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Publication : Primary demyelination in transgenic mice expressing interferon-gamma.

First Author  Horwitz MS Year  1997
Journal  Nat Med Volume  3
Issue  9 Pages  1037-1041
PubMed ID  9288735 Mgi Jnum  J:42790
Mgi Id  MGI:1096277 Doi  10.1038/nm0997-1037
Citation  Horwitz MS, et al. (1997) Primary demyelination in transgenic mice expressing interferon-gamma. Nat Med 3(9):1037-41
abstractText  Ever since the use of interferon-gamma to treat patients with multiple sclerosis resulted in enhanced disease, the role of IFN-gamma in demyelination has been under question. To address this issue directly, transgenic mice were generated that expressed the cDNA of murine IFN-gamma in the central nervous system by using an oligodendrocyte-specific promoter. Expression of the transgene occurred after 8 weeks of age, at which time the murine immune and central nervous systems are both fully developed. Directly associated with transgene expression, primary demyelination occurred and was accompanied by clinical abnormalities consistent with CNS disorders. Additionally, multiple hallmarks of immune-mediated CNS disease were observed including upregulation of MHC molecules, gliosis and lymphocytic infiltration. These results demonstrate a direct role for IFN-gamma as an inducer of CNS demyelination leading to disease and provide new opportunities for dissecting the mechanism of demyelination.
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