C. elegans Model for the Genetics of Adipogenesis

描述（由申请人提供）：我们的总体目标是阐明控制脂肪细胞发育和功能的机制。储存能量的能力，主要是脂肪，是一个迷人的特性，似乎是许多高等生物生命周期所必需的。不幸的是，脂肪积累的异常产生包括肥胖的病理状态，其正迅速成为全世界发病率和死亡率的主要原因之一。然而，调节脂肪细胞发育和生理的基因还没有完全了解。无脊椎动物已被证明是基因发现和表征基因功能的有力工具。因此，如果能有一个脂肪发育的无脊椎动物模型就太好了。我们有令人鼓舞的初步数据表明，C。线虫脂肪可能是这样一个模型，我们建议测试和利用这些初步观察。 具体的实验目的是：I.为了研究我们确定的C. elegans脂肪形成。我们将描述活蠕虫和哺乳动物系统中的基因。二.为了研究C.微阵列的脂肪。我们将比较野生型蠕虫和缺乏脂肪储存的蠕虫的表达谱。然后，我们将分析蠕虫和哺乳动物系统中的显着基因。伊利诺伊州为了鉴定C.通过反向和正向基因筛选，我们将通过RNAi和EMS诱变改变基因功能来产生缺乏脂肪的蠕虫。然后，我们将描述负责的基因。我们的长期目标是了解哺乳动物的脂肪形成，希望了解基因和机制可以导致合理和有效的治疗，以减轻与肥胖和糖尿病相关的痛苦。

DESCRIPTION (provided by applicant): Our overall objective is to elucidate the mechanisms that control adipocyte development and function. The ability to store energy, primarily as fat, is a fascinating property that seems to be required for the life cycle of many higher organisms. Unfortunately, abnormalities in fat accumulation produce pathological states including obesity, which is rapidly becoming one of the major causes of morbidity and mortality throughout the world. Yet, the genes that regulate adipocyte development and physiology are not fully understood. Invertebrates have proven to be powerful tools for gene discovery and for characterizing gene function. So, it would be great to have an invertebrate model for fat development. We have encouraging preliminary data that suggests that C. elegans fat might be such a model and we propose to test and exploit these initial observations. The specific experimental aims are: I. To study genes we identified as necessary for C. elegans fat formation. We will characterize the genes in both living worms and mammalian systems. II. To characterize the transcriptional profile of C. elegans fat with microarrays. We will compare the expression profiles of wild-type worms and worms that lack fat stores. Then, we will analyze the salient genes in worms and in mammalian systems. Ill. To identify genes required for formation of C. elegans fat via reverse and forward genetic screens. We will generate worms that lack fat by altering gene function with RNAi and with EMS mutagenesis. Then, we will characterize the responsible genes. Our long-term goal is to understand mammalian adipogenesis with the hope that understanding genes and mechanisms can lead to rational and effective treatments to relieve the suffering associated with obesity and diabetes.