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标题：Desmin-related cardiomyopathy in transgenic mice: A cardiac amyloidosis
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作者：Atsushi Sanbe ; Hanna Osinska ; Jeffrey E. Saffitz 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2004
卷号：101
期号：27
页码：10132-10136
DOI：10.1073/pnas.0401900101
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：An R120G missense mutation in the small heat shock protein {alpha}-B-crystallin (CryABR120G) causes desmin-related cardiomyopathy (DRM). DRM is characterized by the formation of aggregates containing CryAB and desmin, and it can be recapitulated in transgenic mice by cardiac-specific expression of the mutant protein. In this article, we show that expression of CryABR120G leads to the formation of electron-dense bodies characteristic of the DRMs and identify these bodies as aggresomes, which are characteristic of the neurodegenerative diseases. Cardiomyocytes transfected with adenovirus containing CryABR120G establish the necessity and sufficiency of CryABR120G expression for aggresome formation. The commonality of these aggresomes with oligomeric protein aggregates found in the amyloid-related degenerative diseases was corroborated by the presence of high levels of amyloid oligomers that may represent a primary toxic species in the amyloid diseases. These oligomeric amyloid intermediates are present also in cardiomyocytes derived from many human dilated and hypertrophic cardiomyopathies.