title: Loss of plakoglobin immunoreactivity in intercalated discs in arrhythmogenic right ventricular cardiomyopathy: protein mislocalization versus epitope masking.
abstract: OBJECTIVE
  To examine the relevance and cause of reduced plakoglobin IF in intercalated discs for arrhythmogenic right ventricular cardiomyopathy (ARVC) and ARVC-like disease in mouse and human.
  
  
  RESULTS
  Normalized semi-quantitative IF measurements were performed in a standardized format in desmoglein 2-mutant mice with an ARVC-like phenotype (n = 6) and in cardiac biopsies from humans with ARVC and non-ARVC heart disease (n = 10). Reduced plakoglobin staining was detectable in ARVC only with one antibody directed against a defined epitope but not with three other antibodies reacting with different epitopes of plakoglobin.
  
  
  CONCLUSIONS
  Reduced plakoglobin staining in intercalated discs of heart tissue from human ARVC patients and in a murine ARVC model is caused by alterations in epitope accessibility and not by protein relocalization.
authors.affiliation: Institute of Molecular and Cellular Anatomy, RWTH Aachen University, Wendlingweg 2, Aachen 52074, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Kant
authors.affiliation: Institute of Molecular and Cellular Anatomy, RWTH Aachen University, Wendlingweg 2, Aachen 52074, Germany.
authors.forename: Claudia A
authors.initials: CA
authors.lastname: Krusche
authors.affiliation: Herz- und Diabeteszentrum NRW, Klinik für Thorax- und Kardiovaskularchirurgie, Erich und Hanna Klessmann-Institut für Kardiovaskuläre Forschung und Entwicklung, Bad Oeynhausen, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Gaertner
authors.affiliation: Herz- und Diabeteszentrum NRW, Klinik für Thorax- und Kardiovaskularchirurgie, Erich und Hanna Klessmann-Institut für Kardiovaskuläre Forschung und Entwicklung, Bad Oeynhausen, Germany.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Milting
authors.affiliation: Institute of Molecular and Cellular Anatomy, RWTH Aachen University, Wendlingweg 2, Aachen 52074, Germany rleube@ukaachen.de.
authors.forename: Rudolf E
authors.initials: RE
authors.lastname: Leube
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D019571:Arrhythmogenic Right Ventricular Dysplasia / Q000235:genetics / Q000378:metabolism*; D051180:Desmoplakins / Q000235:genetics / Q000378:metabolism*; D003896:Desmosomes / Q000378:metabolism; D004195:Disease Models, Animal; D000939:Epitopes / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D018345:Mice, Knockout; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D010641:Phenotype; D055815:Young Adult; D051185:gamma Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D051180:Desmoplakins; D000939:Epitopes; C495292:JUP protein, human; C495293:Jup protein, mouse; D051185:gamma Catenin
keywords: Area composita; Armadillo repeat; Desmosome; Wnt signalling; β-catenin