RNA-Sequencing analysis of liver tissue from female Foxa3-Cre YAP1 knockout mice, Foxa3-Cre YAP1 KO TAZ heterozygous mice, and WT littermate controls, at 3-4 months of age

ABSTRACT: 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. 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 next bred Foxa3-Cre YAP1 KO TAZ heterozygote and Foxa3-Cre YAP1 KO TAZ KO (DKO) mice to assess the role of TAZ in this model. DKO mice and male YAP KO TAZ heterozygotes died around time of birth. The survivors, YAP1 KO TAZ heterozygote females, were overall phenotypically similar to YAP1 KO mice, with absence of intrahepatic bile ducts and long-term survival. We used RNA-seq to analyze the gene expression patterns of whole liver tissue of female adult YAP1 KO mice compared to WT controls (C57BL/6 background), and female adult YAP1 KO TAZ heterozygote (YKTH) mice compared to WT controls (mixed C57BL/6 - FVB background). We found that both YAP1 KO and YAP1 KO TAZ heterozygote female mice were overall very similar and showed similar alterations in gene expression compared to WT. There were a few differences in pathways involved in cell cycling and monocyte recruitment.

ORGANISM(S): Mus musculus

PROVIDER: GSE213815 | GEO | 2023/07/20

REPOSITORIES: GEO