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Transcriptomic analysis of the hypothalamic paraventricular and the arcuate nucleus of NNAT null mice

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Neuronatin (Nnat) has previously been reported to be part of a network of imprinted genes. Disruption of neuronatin results in an unusual phenotype of a bimodal body weight.In order to understand at the molecular level how the Nnat deficiency could contribute to the hypervariable phenotypes seen, we performed RNA sequencing from laser-capture micro dissected paraventricular nucleus (PVN) and arcuate nucleus (ARC) and compared the transcriptome between Nnat+/-p mice and their Nnat+/+ littermates in different feeding conditions. We performed an analysis of three subgroups: Nnat+/+ (all non-obese), Nnat+/-p non-obese, and Nnat+/-p obese mice and combined two approaches to identify differences in hypothalamic gene expression between subgroups Gene expression analysis between wild-type and NNAT null mice

神经元素(Neuronatin,Nnat)此前已被证实属于印迹基因(imprinted genes)网络的组成部分。神经元素的功能缺失会引发一种罕见的双峰体重表型。为从分子水平解析Nnat缺陷如何导致上述高度可变的表型,我们对激光捕获显微切割(laser-capture microdissected)获取的室旁核(paraventricular nucleus,PVN)与弓状核(arcuate nucleus,ARC)开展了RNA测序(RNA sequencing),并在不同喂养条件下,比较了Nnat+/-p小鼠与其野生型同窝仔鼠的转录组(transcriptome)差异。我们设置了三个亚组进行分析:全为非肥胖个体的Nnat+/+组、Nnat+/-p非肥胖组,以及Nnat+/-p肥胖组,并结合两种分析方法以鉴定各亚组间的下丘脑基因表达差异,以及野生型小鼠与NNAT敲除小鼠的基因表达分析。

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