Aim. Desmin filaments, the muscle-specific intermediate filaments are a major component of the cytoskeleton in muscle tissue including skeletal, cardiac, and smooth muscle. Deemin filament, formed mainly by polymerization of desmin protein molecules insert into the desmosomes at the intercalated discs via its interaction with desmoplakin(DP). Mutations in the desmin gene were linked to desmin-related myopathy(DRM) and dilated cardiomyopathy. This study was to test the hypothesis that disruption of the desmin filament network alters the expression and/or distribution of desmosomal proteins. Methods. A transgenic mouse model expressing a 7-amino acid(R173-E179) deletion desmin specifically in the - heart(D7-des) was used. Total lysates and Triton extracts of ventricular myocardium from one month old mice were immunoblotted for DP and plakoglobin(PG). Frozen ventricular myocardial sections were immunolabeled with the same antibodies plus desmin and desmosomes were visualized by confocal microscopy. Results. In the D7-des mouse hearts, immunofluorescence labeling confirmed reported abnormal desmin distribution including disruption of the desmin network and presence of aberrant desmin aggregates, while in the non-transgenic (NTG) hearts desmin labeling showed clear transverse striations. A prominent increase of DP in D7-des was observed in either total lyastes or TritonX-100 insoluble fractions(TIF). Consistently, immunofluorescence confocal microscopy showed DP fluorescence density was increased significantly and DP distribution altered. There were no changes in DP between wild-type transgenic mice (WT-des) and NTG. No differences in expression of PG were observed among the three groups. Conclusion. Expression of a human DRC-linked mutant desmin protein in mice remodels the desmosomes through altering the expression and distribution of DP. This may impair the mechanical coupling among cardiac myocytes and contribute to arrhythmias remodeling and contractile dysfunction in desmin-related cardiomyopathy.
|Original language||English (US)|
|Number of pages||3|
|Journal||Chinese Journal of Clinical Rehabilitation|
|State||Published - Jul 2003|
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