Molecular phenotypes in early gallbladder and liver disease in the CFTR-/- sheep highlight aspects of CF-relevant hepatobiliary disease

However, enhanced longevity due to highly effective modulator therapies has generated renewed interest in key aspects of liver and gallbladder disease, and how these might be treated in people with CF (pwCF). To extend the CF hepatobiliary knowledgebase, we performed a transcriptomic analysis of liver and gallbladder development in the wild type (WT) and CFTR-/- sheep.

Bulk RNA was extracted from each tissue at specific timepoints through gestation (from 50 days to term) and used for RNA-seq. Differentially expressed genes between the timepoints within each genotype and between WT and CFTR-/- sheep at each timepoint were identified, and then used in gene ontology process enrichment analysis to reveal altered biological processes. We find that at the molecular level, the gallbladder in the CFTR-/- animals is both structurally and functionally compromised by mid-gestation, consistent with the observed microgallbladder phenotype.