Ribonomic dissection of LRb-expressing cells and neurons

描述（由申请人提供）：瘦素是一种脂肪细胞衍生的激素，通过结合和激活瘦素受体（LRb）的特定“长”异构体，向下丘脑发出身体能量储存状态的信号，LRb在下丘脑神经元的一个亚群中高度表达。通过这种方式，足够的瘦素水平发出能量补充的信号，抑制食欲，并允许能量昂贵的神经内分泌功能，如高代谢率、繁殖和生长。虽然表达LRb的神经元的基因组学对于理解瘦素调控的生理学和确定潜在的治疗靶点具有很大的兴趣，但只有一小部分下丘脑神经元表达LRb并对瘦素敏感。因此，下丘脑神经元混合群体中表达lrb的细胞的解剖和/或功能解剖是有问题的。该建议概述了一种以细胞类型特异性方式分离mRNA的新方法，并建立了瘦素反应性的细胞模型。这将使鉴定仅在表达lrb的细胞中表达的基因和分析这些细胞中受激素和营养调节的基因成为可能。通过这个过程，我们将能够生成治疗肥胖和其他神经内分泌疾病的潜在治疗靶点列表。

DESCRIPTION (provided by applicant): Leptin is an adipocyte-derived hormone that signals the status of body energy stores to the hypothalamus by binding and activating a specific "long" isoform of the leptin receptor (LRb) that is highly expressed in a subset of hypothalamic neurons. In this manner, adequate leptin levels signal energy repletion and serve to repress appetite and permit energy-expensive neuroendocrine functions, such as high metabolic rate, reproduction, and growth. While the genomics of LRb-expressing neurons are of great interest for the understanding of leptin-regulated physiology and for the identification of potential therapeutic targets, only a small percentage of hypothalamic neurons express LRb and are leptin-sensitive. Thus, the anatomic and/or functional dissection of LRb-expressing cells within the mixed population of hypothalamic neurons for genomic analysis is problematic. This proposal outlines a novel approach for isolating mRNA in a cell-type specific manner and development of a cellular model of leptin responsiveness. This will enable the identification of genes expressed only in LRb-expressing cells and the analysis of genes subject to hormonal and\or nutrient regulation in these cells. Through this process we will be able to generate a list of potential therapeutic targets for treatment of obesity and other neuroendocrine disorders.