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AN OBESITY LOCUS ON MOUSE CHROMOSOME 7

小鼠 7 号染色体上的肥胖位点

基本信息

批准号：
6350690
负责人：
David Brian West
金额：
$ 27.76万
依托单位：
UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB
依托单位国家：
美国
项目类别：
财政年份：
1998
资助国家：
美国
起止时间：
1998-02-20 至 2004-07-31
项目状态：
已结题

项目摘要

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.

肥胖导致北方地区发病率和死亡率显着美国人口和有效的长期治疗并不可用的。肥胖的病因复杂，与遗传因素有关易感性和环境因素发挥作用。一种方法加深我们对造成这种情况的因果因素的理解肥胖是为了识别基因并表征遗传机制助长了这种疾病。了解遗传机制导致肥胖的因素可能会导致新的治疗方法的发展将有助于我们了解引起的相关环境因素肥胖。尽管发现了导致复杂疾病的基因人类群体是可能的，适当的小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基因资源。能量中可能涉及相同的途径小鼠模型中的代谢将参与人类疾病。有现在来自许多不同研究的重要证据独立实验室发现近端小鼠的遗传位点 7 号染色体导致小鼠体内脂肪的变化。我们使用小鼠辐射缺失突变体获得初步数据表明该基因对身体脂肪有显着影响内容，带有父系印记，我们将其本地化到一个狭窄的范围小鼠染色体上红眼稀释基因座远端的区域 7. 在这个应用中我们建议进一步缩小关键区域使用一组额外的缺失突变体包含该基因。我们将绘制关键区域的物理图谱，绘制基因表达图谱对于该区域并评估位于的候选基因的作用在这张物理图中。在这个项目结束时我们将得到发现了一个有助于调节身体脂肪的基因老鼠。后续资助期的后续研究将直接进行有助于表征该基因的作用机制和确定它是否与人类肥胖有关。