CFTR regulates early pathogenesis of chronic obstructive lung disease in βenac-overexpressing mice

Bjarki Johannesson, Stephanie Hirtz, Jolanthe Schatterny, Carsten Schultz, Marcus A. Mall

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Background: Factors determining the onset and severity of chronic obstructive pulmonary disease remain poorly understood. Previous studies demonstrated that airway surface dehydration in βENaC-overexpressing (βENaC-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 βENaC-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 βENaC-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 βENaC-Tg C57BL/6 compared to βENaC-Tg BALB/c mice. Conversely, genetic deletion of CFTR increased early mucus obstruction and mortality in βENaC-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 βENaC-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.

Original languageEnglish (US)
Article numbere44059
JournalPLoS One
Volume7
Issue number8
DOIs
StatePublished - Aug 24 2012
Externally publishedYes

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Pulmonary diseases
respiratory tract diseases
Chronic Obstructive Pulmonary Disease
pathogenesis
neonatal mortality
mice
Infant Mortality
Mucus
mucus
genetic background
Inbred CFTR Mouse
Lung Diseases
Dehydration
Mortality
Ion Transport
Airway Obstruction
ion transport
Ions
Epithelium
epithelium

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

CFTR regulates early pathogenesis of chronic obstructive lung disease in βenac-overexpressing mice. / Johannesson, Bjarki; Hirtz, Stephanie; Schatterny, Jolanthe; Schultz, Carsten; Mall, Marcus A.

In: PLoS One, Vol. 7, No. 8, e44059, 24.08.2012.

Research output: Contribution to journalArticle

Johannesson, Bjarki ; Hirtz, Stephanie ; Schatterny, Jolanthe ; Schultz, Carsten ; Mall, Marcus A. / CFTR regulates early pathogenesis of chronic obstructive lung disease in βenac-overexpressing mice. In: PLoS One. 2012 ; Vol. 7, No. 8.
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