Selection of candidate resistant (R) and susceptible (S) CC lines to P. aeruginosa infection was performed using a data sets, including survival rate, bacterial load and inflammatory response. By backcross breeding, the CFTR-F508del mutation have been introduced in two (R and S) CC backgrounds. Phenotypic characterization of CC lines showed that the host genetic diversity influences the progress and severity of P. aeruginosa airway infection. Based on these results, F508del of C57Bl/6 mice has been backcrossed into two CC lines with deviant phenotypes, resistant CC-R and susceptible CC-S mouse strains for airway disease. Two new CF mouse models were generated and will be used to study the role of the genetic background in the CF pathogenesis. Through the extension project (FFC#4/2017), researchers plan to analyze pathological mechanisms induced spontaneously or after infection by P. aeruginosa; inflammatory and microbiological profile will be studied and histopathology will be associated with quantitative analyses to highlight cellular and structural modifications in the lung.