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

开发和使用一种新型、易驯化的啮齿动物模型来研究冬眠代谢

• 批准号: 9146423
• 负责人: William James Israelsen
• 金额: $ 39.26万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9146423
• 关键词: American; Animal Model; Animals; Blood Glucose; Body Weight; Breeding; Charge; Chicago; Chiroptera; Collaborations; Communities; Computing Methodologies; Consensus; Data; Development; Diet; Eating; Emergency Medicine; Enzymes; Exhibits; Experimental Models; Fatty Liver; Fatty acid glycerol esters; Female; Foundations; Future; Gene Duplication; Gene Expression; Generations; Genes; Genetic Models; Genome; Glucose tolerance test; Goals; Health; Heart; Hibernation; Human; Immunoblotting; Insulin Resistance; Ketone Bodies; Laboratories; Liver; Mammals; Massachusetts; Medicine; Messenger RNA; Metabolic; Metabolic syndrome; Metabolism; Modeling; Mus; Obesity; Operative Surgical Procedures; Organ; Phenotype; Phosphorylation; Photoperiod; Post-Translational Protein Processing; Primates; Process; Protocols documentation; Pyruvate Kinase; Regulation; Research; Resources; Rodent; Rodent Model; Sampling; Seasons; Source; System; Techniques; Temperature; Testing; Time; Tissues; Ursidae Family; Weight Gain; Work; base; brain tissue; comparative genomics; design; drinking; follow-up; genome sequencing; glucose metabolism; insulin tolerance; metabolic abnormality assessment; metabolic rate; metabolomics; mouse genome; natural hypothermia; novel; pressure; programs; research study; transcriptome

 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.