References
Query Results -- Details
MGI Accession ID: MGI:3583403
J Number: J:99655
Other Accession IDs:
Title: Endoplasmic reticulum stress modulates the response of myelinating oligodendrocytes to the immune cytokine interferon-gamma.
Authors: Lin W; Harding HP; Ron D; Popko B
Journal: J Cell Biol
Volume: 169
Issue: 4
Date: 2005 May 23
Year: 2005
Pages: 603-12
Review Status: Peer Reviewed
Abstract:
Interferon-gamma (IFN-gamma) is believed to contribute to immune-mediated demyelinating disorders by targeting the myelin-producing oligodendrocyte, a cell known to be highly sensitive to the disruption of protein synthesis and to the perturbation of the secretory pathway. We found that apoptosis induced by IFN-gamma in cultured rat oligodendrocytes was associated with endoplasmic reticulum (ER) stress. ER stress also accompanied oligodendrocyte apoptosis and hypomyelination in transgenic mice that inappropriately expressed IFN-gamma in the central nervous system (CNS). Compared with a wild-type genetic background, the enforced expression of IFN-gamma in mice that were heterozygous for a loss of function mutation in pancreatic ER kinase (PERK) dramatically reduced animal survival, promoted CNS hypomyelination, and enhanced oligodendrocyte loss. PERK encodes an ER stress-inducible kinase that phosphorylates eukaryotic translation initiation factor 2alpha and specifically maintains client protein homeostasis in the stressed ER. Therefore, the hypersensitivity of PERK+/- mice to IFN-gamma implicates ER stress in demyelinating disorders that are induced by CNS inflammation.
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