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1 Department of Pediatrics, Case Western Reserve University, Cleveland, OH, USA
* To whom correspondence should be addressed. E-mail: amv2{at}cwru.edu.
Patients with cystic fibrosis have a lesion in the cystic fibrosis transmembrane conductance regulator gene (CFTR), which is associated with abnormal regulation of other ion channels, abnormal glycosylation of secreted and cell surface molecules, and vulnerability to bacterial infection and inflammation in the lung usually leading to the death of these patients. The exact mechanism(s) by which mutation in CFTR leads to lung infection and inflammation is not clear. Mice bearing different mutations in the murine homologue to CFTR (Cftr) (R117H, S489X, Y122X, and 
F508, all backcrossed to the C57BL/6J background) were compared with respect to growth and in their ability to respond to lung infection elicited with Pseudomonas aeruginosaladen agarose beads. Body weights of mice bearing mutations in Cftr were significantly smaller
than wild type mice at most ages. The inflammatory responses to P. aeruginosa-laden agarose beads were comparable in mice of all four Cftr mutant genotypes, with respect to absolute and relative cell counts in bronchoalveolar lavage fluid, and cytokine levels (TNF-
, IL-1
, IL-6, MIP-2, KC) and eicosanoid levels (PGE2 and LTB4) in epithelial lining fluid: the few small differences observed occurred only between cystic fibrosis mice bearing the S489X mutation and those bearing the knockout mutation Y122X. Thus, we cannot implicate either misprocessing of
CFTR or failure of CFTR to reach the plasma membrane in the genesis of the excess inflammatory response of CF mice. Therefore, it appears that any functional defect in CFTR
produces comparable inflammatory responses to lung infections with P. aeruginosa.
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