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G790del mutation in DSC2 alone is insufficient to develop the pathogenesis of ARVC in a mouse model

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart disease that causes heart failure and/or sudden cardiac death. Several desmosomal genes (DSC2, PKG, PKP2, DSP, and RyR2) are thought to be the causative gene involved in ARVC. Out of them, DSC2 mutations account...

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Detalles Bibliográficos
Autores principales: Hamada, Yoriomi, Yamamoto, Takeshi, Nakamura, Yoshihide, Sufu-Shimizu, Yoko, Nanno, Takuma, Fukuda, Masakazu, Ono, Makoto, Oda, Tesuro, Okuda, Shinichi, Ueyama, Takeshi, Kobayashi, Shigeki, Yano, Masafumi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6909225/
https://www.ncbi.nlm.nih.gov/pubmed/31872082
http://dx.doi.org/10.1016/j.bbrep.2019.100711
Descripción
Sumario:BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart disease that causes heart failure and/or sudden cardiac death. Several desmosomal genes (DSC2, PKG, PKP2, DSP, and RyR2) are thought to be the causative gene involved in ARVC. Out of them, DSC2 mutations account for 2% of ARVC genetic abnormalities. This study aimed to clarify the effect of G790del mutation in DSC2 on the arrhythmogenic mechanism and cardiac function in a mouse model. RESULT: Neither the heterozygous +/G790del nor homozygous G790del/G790del mice showed structural and functional defects in the right ventricle (RV) or lethal arrhythmia. The homozygous G790del/G790del 6-month-old mice slightly showed left ventricular (LV) dysfunction. Cell shortening decreased with prolongation of intracellular Ca2+ transient in cardiomyocytes isolated from the homozygous G790del/G790del mice, and spontaneous Ca(2+) transients were frequently observed in response to isoproterenol. CONCLUSIONS: G790del mutation in DSC2 was not relevant to the pathogenesis of ARVC, but showed a slight contractile dysfunction and Ca(2+) dysregulation in the LV.