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http://purl.uniprot.org/citations/28339476http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/28339476http://www.w3.org/2000/01/rdf-schema#comment"

Background

Arrhythmogenic cardiomyopathy is an inherited heart muscle disorder leading to ventricular arrhythmias and heart failure, mainly as a result of mutations in cardiac desmosomal genes. Desmosomes are cell-cell junctions mediating adhesion of cardiomyocytes; however, the molecular and cellular mechanisms underlying the disease remain widely unknown. Desmocollin-2 is a desmosomal cadherin serving as an anchor molecule required to reconstitute homeostatic intercellular adhesion with desmoglein-2. Cardiac specific lack of desmoglein-2 leads to severe cardiomyopathy, whereas overexpression does not. In contrast, the corresponding data for desmocollin-2 are incomplete, in particular from the view of protein overexpression. Therefore, we developed a mouse model overexpressing desmocollin-2 to determine its potential contribution to cardiomyopathy and intercellular adhesion pathology.

Methods and results

We generated transgenic mice overexpressing DSC2 in cardiac myocytes. Transgenic mice developed a severe cardiac dysfunction over 5 to 13 weeks as indicated by 2D-echocardiography measurements. Corresponding histology and immunohistochemistry demonstrated fibrosis, necrosis and calcification which were mainly localized in patches near the epi- and endocardium of both ventricles. Expressions of endogenous desmosomal proteins were markedly reduced in fibrotic areas but appear to be unchanged in non-fibrotic areas. Furthermore, gene expression data indicate an early up-regulation of inflammatory and fibrotic remodeling pathways between 2 to 3.5 weeks of age.

Conclusion

Cardiac specific overexpression of desmocollin-2 induces necrosis, acute inflammation and patchy cardiac fibrotic remodeling leading to fulminant biventricular cardiomyopathy."xsd:string
http://purl.uniprot.org/citations/28339476http://purl.org/dc/terms/identifier"doi:10.1371/journal.pone.0174019"xsd:string
http://purl.uniprot.org/citations/28339476http://purl.uniprot.org/core/author"Rodriguez M."xsd:string
http://purl.uniprot.org/citations/28339476http://purl.uniprot.org/core/author"Martens K."xsd:string
http://purl.uniprot.org/citations/28339476http://purl.uniprot.org/core/author"Abdelfatah N."xsd:string
http://purl.uniprot.org/citations/28339476http://purl.uniprot.org/core/author"Brodehl A."xsd:string
http://purl.uniprot.org/citations/28339476http://purl.uniprot.org/core/author"Gerull B."xsd:string
http://purl.uniprot.org/citations/28339476http://purl.uniprot.org/core/author"Chen Y.X."xsd:string
http://purl.uniprot.org/citations/28339476http://purl.uniprot.org/core/author"Gordon P.M."xsd:string
http://purl.uniprot.org/citations/28339476http://purl.uniprot.org/core/author"Nygren A."xsd:string
http://purl.uniprot.org/citations/28339476http://purl.uniprot.org/core/author"Belke D.D."xsd:string
http://purl.uniprot.org/citations/28339476http://purl.uniprot.org/core/author"Diao C."xsd:string
http://purl.uniprot.org/citations/28339476http://purl.uniprot.org/core/author"Garnett L."xsd:string
http://purl.uniprot.org/citations/28339476http://purl.uniprot.org/core/date"2017"xsd:gYear
http://purl.uniprot.org/citations/28339476http://purl.uniprot.org/core/name"PLoS One"xsd:string
http://purl.uniprot.org/citations/28339476http://purl.uniprot.org/core/pages"e0174019"xsd:string
http://purl.uniprot.org/citations/28339476http://purl.uniprot.org/core/title"Transgenic mice overexpressing desmocollin-2 (DSC2) develop cardiomyopathy associated with myocardial inflammation and fibrotic remodeling."xsd:string
http://purl.uniprot.org/citations/28339476http://purl.uniprot.org/core/volume"12"xsd:string
http://purl.uniprot.org/citations/28339476http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/28339476
http://purl.uniprot.org/citations/28339476http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/28339476
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http://purl.uniprot.org/uniprot/#_A9X9L1-mappedCitation-28339476http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/28339476
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