| First Author | Johannesson B | Year | 2012 |
| Journal | PLoS One | Volume | 7 |
| Issue | 8 | Pages | e44059 |
| PubMed ID | 22937152 | Mgi Jnum | J:191673 |
| Mgi Id | MGI:5462300 | Doi | 10.1371/journal.pone.0044059 |
| Citation | Johannesson B, et al. (2012) CFTR regulates early pathogenesis of chronic obstructive lung disease in betaENaC-overexpressing mice. PLoS One 7(8):e44059 |
| abstractText | BACKGROUND: Factors determining the onset and severity of chronic obstructive pulmonary disease remain poorly understood. Previous studies demonstrated that airway surface dehydration in betaENaC-overexpressing (betaENaC-Tg) mice on a mixed genetic background caused either neonatal mortality or chronic obstructive lung disease suggesting that the onset of lung disease was modulated by the genetic background. METHODS: To test this hypothesis, we backcrossed betaENaC-Tg mice onto two inbred strains (C57BL/6 and BALB/c) and studied effects of the genetic background on neonatal mortality, airway ion transport and airway morphology. Further, we crossed betaENaC-Tg mice with CFTR-deficient mice to validate the role of CFTR in early lung disease. RESULTS: We demonstrate that the C57BL/6 background conferred increased CFTR-mediated Cl(-) secretion, which was associated with decreased mucus plugging and mortality in neonatal betaENaC-Tg C57BL/6 compared to betaENaC-Tg BALB/c mice. Conversely, genetic deletion of CFTR increased early mucus obstruction and mortality in betaENaC-Tg mice. CONCLUSIONS: We conclude that a decrease or absence of CFTR function in airway epithelia aggravates the severity of early airway mucus obstruction and related mortality in betaENaC-Tg mice. These results suggest that genetic or environmental factors that reduce CFTR activity may contribute to the onset and severity of chronic obstructive pulmonary disease and that CFTR may serve as a novel therapeutic target. |
