Drosophila Model for Genetics of Obesity

肥胖遗传学果蝇模型

• 批准号: 7190464
• 负责人: SEYMOUR BENZER
• 金额: $ 4.86万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-20 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7190464
• 关键词: Drosophilidae; adipocytes; adipose tissue; biochemistry; body weight; circadian rhythms; developmental neurobiology; disease /disorder model; gene expression; gene mutation; genetic screening; genetic susceptibility; learning; memory; molecular cloning; obesity; phenotype; spectrometry

DESCRIPTION (provided by applicant): Obesity is a complex disorder caused by an imbalance between food intake and energy expenditure. These processes normally are precisely regulated, so that body weight can remain constant over a long time, in spite of variable food intake and activity. This homeostasis suggests the presence of strong regulatory mechanisms, and most biological mechanisms have an underlying genetic basis. The isolation of the Drosophila adipose mutation in the 1960's demonstrated that Drosophila can become obese, since that mutation causes a doubling in the overall fat content of adult flies. The strength of Drosophila as an experimental organism lies not only in its amenability to large scale, fast, and cheap genetic screening, but also in many years of genetic analysis, climaxing with the complete sequence of its genome, which makes it relatively easy to identify and clone genes with interesting mutant phenotypes. The list of biological problems for which Drosophila has been used successfully as a model is impressive, including the identification of genes that regulate the circadian rhythm, aspects of behavior such as learning and memory, and nervous system development. Many of these genes have provided clues to the discovery of their mammalian homologs. The use of Drosophila in obesity research opens the prospect of large-scale genetic screens to identify genes responsible for appetite control, body weight regulation, and fat storage, as well as analysis of the underlying biological mechanisms. We have isolated a series of obese mutants of Drosophila. The specific aims of the project will be to characterize their phenotypes, clone the genes, analyze the affected biochemical pathways, and isolate suppressor genes to reverse the genetic obesity defects.

描述（由申请人提供）： 肥胖是一种由食物摄入和能量消耗不平衡引起的复杂疾病。这些过程通常受到精确调节，因此尽管食物摄入量和活动量变化，体重仍可长期保持恒定。这种稳态表明存在强大的调节机制，并且大多数生物机制都有潜在的遗传基础。 20 世纪 60 年代分离出的果蝇脂肪突变表明，果蝇可以变得肥胖，因为这种突变会导致成年果蝇的总脂肪含量加倍。 果蝇作为实验生物的优势不仅在于其能够进行大规模、快速、廉价的基因筛查，还在于经过多年的基因分析，其基因组的完整序列使其相对容易识别并克隆具有有趣突变表型的基因。果蝇被成功用作模型的生物学问题清单令人印象深刻，包括调节昼夜节律的基因、学习和​​记忆等行为方面以及神经系统发育的基因的鉴定。其中许多基因为发现其哺乳动物同源物提供了线索。果蝇在肥胖研究中的应用开启了大规模遗传筛选的前景，以识别负责食欲控制、体重调节和脂肪储存的基因，并分析潜在的生物学机制。我们分离出一系列果蝇肥胖突变体。该项目的具体目标是表征其表型，克隆基因，分析受影响的生化途径，并分离抑制基因以逆转遗传性肥胖缺陷。