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Effect of combined deletions of ZFP36L1 and ZFP36L2 on gene expression in the mouse liver

ABSTRACT: RNA-binding proteins, Zinc Finger Protein 36 Like 1 (ZFP36L1) and Zinc Finger Protein 36 Like 2 (ZFP36L2), post-transcriptionally regulate the expression of genes involved in various cellular processes. Here, we show that the combined liver-specific loss of ZFP36L1 and ZFP36L2 in mice (L1/L2dKO) results in cholestatic liver injury as evidenced by the elevated hepatic and serum levels of total bile acids (TBA) and liver injury biomarkers, including ALP, ALT, and AST and characterized by the presence of bile infarcts followed by marked inflammation, cellular proliferation, and fibrosis. L1/L2dKO mice also showed reduced bile flow rate and decreased biliary TBA excretion. Subsequent analyses revealed impaired bile canalicular morphogenesis by postnatal day 7, as evidenced by F-actin and Zona Occludens-1 staining patterns. Additionally, RNA sequencing of whole liver samples of L1/L2dKO mice showed significant perturbation of ZFP36L1/ ZFP36L2 target genes associated with cholestasis, inflammation, fibrosis, and cell cycle. Overall, the study reveals critical beneficial roles of ZFP36L1 and ZFP36L2 in maintaining liver homeostasis.

ORGANISM(S): Mus musculus

PROVIDER: GSE299681 | GEO | 2026/03/11

REPOSITORIES: GEO

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