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A comparative study of experimental mouse models of central nervous system demyelination

Gene Therapy volume 21, pages 599–608 (2014)Cite this article

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Abstract

Several mouse models of multiple sclerosis (MS) are now available. We have established a mouse model, in which ocular infection with a recombinant HSV-1 that expresses murine interleukin (IL)-2 constitutively (HSV-IL-2) causes central nervous system demyelination in different strains of mice. This model differs from most other models, in which it represents a mixture of viral and immune triggers. In the present study, we directly compared MOG35–55, MBP35–47 and PLP190–209 models of experimental autoimmune encephalitis with our HSV-IL-2-induced MS model. Mice with HSV-IL-2- and myelin oligodendrocyte glycoprotein (MOG)-induced demyelinating diseases demonstrated a similar pattern and distribution of demyelination in their brain, spinal cord (SC) and optic nerves (ONs). In contrast, no demyelination was detected in the ONs of myelin basic protein (MBP)- and proteolipid protein (PLP)-injected mice. Interferon-β (IFN-β) injections significantly reduced demyelination in brains of all groups, in the SCs of the MOG and MBP groups, and completely blocked it in the SCs of the PLP and HSV-IL-2 groups as well as in ONs of MOG and HSV-IL-2 groups. In contrast to IFN-β treatment, IL-12p70 protected the HSV-IL-2 group from demyelination, whereas IL-4 was not effective at all in preventing demyelination. MOG-injected mice showed clinical signs of paralysis and disease-related mortality, whereas mice in the other treatment groups did not. Collectively, the results indicate that the HSV-IL-2 model and the MOG model complement each other and, together, provide unique insights into the heterogeneity of human MS.

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Acknowledgements

This work was supported by Public Health Service grants EY15557, EY13615 and AI093941. We thank Dr James M Markert of the Division of Neurosurgery, Department of Surgery, University of Alabama at Birmingham, for providing the M002 (HSV-IL-12p70) virus.

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  1. Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA, USA

    O M Dumitrascu

  2. Department of Surgery, Burns and Allen Research Institute, Cedars-Sinai Medical Center, Center for Neurobiology and Vaccine Development-D2066, Ophthalmology Research, Los Angeles, CA, USA

    K R Mott & H Ghiasi

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Dumitrascu, O., Mott, K. & Ghiasi, H. A comparative study of experimental mouse models of central nervous system demyelination. Gene Ther 21, 599–608 (2014). https://doi.org/10.1038/gt.2014.33

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