MICROMouse Program Application Abstract
Effect of Murine norovirus on the phenotype of LDL Receptor-Deficient mice
Lillian Maggio-Price (Seattle, WA)
Murine norovirus (MNV) is endemic in many SPF mouse colonies across North America, creating significant potential for this virus to interfere with mouse models of human disease. This virus is related to the human Norwalk virus that causes gastrointestinal inflammation in humans. Although MNV does not cause any illness in normal mice, significant inflammation and mortality can be induced in mice with abnormal innate immunity. We are currently using a mutant mouse model with TGF? dysregulation (Smad3KO mouse) in which an inflammatory bacterial stimulus results in inflammation associated colon cancer. In our preliminary studies, we found that MNV accelerated and increased the severity of colon cancer induced by the bacterial organism Helicobacter bilis in these mice. One mechanism by which MNV may interfere with mouse models of inflammation is via alterations in macrophages. MNV is known to reside in macrophages and dendritic cells, and macrophage accumulation is observed in atherosclerotic plaques and adipose tissue in obesity. Thus, we plan to determine whether MNV can influence the development of obesity and atherosclerosis in an animal model, LDLR-/- mice fed a diabetogenic diet (high fat, high sucrose) or an atherogenic diet containing cholesterol. We will analyze severity and onset of phenotypic changes associated with atherosclerosis, diabetes and obesity in LDLR-/- mice infected with MNV in comparison to non-infected LDLR-/- mice fed the test diets. These data will provide critical guidance for the large community of researchers utilizing mouse models to study human diseases.
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