Linked Life Data

10650874

Source:http://linkedlifedata.com/resource/pubmed/id/10650874

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2000-2-17
pubmed:abstractText
The immune cytokine interferon-gamma (IFN-gamma) is believed to be a key agent in the pathogenesis of immune-mediated demyelinating disorders. We have examined the possibility that one effect of this cytokine involves overloading the endoplasmic reticulum (ER) of oligodendrocytes through the induction of major histocompatibility complex (MHC) class I heavy chain (HC) gene expression. For these studies, we have utilized several genetic mouse models that yield different subcellular localizations of HC in oligodendrocytes. We show that transgenic mice that ectopically express HC in oligodendrocytes (MBP/MHC class I mice) fail to transport HC past the ER. These mice are hypomyelinated and have a tremoring phenotype. When oligodendrocytes deficient in beta-2 microglobulin (beta2m), which is required for MHC class I assembly and transport, were treated with IFN-gamma in vitro, HC was transported past the ER to the trans-Golgi network but not onto the cell surface. When an asymptomatic line of mice that expresses MHC class I in the CNS due to transgene-derived IFN-gamma (MBP/IFN-gamma mice) was crossed onto the beta2m-/- background, the resulting mice were asymptomatic. In contrast, increasing the amount of MHC class I protein transported through the ER in MBP/MHC class I transgenic mice, by crossing them to the asymptomatic MBP/IFN-gamma mice, exacerbated their phenotype. Taken together, these data indicate that the ER is a sensitive site in oligodendrocytes for accumulation of MHC class I HC and suggest a molecular mechanism for IFN-gamma's deleterious effects on these cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0360-4012
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
59
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
160-9
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Major histocompatibility complex heavy chain accumulation in the endoplasmic reticulum of oligodendrocytes results in myelin abnormalities.
pubmed:affiliation
Neuroscience Center, University of North Carolina at Chapel Hill, 27599-7250, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.