ABCMdb

PMID: 11390493

Schroeder TH, Reiniger N, Meluleni G, Grout M, Coleman FT, Pier GB
Transgenic cystic fibrosis mice exhibit reduced early clearance of Pseudomonas aeruginosa from the respiratory tract.
J Immunol. 2001 Jun 15;166(12):7410-8., 2001-06-15 [PubMed]

Sentences

No. Mutations Sentence Comment

5 ABCC7 p.Ser489* We evaluated the role of CFTR in clearing P. aeruginosa from the respiratory tract using transgenic CF mice that carried either the ⌬F508 Cftr allele or an allele with a Cftr stop codon (S489X). Login to comment 6 ABCC7 p.Ser489* Intranasal application achieved P. aeruginosa lung infection in inbred C57BL/6 ⌬F508 Cftr mice, whereas ⌬F508 Cftr and S489X Cftr outbred mice required tracheal application of the inoculum to establish lung infection. Login to comment 47 ABCC7 p.Ser489* Transgenic CF mice included the following strains: C57BL/6 mice homozygous for the ⌬F508 allele of mouse Cftr (B6.129S6-Cftrttm1Kth ) (10), noninbred homozygous ⌬F508 Cftr mice (11), and doubly transgenic S489X Cftr-fatty acid binding protein (FABP)huCftr mice (no murine Cftr protein but expressing wild-type human (hu) CFTR protein in the gastrointestinal tract from the huCFTR gene under the control of the mouse FABP promoter) (12). Login to comment 48 ABCC7 p.Ser489* The doubly transgenic S489X Cftr-FABPhuCftr mice were bred as homozygotes. Login to comment 113 ABCC7 p.Ser489* Plating serial dilutions of the gastrointestinal organs and the nasopharyngeal anatomic area of intranasally infected S489X-FABPhuCftr mice revealed that the applied bacteria were not swallowed but remained in the nasopharynx of these transgenic CF mice (data not shown). Login to comment 122 ABCC7 p.Ser489* We first compared the total and internalized amount of bacteria in the lungs 4.5 h after tracheal infection of anesthetized wild-type C57BL/6 mice with that in two strains of transgenic CF mice: noninbred S489X FABPhuCftr mice and inbred B6.129S6-Cftrttm1Kth . Login to comment 123 ABCC7 p.Ser489* We found that lung cells of wild-type C57BL/6 mice internalized 7.6 times more P. aeruginosa PAO1 bacteria than did the C57BL/6 mice homozygous for the ⌬F508 Cftr allele (B6.129S6-Cftrttm1Kth mice) and 3.9 times more bacteria than did the S489X-FABPhuCftr mice ( p Ͻ 0.001, ANOVA and Fisher PLSD; Fig. 1A). Login to comment 125 ABCC7 p.Ser489* Coincident with the impaired internalization of P. aeruginosa in the respiratory tract of the two transgenic CF mouse strains, the total level of the infecting bacteria measured in the lungs was increased 22-fold in homozygous ⌬F508 Cftr C57BL/6 mice and 30-fold in S489X-FABPhuCftr mice, whereas in wild-type mice the increase in the bacterial burden over the inoculating dose was only 10-fold (Fig. 1B; both CF strains p Ͻ 0.01, ANOVA and Fisher PLSD compared with wild-type mice). Login to comment 134 ABCC7 p.Ser489* Chroneos et al. (7) recently reported that there was no difference in clearance of P. aeruginosa from the lungs of S489X-FABPhuCftr mice compared with wild-type mice. Login to comment 198 ABCC7 p.Ser489* Chroneos et al. (7) recently reported no difference in clearance of P. aeruginosa strain FRD-1 from the lungs of S489X-FABPhuCftr mice in comparison to wild-type mice, 24 h after a dose of 1.5 ϫ 107 CFU delivered intratracheally. Login to comment 204 ABCC7 p.Ser489* Chroneos et al. (7) also studied strain PAO1, as we did, but they only compared clearance between wild-type mice and double-transgenic S489X-FABPhuCftr mice that had been further engineered to overexpress huCFTR in the lungs under the control of the surfactant protein C (SP-C) promoter (SP-ChuCFTR mice). Login to comment 208 ABCC7 p.Ser489* For strain PAO1, Chroneos et al. (7) did not compare clearance in the transgenic S489X-FABPhuCFTR mice lacking CFTR in the lung with wild-type mice. Login to comment 263 ABCC7 p.Ser489* This occurred in both inbred and outbred transgenic mouse lines homozygous for the ⌬F508 allele of Cftr and in S489X Cftr-FABPhuCftr mice, which have no intact CFTR protein. Login to comment