RNA-seq analysis of proximal tubule specific Fan1 knockout transgenic kidneys subjected to cisplatin injury

FAN1 is a DNA endonuclease that we have previously identified as the underlying genetic cause of karyomegalic interstitial nephritis (OMIM: 614817) in humans. In order to deduce the molecular function of FAN1 in the setting of acute kidney injury and progression to chronic kidney disease, we generated a proximal tubule specific Fan1 knockout mouse model and subjected these mice to cisplatin injury. RNA-seq of the transgenic mice kidneys revealed dysregulation of the DNA damage repair pathway as well as cell cycle associated genes. Together, the data supports for a role of Fan1 in DNA damage repair, and that in its absence results in dysfunctional proximal tubule repair and regeneration upon cisplatin injury. 2X150 bp standard RNA-seq was performed using an Illumina HiSeq platform

FAN1是一种DNA核酸内切酶（DNA endonuclease），我们此前已证实其为人类巨核性间质性肾炎（karyomegalic interstitial nephritis，OMIM: 614817）的致病遗传根源。为阐明FAN1在急性肾损伤及慢性肾病进展过程中的分子功能，我们构建了近端小管特异性Fan1敲除小鼠模型，并对该模型小鼠施加顺铂（cisplatin）损伤处理。对转基因小鼠肾脏进行RNA测序（RNA-seq）后发现，DNA损伤修复通路及细胞周期相关基因均存在表达失调。综合上述数据，我们证实Fan1在DNA损伤修复中发挥功能；当其缺失时，会导致顺铂损伤后近端小管的修复与再生功能异常。本研究采用Illumina HiSeq平台完成了2×150 bp的标准RNA-seq测序。