Intestinal expression of ASBT determines the sclerosing cholangitis phenotype.

Purpose: Determine the impact of ASBT genotype on the onset and progression of liver disease, using RNA-sequencing to characterize the transcriptome of ASBT wildtype and knockout mice. We assess alterations at the gene and mechanistic-levels. Methods: mRNA profiles were generated in 45-day-old ASBT WT and KO mice (BALB/cJ background). Data were processed using the Tuxedo Pipeline, using the mm10 genome with annotations provided by Ensembl. Results: We identified 1406 differentially expressed transcripts between knockout and wildtype mice, with ontologies heavily weighted toward fibrotic and inflammatory processes, with immune cell infiltration. Conclusions: Knockout of ASBT induces increased liver injury through exposure to elevated bile acids. We obtained caudate liver biopsies from mice aged 45 days following 2 weeks of high-fat breeder chow. We generated mRNA profiles according to standard Illumina protocols.