The progression of liver fibrosis in response to chronic injury varies 
considerably among individual patients. The underlying genetics is highly 
complex due to large numbers of potential genes, environmental factors and cell 
types involved. Here, we provide the first toxicogenomic analysis of liver 
fibrosis induced by carbon tetrachloride in the murine 'genetic reference panel' 
of recombinant inbred BXD lines. Our aim was to define the core of risk genes 
and gene interaction networks that control fibrosis progression. Liver fibrosis 
phenotypes and gene expression profiles were determined in 35 BXD lines. 
Quantitative trait locus (QTL) analysis identified seven genomic loci 
influencing fibrosis phenotypes (pQTLs) with genome-wide significance on 
chromosomes 4, 5, 7, 12, and 17. Stepwise refinement was based on expression QTL 
mapping with stringent selection criteria, reducing the number of 1,351 
candidate genes located in the pQTLs to a final list of 11 cis-regulated genes. 
Our findings demonstrate that the BXD reference population represents a powerful 
experimental resource for shortlisting the genes within a regulatory network 
that determine the liver's vulnerability to chronic injury.