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UBC Theses and Dissertations

Novel wild-derived mouse models of obesity and diabetes resistance Lee, Katie Ting Yan


Novel inbred mouse strains have been developed from wild-caught mice, and they display enhanced genetic diversity compared to the commonly used strains. We hypothesized that their unique genotypes may yield aspects of disease susceptibility previously unobserved in the commonly used strains. We examined two of these strains, PWD/PhJ (PWD) and WSB/EiJ (WSB), for obesity and type 2 diabetes (T2D)-related traits in response to high fat diet (HFD) feeding and compared them to the C57BL/6J (B6) strain. We identified PWD mice as a model of primary hyperinsulinemia. They had increased insulin levels at a young age while they were lean and insulin sensitive. They were protected from early development of diet-induced obesity, although they later developed obesity similar to B6 mice that may be induced by chronic hyperinsulinemia. PWD mice are a novel model of primary hyperinsulinemia as a cause of obesity. WSB mice are a model of extraordinary resistance to HFD-associated obesity and T2D. They have a higher energy expenditure that may have contributed to their protection from HFD-induced obesity. PWD and WSB mice modeled novel aspects of disease susceptibility and are interesting models for further study to determine the mechanisms associated with the pathogenesis of obesity and T2D.

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