The progression and severity of pulmonary disease do not appear to correlate with the CFTR gene defect only. The host genetic background variability is known to determine different susceptibility to P. aeruginosa airway infection and related immune responsiveness. The existing CF mouse models do not represent the heterogeneity of the human population and are often lacking of pulmonary phenotype. Recently, a Collaborative Cross (CC) mouse was constructed having more recombination and genetic variation compared with that of other reference panels mouse population. Thus, this project will take advantage of unique CC mouse and existing CF ΔF508-/- mouse model to cross them and generate a new combined mouse model (CC and ΔF508-/-). It is expected to show different susceptibility to airway infection and thus to impact on different CF research areas.