βENaC-transgenic mice are a model for cystic fibrosis-like lung disease and early bronchiectasis

Cystic fibrosis (CF) is characterized by mucus obstructions and enlargement of the small airways. βENaC-transgenic mice are a model for CF-like disease. Recently, we observed a 20%-60% enlargement of the conducting airways in these mice at postnatal days 3-36. These findings are noteworthy because enlarged conducting airways are characteristic for bronchiectasis, a condition defined by irreversibly dilated bronchi. To address the presence of bronchiectasis, we compared βENaC-transgenic mice and wild-type littermates, at postnatal days 3-36. The lungs were imaged by synchrotron radiation-based X-ray tomographic microscopy (TOMCAT, SLS, Paul Scherrer Institute, Villigen, Switzerland), and analyzed by two different stereological approaches: a) the classical one, where we measured the ratio between diameters of the conducting airways and the adjacent pulmonary artery, and b) a novel approach assessing the ratio between the total volume of the bronchi and total volume of the adjacent pulmonary artery. Both analyses show the presence of early bronchiectasis in βENaC-transgenic mice at postnatal days 3, 10 and 21. However, at day 36, the enlargement of the conducting airways, in βENaC-transgenic mice, was accompanied by an over-proportional enlargement of the adjacent pulmonary arteries, resulting in the absence of bronchiectasis at this day, according to its common definition. This suggests the need for a revised definition of bronchiectasis in mice, as the airways exhibit all characteristics of this condition at day 36, despite the vascular enlargement. In conclusion, we propose the βENaC-transgenic mouse as a suitable model for early and potentially later stages of bronchiectasis.