Primary demyelination in transgenic mice expressing interferon-γ

Marc S. Horwitz, Claire F. Evans, Dorian B. McGavern, Moses Roriguez, Michael B.A. Oldstone

Research output: Contribution to journalArticlepeer-review

162 Scopus citations


Ever since the use of interferon-γ to treat patients with multiple sclerosis resulted in enhanced disease, the role of IFN-γ in demyelination has been under question. To address this issue directly, transgenic mice were generated that expressed the cDNA of murine IFN-γ 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-γ as an inducer of CNS demyelination leading to disease and provide new opportunities for dissecting the mechanism of demyelination.

Original languageEnglish (US)
Pages (from-to)1037-1041
Number of pages5
JournalNature Medicine
Issue number9
StatePublished - Sep 1997

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


Dive into the research topics of 'Primary demyelination in transgenic mice expressing interferon-γ'. Together they form a unique fingerprint.

Cite this