Figure 1

Creb1 deletion in developing lung epithelium and mesenchyme.
(a) Mechanism of respiratory-epithelial Creb1 deletion using a doxycyline-inducible triple transgenic mouse system. In the presence of Creb1fl, SPCrtTAtg and TetO-cretg alleles, doxycycline treatment induces lung-epithelial Cre recombinase expression. (b–d) Immunohistochemistry for Creb1 in Dox-treated E17.5 control (Creb1fl/fl; SPCrtTAtg/−) and Creb1EpKO lungs. Creb1 expression is virtually ubiquitous in control lungs (b) while lung epithelial Creb1 expression is mostly absent in Creb1EpKO lungs (c). Boxed area of (c) is magnified in (d) to show sporadic Creb1+ cells (arrows) in the Creb1EpKO proximal lung epithelium. (e–h) Creb1 immunohistochemistry in E17.5 (non Dox-treated) control, Creb1MesKO and Creb1fl−/− lungs. Control lungs show almost ubiquitous Creb1 expression (e) while mesenchymal Creb1 expression is mostly lost in Creb1MesKO lungs (f). Boxed area of (f) is magnified in (g) to show rare Creb1+ cells (arrows) in the Creb1MesKO lung mesenchyme. Creb1 expression is completely absent in Creb1fl−/− lungs (h). Dotted lines in (D) and (G) indicate the epithelial-mesenchymal boundary. ‘P’ indicates proximal airway lumen; ‘D’ indicates distal airway lumen. All images are representative of at least three animals per genotype. Scale bars: b,c,e,f,h; 90 μm.