Functional Mx protein does not prevent experimental biliary atresia in Balb/c mice

Area of Science:

• Hepatology
• Virology
• Immunology

Background:

• Biliary atresia (BA) is a rare neonatal cholestatic liver disease with unknown etiology and poor outcomes.
• Mx proteins, mediators of innate antiviral immunity, are detected in human BA livers.
• The role of Mx protein in BA pathogenesis remains unclear.

Purpose of the Study:

• To investigate the effect of Mx protein expression on experimental biliary atresia (BA) in mice.
• To determine if Mx protein influences the course or incidence of RRV-induced BA in mice.

Main Methods:

• 185 newborn mice with functional (Balb/c-Mx+-A2G) or dysfunctional (Balb/c) Mx protein were infected with rhesus rotavirus (RRV) or saline.
• Mice were monitored for cholestasis signs and sacrificed at 3 weeks post-infection.
• Hepatic Mx protein expression and viral load were assessed using immunostaining and quantitative methods.

Main Results:

• No significant difference in BA incidence was observed between mice with functional and dysfunctional Mx protein (67% vs. 65%).
• High Mx protein expression was noted in mice with BA phenotype, irrespective of Mx protein functionality, but not in healthy controls.
• Hepatic viral load did not significantly differ between groups of mice with BA.

Conclusions:

• Mx protein does not prevent the development of RRV-induced BA in newborn mice.
• Mx protein expression in BA is independent of hepatic viral load.
• Mx protein shows potential as a biomarker for BA in both human and murine models.