Fall 2018 – Genetic Determinants of Virus Induced Neuropathology I

Infection with Theiler’s murine encephalomyelitis virus (TMEV) can cause various neurological conditions in mice which are similar to multiple sclerosis, epilepsy, amyotrophic lateral sclerosis, and Parkinson’s disease in humans. This makes TMEV an excellent tool for studying varied outcomes following viral infection, a phenomenon that occurs similarly in humans. The determinant of the outcome is the genetic makeup of the individual. Each of the responses to TMEV causes observable symptoms in mice, including altered gait. In this study, the specific area of interest is the effects of TMEV infection on the gait of different strains of Collaborative Cross mice. It was hypothesized that gait would be affected differently depending on the strain of mice and their genetic background. Infected and sham-infected (control) mice were studied over a period of 90 days, during which a number of gait parameters were measured three times using the DigiGait analysis system. The first of these gait measurements was taken pre-infection to be used as a baseline. A second data collection occurred ~21 days post-infection (dpi) and the final measurement was taken at ~90 dpi, just prior to sacrifice and tissue collection. We observed strain-specific differences in gait parameters as measured objectively via DigiGait. Additionally, we also observed differences between sexes in mice of the same strain for some parameters. In summary, gait differences are useful examples of how genetic background influences response to TMEV infection The students will be responsible for regularly checking mice (weighing and phenotyping), communicating with LARR personnel when cages or other equipment are needed, and assisting with: necropsies, organ collection and processing, RNA extractions, qPCR, RNAseq experiments and related activities (such as evaluating RNA quality), cytokine profiling experiments and related activities, data entry, and data interpretation as needed.