Analysis of CNS Lymphatic Systems of C57BL/6 and SJL Mice Post-Infection With Theiler's Virus

Abstract

Theiler’s Murine Encephalomyelitis Virus (TMEV) infection is an important murine model for epilepsy and multiple sclerosis, however, it does not affect all mouse strains equally. SJL and C57BL/6 mice can both be infected with the BeAn strain of TMEV and experience the initial encephalitic phase. C57BL/6 mice develop seizures during the first week of infection and then clear the virus from the CNS, however, infected SJL mice do not develop seizures, are unable to clear the virus, and develop a chronic immune-mediated demyelinating disease similar to multiple sclerosis. One factor that may contribute to these different disease phenotypes may be the newly discovered CNS lymphatic system. To test this hypothesis, the two strains of mice will be infected with TMEV and comparisons will be made of the lymphatic systems found in the dura mater surrounding their brains. Expression of the chemoattractant CCL21 as well as the lymphatic system’s morphology will be observed through immunofluorescence microscopy to determine any differences. Any large differences between the two strains could help to elucidate why C57BL/6 mice are resistant to the demyelinating phase while SJL mice are not, a critical question in understanding the TMEV multiple sclerosis model.