Loss of TAZ after YAP deletion severely impairs foregut development and worsens cholestatic hepatocellular injury.

ABSTRACT:

Background

We previously showed that loss of yes-associated protein 1 (YAP) in early liver development (YAPKO) leads to an Alagille syndrome-like phenotype, with failure of intrahepatic bile duct development, severe cholestasis, and chronic hepatocyte adaptations to reduce liver injury. TAZ, a paralog of YAP, was significantly upregulated in YAPKO hepatocytes and interacted with TEA domain family member (TEAD) transcription factors, suggesting possible compensatory activity.

Methods

We deleted both Yap1 and Wwtr1 (which encodes TAZ) during early liver development using the Foxa3 promoter to drive Cre expression, similar to YAPKO mice, resulting in YAP/TAZ double knockout (DKO) and YAPKO with TAZ heterozygosity (YAPKO TAZHET). We evaluated these mice using immunohistochemistr

SUBMITTER: Gabdulkhakova A 

PROVIDER: S-EPMC10412434 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature