Animal models for cystic fibrosis liver disease (CFLD)

Area of Science:

• Hepatology
• Genetics
• Microbiology

Background:

• Cystic Fibrosis (CF) liver disease (CFLD) is a severe complication of CF, a genetic disorder caused by CFTR gene mutations.
• The exact mechanisms leading to CFLD remain unclear, hindering the development of targeted treatments beyond UDCA.
• CFTR's role on cholangiocyte apical membranes, including chloride transport and immune regulation, is increasingly understood through CF animal models.

Purpose of the Study:

• To review and compare available Cystic Fibrosis (CF) animal models.
• To assess the applicability of these models for studying the liver phenotype in CF.
• To highlight advancements in understanding CFLD pathogenesis.

Main Methods:

• Review of existing literature on CF animal models.
• Comparison of CF mouse, pig, and ferret models regarding liver manifestation.
• Analysis of CFTR function and gut microbiota influence in CF liver disease.

Main Results:

• CF mice, while lacking spontaneous liver disease, have elucidated CFTR functions in cholangiocytes.
• Gut microbiota identified as a potential contributing factor to CFLD development.
• Novel CF models (pig, ferret) more closely mimic human disease, enabling comparative studies.

Conclusions:

• CF animal models have been crucial for understanding CFLD pathogenesis.
• Emerging models offer better platforms for studying CF liver disease and developing new therapies.
• Further research using advanced animal models is expected to yield novel therapeutic strategies for CFLD.