Liver-restricted deletion of the biliary atresia candidate gene Pkd1l1 causes bile duct dysmorphogenesis and ciliopathy.

ABSTRACT:

Background and aims

A recent multicenter genetic exploration of the biliary atresia splenic malformation syndrome identified mutations in the ciliary gene PKD1L1 as candidate etiologic contributors. We hypothesized that deletion of Pkd1l1 in developing hepatoblasts would lead to cholangiopathy in mice.

Approach and results

CRISPR-based genome editing inserted loxP sites flanking exon 8 of the murine Pkd1l1 gene. Pkd1l1Fl/Fl cross-bred with alpha-fetoprotein-Cre expressing mice to generate a liver-specific intrahepatic Pkd1l1 -deficient model (LKO). From embryonic day 18 through week 30, control ( Fl/Fl ) and LKO mice were evaluated with standard serum chemistries and liver histology. At select ages, tissues were analyzed using RNA sequencing, immunofluorescence, and electron

SUBMITTER: Hellen DJ 

PROVIDER: S-EPMC12440248 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature