AN OBESITY LOCUS ON MOUSE CHROMOSOME 7

小鼠 7 号染色体上的肥胖位点

• 批准号: 2872253
• 负责人: David Brian West
• 金额: $ 26.23万
• 依托单位: UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-02-20 至 2002-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2872253
• 关键词: adipose tissue; animal genetic material tag; artificial chromosomes; body composition; chromosome deletion; chromosomes; computer assisted sequence analysis; gene expression; gene mutation; genetic mapping; heterozygote; laboratory mouse; molecular cloning; nucleic acid sequence; obesity; phenotype; plasmids; polymerase chain reaction; quantitative trait loci

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.

肥胖症导致北方的发病率和死亡率很高 美国人口和有效的长期治疗不是 available. 肥胖的病因是复杂的，既有遗传因素， 易感性和环境因素起作用。一种方法 以进一步了解导致 肥胖症是为了确定基因和特征的遗传机制 导致疾病。 对遗传机制的理解 导致肥胖可能导致新的治疗发展， 将帮助我们了解导致 肥胖虽然在人类中发现了导致复杂疾病的基因， 人类种群是可能的，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 资源 很可能与能量有关的相同途径 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表明， 独立的实验室， 7号染色体对小鼠体内脂肪的变异有贡献。 我们 在小鼠中使用辐射缺失突变体的初步数据 表明这种基因对身体脂肪有着重要的影响 内容，是父亲的印记，我们已经将其定位于一个狭窄的 小鼠染色体上粉红色眼睛稀释位点远端的区域 7. 在本申请中，我们提出进一步缩小临界区域 使用一组额外的缺失突变体含有该基因。我们 将绘制出关键区域的物理图谱， 并评估候选基因的作用， 在这张物理地图上。 在这个项目结束时，我们将有 确定了一个基因，有助于调节体内脂肪的调节， 老鼠. 在随后的资助期内， 在表征该基因的作用机制和 确定它是否与人类肥胖有关。