Development and use of a novel, tractable rodent model for studies of hibernation metabolism

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 DESCRIPTION (provided by applicant): Hibernating mammals, including bears, bats, rodents, and at least one primate, undergo a period of rapid pre-hibernation weight gain, which allows them to build the fat reserves needed to survive up to 6 months of hibernation. During hibernation, the animals neither eat nor drink, but significantly suppresses its metabolic rate while using stored fat as the primary fuel source. A mechanistic understanding of hibernation could have an important impact on human medicine. Some of the adaptive metabolic states found in hibernators, such as pre-hibernation insulin resistance and fat accumulation, are similar to the maladaptive metabolic syndrome seen in humans, and an ability to create a hibernation-like state in humans could have a significant impact on emergency medicine, surgery or organ storage. However, the mechanisms underlying hibernation phenotypes remain largely unknown, and previous research efforts have been limited by the lack of tractable experimental models. This project will establish the meadow jumping mouse (Zapus hudsonius), a small North American hibernator, as a laboratory model of hibernation. Unlike current models, Zapus has a short generation time and it can be induced to hibernate using photoperiod and temperature regardless of outside season. The overall goals of this project are 1) to sequence and annotate the Zapus genome, and to compare the genome of Zapus with that of a closely related non-hibernator; 2) to establish a robust breeding colony and refine the conditions required to induce obesity and hibernation; and 3) to compare whole body and tissue-specific cellular metabolism in the summer-active, obese, and hibernating states, with a focus on regulation of glucose metabolism. This project is designed to establish the meadow jumping mouse as a tractable, genetic model of hibernation. The proposed metabolic characterization will advance the hibernation field by providing the first comprehensive view of hibernation metabolism. The long-term goal of this work is to lay the foundation for comprehensive study of the mechanisms of hibernation phenotypes, which may have important application to human health.