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

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 IL-2 constitutively (HSV-IL-2) causes CNS demyelination in different strains of mice. This model differs from most other models in that it represents a mixture of viral and immune triggers. In the present study, we directly compared MOG(35–55), MBP(35–47), and PLP(190–209) models of EAE with our HSV-IL-2-induced MS model. Mice with HSV-IL-2-induced and MOG-induced demyelinating diseases demonstrated a similar pattern and distribution of demyelination in their brain, spinal cord, and optic nerves. In contrast, no demyelination was detected in the optic nerves of MBP- and PLP-injected mice. IFN-β injections significantly reduced demyelination in brains of all groups, in the spinal cords of the MOG and MBP groups, and completely blocked it in the spinal cords of the PLP and HSV-IL-2 groups as well as in optic nerves of MOG and HSV-IL-2 groups. In contrast to IFN-β treatment, IL-12p70 protected the HSV-IL-2 group from demyelination, while 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.