RNA-Sequencing analysis of liver tissue from healthy WT mice and Foxa3-Cre YAP1 knockout mice at 3-4 months of age

We developed a mouse model of bile duct paucity by deleting Yes-associated protein 1 (YAP1) in foregut endoderm progenitors, using the Foxa3 promoter to drive Cre expression. YAP1 KO mice are viable postnatally and survive long-term despite a complete failure of intrahepatic bile duct development, resembling the liver phenotype of Alagille syndrome. We also observed no functional biliary regeneration over time. Adult YAP1 KO mice suffer from severe chronic cholestasis, but show minimal hepatocellular injury, suggesting that the hepatocytes have adapted to preserve liver function and reduce damage from the toxicity of bile acids and bilirubin. We used RNA-seq to analyze the gene expression patterns of whole liver tissue of adult YAP1 KO mice compared to WT, and found significant changes in metabolic activity, bile acid synthesis and transport that reflect hepatocyte reprogramming for survival. We analyzed 6 healthy liver tissue samples (3 male, 3 female) and 6 YAP1 KO liver tissue samples (3 male, 3 female).