Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1996-12-6
pubmed:abstractText
Circumstantial and experimental evidence has implicated the immune cytokine interferon-gamma (IFN-gamma) as a key mediator in the pathological changes that are observed in many demyelinating disorders, including the most common human demyelinating disease, multiple sclerosis. To produce an animal model with which to study the effects of IFN-gamma on the CNS, we have generated transgenic mice in which the expression of IFN-gamma has been placed under the transcriptional control of the myelin basic protein (MBP) gene. Transgenic mice generated with this construct have a shaking/shivering phenotype that is similar to that observed in naturally occurring mouse models of hypomyelination (e.g., shiverer, jimpy, quaking), and these transgenic animals have dramatically less CNS myelin than control animals. Reactive gliosis and increased macrophage/microglial F4/80 immunostaining were also observed. Additionally, major histocompatibility complex (MHC) class I and class II mRNA levels were increased in the CNS of MBP/IFN-gamma transgenic mice, and the increase in MHC class I mRNA expression was detected in both white and gray matter regions. Furthermore, cerebellar granule cell migration was abnormal in these animals. These results strongly support the hypothesis that IFN-gamma is a key effector molecule in immune-mediated demyelinating disorders and indicate that the presence of this cytokine in the CNS may also disrupt the developing nervous system.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1044-7431
pubmed:author
pubmed:issnType
Print
pubmed:volume
7
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
354-70
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:8812062-Animals, pubmed-meshheading:8812062-Blotting, Northern, pubmed-meshheading:8812062-Central Nervous System, pubmed-meshheading:8812062-Cerebellum, pubmed-meshheading:8812062-Demyelinating Diseases, pubmed-meshheading:8812062-Gene Expression, pubmed-meshheading:8812062-Gliosis, pubmed-meshheading:8812062-Histocompatibility Antigens Class I, pubmed-meshheading:8812062-Histocompatibility Antigens Class II, pubmed-meshheading:8812062-Immunohistochemistry, pubmed-meshheading:8812062-In Situ Hybridization, pubmed-meshheading:8812062-Interferon-gamma, pubmed-meshheading:8812062-Macrophages, pubmed-meshheading:8812062-Mice, pubmed-meshheading:8812062-Mice, Transgenic, pubmed-meshheading:8812062-Myelin Sheath, pubmed-meshheading:8812062-RNA, Messenger, pubmed-meshheading:8812062-Transgenes
pubmed:year
1996
pubmed:articleTitle
Targeted CNS expression of interferon-gamma in transgenic mice leads to hypomyelination, reactive gliosis, and abnormal cerebellar development.
pubmed:affiliation
Department of Oral and Maxillofacial Surgery, University of North Carolina Neuroscience Center, Chapel Hill 27599-7250, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't