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Alternative models have used either transgenic\n                      <jats:italic toggle=\"yes\">Scnn1b-Tg<\/jats:italic>\n                      mice overexpressing a lung epithelial sodium channel to mimic the mucus-rich CF lung environment, synthetic CF sputum medium (SCFM2) to induce bacterial phenotypes consistent with human CF, or agar beads to promote chronic infections by non-mucoid\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                      . Here, we combined these alternative models and established a chronic\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                      lung infection model using SCFM2 agar beads and\n                      <jats:italic toggle=\"yes\">Scnn1b-<\/jats:italic>\n                      Tg mice (SCFM2-\n                      <jats:italic toggle=\"yes\">Scnn1b-<\/jats:italic>\n                      Tg) to recapitulate nutrient and mucus characteristics of the human CF lung environment and test the effects of chronic infections on bacterial burden, lung function, and the immune response. Using wild-type SCFM2-C57BL\/6 mice as controls, SCFM2-\n                      <jats:italic toggle=\"yes\">Scnn1b-<\/jats:italic>\n                      Tg mice failed to clear bacterial infections, and lung function measurements showed that infected SCFM2-\n                      <jats:italic toggle=\"yes\">Scnn1b-<\/jats:italic>\n                      Tg mice had decreased inspiratory capacity and compliance, elevated airway resistance, and significantly reduced forced expiratory volumes. Flow cytometry and cytokine arrays showed that, like people with CF, SCFM2-\n                      <jats:italic toggle=\"yes\">Scnn1b-<\/jats:italic>\n                      Tg mice developed inflammation characterized by neutrophil and eosinophil infiltration and Th2 lymphocytic cytokine responses. Chronically infected SCFM2-\n                      <jats:italic toggle=\"yes\">Scnn1b-<\/jats:italic>\n                      Tg mice developed an exacerbated mix of innate and Th1, Th2, and Th17-mediated inflammation, causing higher lung cellular damage and elevated numbers of unusual Siglec F\n                      <jats:sup>+<\/jats:sup>\n                      neutrophils. SCFM2-\n                      <jats:italic toggle=\"yes\">Scnn1b-<\/jats:italic>\n                      Tg mice will be useful for investigating bacterial pathogenesis by non-mucoid\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                      , including treatments and the roles of Siglec F\n                      <jats:sup>+<\/jats:sup>\n                      neutrophils in CF inflammation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/iai.00230-25","type":"journal-article","created":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T09:48:14Z","timestamp":1749808094000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":12,"title":["A chronic\n                    <i>Pseudomonas aeruginosa<\/i>\n                    mouse lung infection modeling the mucus obstruction, lung function, and inflammation of human cystic fibrosis"],"prefix":"10.1128","volume":"93","author":[{"given":"Mylene","family":"Vaillancourt","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02pammg90","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center","place":["Los Angeles, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheryl E.","family":"Fernandes","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02pammg90","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center","place":["Los Angeles, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane","family":"Aguilar","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02pammg90","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biomedical Sciences, Cedars-Sinai Medical Center","place":["Los Angeles, 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