肥胖是现代社会面临的重大健康挑战，缺乏持久有效干预方法。肥胖小鼠模型选择有限，难以满足疾病机理和干预研究需要。我们发现一种未知功能G蛋白偶联受体(GPCR)突变小鼠显著肥胖，相关表型与常用肥胖小鼠品系存在差异，可望成为新的肥胖动物模型。作为GPCR家族的一员，该基因也有成为干预靶标的良好潜力。本项目将深入分析突变小鼠肥胖及相关表型的发生发展，掌握饮食等外界环境和不同遗传背景对表型的可能影响，分析突变小鼠肥胖的病理生理机制，探索该GPCR作为药物靶点的可行性和基因突变对人群肥胖的贡献。项目工作将鉴定一种新的肥胖动物模型，为进一步了解肥胖发生发展分子机制，寻找肥胖干预方法提供新的视角与线索。

Obesity is a rapidly increasing health threat related to cardiovascular diseases, diabetes, and cancer. Only small progresses have been achieved in efficient interference of overweight and obesity in modern society, due to the lack of mechanistic understanding of this process. Limited choices of animal models further delayed the study in the field. We found loss-of-function mutation of an orphan G protein-coupled receptor (GPCR) led to severe obesity in mice. The mutants exhibited different metabolic related phenotypes than popular obese mouse models, indicating the potential of this strain to act as a novel animal model of obesity. In addition, the nature of GPCR itself makes this protein a good candidate as therapeutic targets. We propose detailed characterization of development and progress of obesity and related phenotypes, as well as the effect brought by diet or different genetic backgrounds in the strain. We also propose analysis targeting pathphysiological mechanisms and potention contribution of GPCR mutations to human obesity. Finally, we propose to test the potential value of this GPCR as an obesity intervention target in transgenic mice. This study will establish a new animal model for obesity. It will also deepen our knowledge of the biological mechanisms underlying obesity, and provide new hints for disease intervention.