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 journalArticle

160 Citations (Scopus)

Abstract

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
Volume3
Issue number9
DOIs
StatePublished - Sep 1 1997

Fingerprint

Demyelinating Diseases
Interferons
Transgenic Mice
Neurology
Transgenes
Central Nervous System
Infiltration
Gliosis
Central Nervous System Diseases
Oligodendroglia
Complementary DNA
Multiple Sclerosis
Molecules
Up-Regulation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Horwitz, M. S., Evans, C. F., McGavern, D. B., Roriguez, M., & Oldstone, M. B. A. (1997). Primary demyelination in transgenic mice expressing interferon-γ. Nature Medicine, 3(9), 1037-1041. https://doi.org/10.1038/nm0997-1037

Primary demyelination in transgenic mice expressing interferon-γ. / Horwitz, Marc S.; Evans, Claire F.; McGavern, Dorian B.; Roriguez, Moses; Oldstone, Michael B.A.

In: Nature Medicine, Vol. 3, No. 9, 01.09.1997, p. 1037-1041.

Research output: Contribution to journalArticle

Horwitz, MS, Evans, CF, McGavern, DB, Roriguez, M & Oldstone, MBA 1997, 'Primary demyelination in transgenic mice expressing interferon-γ', Nature Medicine, vol. 3, no. 9, pp. 1037-1041. https://doi.org/10.1038/nm0997-1037
Horwitz MS, Evans CF, McGavern DB, Roriguez M, Oldstone MBA. Primary demyelination in transgenic mice expressing interferon-γ. Nature Medicine. 1997 Sep 1;3(9):1037-1041. https://doi.org/10.1038/nm0997-1037
Horwitz, Marc S. ; Evans, Claire F. ; McGavern, Dorian B. ; Roriguez, Moses ; Oldstone, Michael B.A. / Primary demyelination in transgenic mice expressing interferon-γ. In: Nature Medicine. 1997 ; Vol. 3, No. 9. pp. 1037-1041.
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