Reduced expression of ABCB4 is linked to an inflammatory phenotype of biliary atresia in mice and men

Purpose: to identify differentially regulated pathways and processes in the livers of neonatal Mdr+/- compared to Mdr+/+ mice and correlate these transcriptomics with hepatic lipdomics data Methods: Mdr2+/- mice were mated. There offspring with +/+, +/-, and -/- mdr2 genotypes were kept as litter mates until harvest of livers at 10 days of life. Lobe 1 and 2 were dissected and snap frozen in liquid nitrogen for subsequent RNA isolation and lipid extraction, respectively. RNA-seq libraries were prepared using Illumina TruSeq RNA prep kits and sequenced on the Illumina Hi-Seq 2000. Results: Approximately 20 million reads were mapped to the mm10 mouse genome build using attotations produced by the Ensembl project, which corresponded to 36,400 transcripts. Of these, over 600 transcripts exhibited differential regulation between Mdr+/+ and Mdr+/- samples. Conclusions: Our study supports a pro-inflammatory microenvironment in neonatal, non-infected mdr2+/- compared with wild type mice. Hepatic mRNA profiles of Mdr2+/+ and +/- neonatal, BALB/C mice were generated through RNAsequencing.研究目的：本研究旨在鉴定相较于Mdr+/+小鼠，新生Mdr+/-小鼠肝脏中差异调控的通路与生物学过程，并将该转录组学数据与肝脏脂质组学数据进行关联分析。 实验方法：通过交配构建Mdr2+/-小鼠，其子代携带+/+、+/-及-/- mdr2基因型的个体均以同窝方式饲养，直至出生后10天采集肝脏样本。分别解剖获取第1、2肝叶，将其于液氮中快速冷冻，分别用于后续RNA提取与脂质提取。采用Illumina TruSeq RNA建库试剂盒制备RNA-seq文库，并在Illumina Hi-Seq 2000测序平台上完成测序。 研究结果：依托Ensembl项目提供的基因组注释信息，约2000万条测序读段比对至mm10小鼠基因组版本，共对应36400个转录本。其中，超过600个转录本在Mdr+/+与Mdr+/-样本间呈现差异调控。 研究结论：本研究证实，相较于野生型小鼠，新生未感染的mdr2+/-小鼠肝脏存在促炎微环境。本研究通过RNA测序获取了BALB/C品系新生Mdr2+/+及+/-小鼠的肝脏mRNA表达谱。