Desmin-related cardiomyopathy in transgenic mice: A cardiac amyloidosis

Atsushi Sanbe, Hanna Osinska, Jeffrey E. Saffitz, Charles G. Glabe, Rakez Kayed, Alina Maloyan, Jeffrey Robbins

Research output: Contribution to journalArticle

204 Citations (Scopus)

Abstract

An R120G missense mutation in the small heat shock protein α-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.

Original languageEnglish (US)
Pages (from-to)10132-10136
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number27
DOIs
StatePublished - Jul 6 2004
Externally publishedYes

Fingerprint

Desmin
Amyloidosis
Cardiomyopathies
Amyloid
Transgenic Mice
Cardiac Myocytes
Small Heat-Shock Proteins
Crystallins
Poisons
Hypertrophic Cardiomyopathy
Dilated Cardiomyopathy
Missense Mutation
Mutant Proteins
Adenoviridae
Neurodegenerative Diseases
Electrons

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Desmin-related cardiomyopathy in transgenic mice : A cardiac amyloidosis. / Sanbe, Atsushi; Osinska, Hanna; Saffitz, Jeffrey E.; Glabe, Charles G.; Kayed, Rakez; Maloyan, Alina; Robbins, Jeffrey.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 101, No. 27, 06.07.2004, p. 10132-10136.

Research output: Contribution to journalArticle

Sanbe, Atsushi ; Osinska, Hanna ; Saffitz, Jeffrey E. ; Glabe, Charles G. ; Kayed, Rakez ; Maloyan, Alina ; Robbins, Jeffrey. / Desmin-related cardiomyopathy in transgenic mice : A cardiac amyloidosis. In: Proceedings of the National Academy of Sciences of the United States of America. 2004 ; Vol. 101, No. 27. pp. 10132-10136.
@article{e1339e99f4e84958b5706fae5e153ec6,
title = "Desmin-related cardiomyopathy in transgenic mice: A cardiac amyloidosis",
abstract = "An R120G missense mutation in the small heat shock protein α-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.",
author = "Atsushi Sanbe and Hanna Osinska and Saffitz, {Jeffrey E.} and Glabe, {Charles G.} and Rakez Kayed and Alina Maloyan and Jeffrey Robbins",
year = "2004",
month = "7",
day = "6",
doi = "10.1073/pnas.0401900101",
language = "English (US)",
volume = "101",
pages = "10132--10136",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "27",

}

TY - JOUR

T1 - Desmin-related cardiomyopathy in transgenic mice

T2 - A cardiac amyloidosis

AU - Sanbe, Atsushi

AU - Osinska, Hanna

AU - Saffitz, Jeffrey E.

AU - Glabe, Charles G.

AU - Kayed, Rakez

AU - Maloyan, Alina

AU - Robbins, Jeffrey

PY - 2004/7/6

Y1 - 2004/7/6

N2 - An R120G missense mutation in the small heat shock protein α-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.

AB - An R120G missense mutation in the small heat shock protein α-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.

UR - http://www.scopus.com/inward/record.url?scp=3042711961&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=3042711961&partnerID=8YFLogxK

U2 - 10.1073/pnas.0401900101

DO - 10.1073/pnas.0401900101

M3 - Article

C2 - 15220483

AN - SCOPUS:3042711961

VL - 101

SP - 10132

EP - 10136

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 27

ER -