs without ARVC was evaluated on Localization and amount of β-catenin and striatin in right ventricular samples (50% increase in β-catenin). In Boxers with ARVC, β-catenin and striatin colocalized with the endoplasmic reticulum, and β-catenin amounts increased by 50%, suggesting inhibited trafficking of Wnt pathway proteins.