Figure 1.

Overview of the approach taken to identify novel innate immune genes in mice. Morbidity and inflammatory (cytokine production in the serum) phenotypes were measured in 11 strains of mice. Strains were grouped based on phenotypes, and two-factor ANOVA analyses were performed to identify significantly differentially expressed genes between defined phenotypic groups (factor 1 in the ANOVA model) in response to lipopolysaccharide (LPS) compared with saline (factor 2 in the ANOVA model). Lists of differentially expressed genes were further analyzed to identify significantly overrepresented pathways or transcription factor binding sites. The involvement of the Hedgehog signaling pathway and the E2F1 transcription factor in innate immunity was validated using siRNA in a macrophage cell line and in mice with targeted deletions of the two genes.