| First Author | Grubb BR | Year | 2012 |
| Journal | Am J Physiol Lung Cell Mol Physiol | Volume | 302 |
| Issue | 2 | Pages | L238-47 |
| PubMed ID | 22003093 | Mgi Jnum | J:183328 |
| Mgi Id | MGI:5318422 | Doi | 10.1152/ajplung.00083.2011 |
| Citation | Grubb BR, et al. (2012) Transgenic hCFTR expression fails to correct beta-ENaC mouse lung disease. Am J Physiol Lung Cell Mol Physiol 302(2):L238-47 |
| abstractText | The relationships between airway epithelial Cl(-) secretion-Na(+) absorption balance, airway surface liquid (ASL) homeostasis, and lung disease were investigated in selected transgenic mice. 1) To determine if transgenic overexpression of wild-type (WT) human CFTR (hCFTR) accelerated Cl(-) secretion and regulated Na(+) absorption in murine airways, we utilized a Clara cell secretory protein (CCSP)-specific promoter to generate mice expressing airway-specific hCFTR. Ussing chamber studies revealed significantly ( approximately 2.5-fold) elevated basal Cl(-) secretory currents in CCSP-hCFTR transgenic mouse airways. Endogenous murine airway Na(+) absorption was not regulated by hCFTR, and these mice exhibited no lung disease. 2) We tested whether hCFTR, transgenically expressed on a transgenic mouse background overexpressing the beta-subunit of the epithelial Na(+) channel (beta-ENaC), restored ion transport balance and ASL volume homeostasis and ameliorated lung disease. Both transgenes were active in CCSP-hCFTR/beta-ENaC transgenic mouse airways, which exhibited an elevated basal Cl(-) secretion and Na(+) hyperabsorption. However, the airway disease characteristic of beta-ENaC mice persisted. Confocal studies of ASL volume homeostasis in cultured tracheal cells revealed ASL autoregulation to a height of approximately 6 mum in WT and CCSP-hCFTR cultures, whereas ASL was reduced to <4 mum in beta-ENaC and CCSP-hCFTR/beta-ENaC cultures. We conclude that 1) hCFTR overexpression increases basal Cl(-) secretion but does not regulate Na(+) transport in WT mice and 2) transgenic hCFTR produces increased Cl(-) secretion, but not regulation of Na(+) channels, in beta-ENaC mouse airways and does not ameliorate beta-ENaC mouse lung disease. |
