In animal models, the existing CF mice do not represent the heterogeneity of the human population and are often lacking pulmonary phenotype. Recently a new mouse model, Collaborative Cross (CC) has been generated to overcome the limitation of existing resources. Thanks to a previous FFC project (FFC#11/2015), the existing CF F508del-/- mouse in C57Bl/6 background has been backcrossed in two CC murine lines, selected for their extreme genotypic and phenotypic diversity, that is the most susceptible (CC-S) and the most resistant (CC-R) to P. aeruginosa. Novel and unique CC-S-F508del-/- and CC-R-F508del-/- mice lines were generated. In this project, they will be characterized in the naïve status or after P. aeruginosa airway infection. Host defence, immune profile and molecular mechanisms against bacterial respiratory infections will be studied. Due to their high allelic diversity, these new mice models may reproduce diverse disease phenotypes (infection/inflammation), as observed in CF patients, offering a tool to better understand disease variability e to modulate and personalize CF therapies.