CF animal models which recapitulate the genetic diversity, as hallmarks of the human population, have not been generated yet. Thus, the basic and translational studies in the CF field have been hindered by the lack of proper models which faithfully reproduce the human disease. This has left major questions on the pathogenesis and the possibilities available to properly test the efficacy of therapeutics. By leveraging the Collaborative Cross (CC) mice to recapitulate genotypic/phenotypic variations of the human population, researchers generated a new mouse model with the DelF508 CFTR mutation. This model exhibits major muco-obstructive alterations in the lungs and may answer several open questions regarding CF lung pathology. In this project, researchers will establish whether, how and to what extent the host genetic background: 1) affects the abundance and/or composition of airways mucus; 2) affects airways mucus through modulation of epithelial ion transport; 3) impacts airways mucus through alteration of the host microbiome. The ultimate goal is generating an adequate animal model for future studies aimed to new CF drug discovery.