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Primary demyelination in transgenic mice expressing interferon-gamma
Marc S Horwitz1,2, Claire F Evans2, Dorian B Mcgavern3
1Departments of Immunology (IMM-23), 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Nature Medicine
|September 1, 1997
Summary
Interferon-gamma (IFN-gamma) directly induces central nervous system (CNS) demyelination and disease in a mouse model. This finding clarifies IFN-gamma's role in immune-mediated CNS disorders.
Area of Science:
- Neuroimmunology
- Molecular Biology
- Genetics
Background:
- The role of interferon-gamma (IFN-gamma) in central nervous system (CNS) demyelination is unclear, particularly after its use in multiple sclerosis (MS) treatment worsened disease.
- Investigating IFN-gamma's direct impact on demyelination is crucial for understanding immune-mediated CNS disorders.
Purpose of the Study:
- To determine the direct role of IFN-gamma in inducing CNS demyelination and disease.
- To establish a model for studying the mechanisms of IFN-gamma-mediated demyelination.
Main Methods:
- Generated transgenic mice expressing murine IFN-gamma cDNA in the CNS using an oligodendrocyte-specific promoter.
- Observed transgene expression in fully developed immune and CNS systems (after 8 weeks of age).
Main Results:
- Transgene expression was directly associated with primary demyelination and clinical signs of CNS disorders.
- Observed hallmarks of immune-mediated CNS disease: MHC molecule upregulation, gliosis, and lymphocytic infiltration.
Conclusions:
- IFN-gamma directly induces CNS demyelination and disease.
- This study provides a new model to investigate the mechanisms underlying demyelination in CNS disorders.
