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. Overall design: Hepatic mRNA profiles of Mdr2+/+ and +/- neonatal, BALB/C mice were generated through RNAsequencing.

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Carey AN, Zhang W, Setchell KDR, Simmons JR, Shi T, Lages CS, Mullen M, Carroll K, Karns R, Bessho K, Sheridan R, Zhao X, Weber SN, Miethke AG