cftr regulates early pathogenesis of chronic obstructive lung disease in βenac-overexpressing mice雌性生殖道调节早期的慢性阻塞性肺疾病发病机理βenac-overexpressing老鼠.pdfVIP

CFTR Regulates Early Pathogenesis of Chronic Obstructive Lung Disease in bENaC-Overexpressing Mice 1,3,4 1 1 1,3,4 1,2,4 Bjarki Johannesson , Stephanie Hirtz , Jolanthe Schatterny , Carsten Schultz , Marcus A. Mall * 1 Department of Translational Pulmonology, Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research, University of Heidelberg, Heidelberg, Germany, 2 Division of Pediatric Pulmonology and Allergy and Cystic Fibrosis Center, Department of Pediatrics III, University of Heidelberg, Heidelberg, Germany, 3 Cell Biology and Biophysics Unit, European Molecular Biology Laboratory, Heidelberg, Germany, 4 Molecular Medicine Partnership Unit, University of Heidelberg and European Molecular Biology Laboratory, Heidelberg, Germany Abstract Background: Factors determining the onset and severity of chronic obstructive pulmonary disease remain poorly understood. Previous studies demonstrated that airway surface dehydration in bENaC-overexpressing (bENaC-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 bENaC-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 bENaC-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 Cl2