title: Desmin-related cardiomyopathy in transgenic mice: a cardiac amyloidosis.
abstract: An R120G missense mutation in the small heat shock protein alpha-B-crystallin (CryAB(R120G)) 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 CryAB(R120G) 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 CryAB(R120G) establish the necessity and sufficiency of CryAB(R120G) 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.
authors.affiliation: Division of Molecular Cardiovascular Biology, Cincinnati Children's Hospital Medical Center, Children's Hospital Research Foundation, Mail Location Code 7020, 3333 Burnet Avenue, OH 45229-3039, USA.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sanbe
authors.forename: Hanna
authors.initials: H
authors.lastname: Osinska
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Saffitz
authors.forename: Charles G
authors.initials: CG
authors.lastname: Glabe
authors.forename: Rakez
authors.initials: R
authors.lastname: Kayed
authors.forename: Alina
authors.initials: A
authors.lastname: Maloyan
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Robbins
mesh_terms: D000686:Amyloidosis / Q000209:etiology* / Q000378:metabolism; D000818:Animals; D009202:Cardiomyopathies / Q000209:etiology* / Q000378:metabolism; D002478:Cells, Cultured; D003893:Desmin / Q000032:analysis / Q000502:physiology*; D006333:Heart Failure / Q000378:metabolism; D006801:Humans; D002479:Inclusion Bodies / Q000737:chemistry*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D038203:alpha-Crystallin B Chain / Q000032:analysis / Q000502:physiology*
chemical_list: D003893:Desmin; D038203:alpha-Crystallin B Chain