RNA-Seq analysis of the cystic fibrosis rat small intestine

Background: A recently developed animal model of the genetic disease is the cystic fibrosis (CF) rat, which similar to other animal models of CF exhibits a lethal intestinal phenotype. To begin characterizing the CF rat intestinal phenotype, we investigated global gene expression in the CF rat small intestine. Methods: Total RNA was extracted from full thickness of the entire small intestines of wild type (WT) and CF rats just before weaning. Results: There were 890 genes with significantly different expression levels (1.2-fold cutoff) comparing CF to wild type (WT), including 485 genes increased and 405 decreased in the CF intestine. The major pathways associated with these changes were inflammation, lipid metabolism, cytochrome P450-mediated degradative pathways, and cell growth/death. Comparison of the rat RNA-Seq dataset to earlier microarray analysis using a CFTR knockout mouse showed significant overlap with the CF rat small intestine. Conclusions: The small intestine of the new CF rat model exhibits numerous alterations in gene expression similar to other animal models of CF which indicate this will be an additional new model to study the gut effects CF.背景：新近开发的遗传性疾病动物模型为囊性纤维化（cystic fibrosis, CF）大鼠，其与其他CF动物模型类似，均表现出致死性肠道表型。 方法：于断奶前，从野生型（wild type, WT）及CF大鼠的完整小肠全层组织中提取总RNA。 结果：相较于野生型大鼠，CF大鼠肠道中有890个基因的表达水平存在显著差异（差异阈值为1.2倍），其中485个基因在CF大鼠肠道中表达上调，405个基因表达下调。与这些表达变化相关的主要通路包括炎症反应、脂质代谢、细胞色素P450介导的降解通路以及细胞生长/死亡通路。将本大鼠RNA测序（RNA-Seq）数据集与早期针对CFTR敲除小鼠的微阵列分析结果进行比对后发现，二者在CF大鼠小肠的表达谱中存在显著重叠。 结论：新型CF大鼠模型的小肠存在大量基因表达改变，与其他CF动物模型的表现相似，这表明该模型可作为研究囊性纤维化肠道效应的又一新型动物模型。