Susceptibility to Experimental Biliary Atresia is linked to Different Hepatic Gene Expression Profiles in Two Different Mouse Strains

Aims: Aim of this study was to compare hepatic gene expression during the development of experimental biliary atresia in two different mouse strains. Methods: Balb/c mice and C57Black/6 (Black/6) mice were infected with RRV postpartum, clinical signs of BA and survival were noted. Liver sections were assessed for CD3, CD4 and CD8 expression, and the hepatic virus load was determined. Second, mice of both strains were sacrificed three days after infection. Isolated hepatic RNA was subjected to gene expression analysis using Affymetrix Gene Chip MOE 430 2.0. Results: The incidence of BA was significantly lower in Black/6 mice compared to Balb/c mice (13.5% vs. 67%, p<0.05). The mean virus titers were higher in mice with BA compared to mice without BA. Different gene profiles three days after virus infection were noted, with differential expression of 201 genes, including those regulating apoptosis, nucleic acid binding, transport function and particularly the immune response (CCL2, toll-like receptor 3 (TLR 3), CD 14 antigen, CXCL 10 and CXCL 11). This correlated with a significant increase of CD4 positive cells only in Balb/c mice with BA compared to healthy mice (13.5 vs. 5.0; p<0.05). Black/6 mice did not exhibit any significant increase of CD3 or CD4 leukocytes despite cholestasis. Conclusions: The different susceptibility to experimental BA was associated with an increase of CD4 T-cells in the liver of Balb/c mice, which is linked to different gene profiles at the onset of bile duct obstruction.