AN OBESITY LOCUS ON MOUSE CHROMOSOME 7

肥胖导致北方严重的发病率和死亡率 美国人口和有效的长期治疗并不是 可用。肥胖的病因是复杂的，既有遗传因素 易感和环境因素起作用。一种方法 加深我们对致病原因的了解 肥胖是为了识别基因并描述遗传机制。 导致了疾病的发生。对遗传机制的理解 导致肥胖的因素可能导致新的治疗方法的发展和 将有助于我们了解相关的环境因素造成的 肥胖。尽管在中国发现了导致一种复杂疾病的基因 人类种群是可能的，合适的老鼠模型提供了许多 优势包括近交系的可用性和丰富的遗传 资源。很可能与能量有关的相同途径 小鼠模型中的新陈代谢将与人类疾病有关。的确有 现在，来自多项不同研究的重要证据 独立实验室发现近端小鼠的一个遗传基因 7号染色体对小鼠体内脂肪的变化起到了作用。我们 在小鼠中使用辐射缺失突变体的初步数据 这表明该基因对身体脂肪有显著影响 内容，是家长式的印记，我们已经将其本地化到一个狭窄的 小鼠染色体上粉眼稀释点的远端区域 7.在本申请中，我们建议进一步缩小临界区域 使用一组额外的缺失突变体来包含该基因。我们 将绘制关键区域的物理图谱，绘制基因表达图谱 并评估位于该区域的候选基因的作用 在这张物理地图上。在这个项目结束时，我们将拥有 发现了一种有助于调节体内脂肪的基因 老鼠。后续资助期的后续研究将另行安排 致力于表征该基因的作用机制，并 确定它是否与人类肥胖有关。

Obesity results in significant morbidity and mortality in the North American population and effective long-term treatments are not available. The etiology of obesity is complex with both genetic predisposition and environmental factors playing a role. One approach to further our understanding of the causal factors responsible for obesity is to identify the genes and characterize the genetic mechanisms contributing to the disease. An understanding of the genetic mechanisms contributing to obesity may lead to new therapeutic developments and will help us to understand the relevant environmental factors causing obesity. Although finding genes contributing to a complex disease in human populations is possible, appropriate mouse models offer many advantages including the availability of inbred strains and rich genetic resources. It is likely that the same pathways involved in energy metabolism in mouse models will be involved in human disease. There is now significant evidence from a number of different studies in independent laboratories that a genetic locus on proximal mouse chromosome 7 is contributing to variation of body fat in the mouse. We have preliminary data using radiation deletion mutants in the mouse indicating that this gene is having a significant effect on body fat content, is paternally imprinted, and we have localized it to a narrow region just distal to the pink eyed dilution locus on mouse chromosome 7. In this application we propose to further narrow the critical region containing the gene using a panel of additional deletion mutants. We will physically map the critical region, develop a gene expression map for this area and evaluate the role of candidate genes which are located in this physical map. At the end of this project we will have identified a gene contributing to the regulation of body fat in the mouse. Follow-up studies in subsequent funding periods will be dir ected at characterizing the mechanism of action of this gene and determining if it is involved in human obesity.