Efficiency and Specificity of Gene Deletion in Lung Epithelial Doxycycline-Inducible Cre Mice

The transgenic mouse strains surfactant protein C–reverse tetracycline transactivator (SP-C-rtTA), club cell secretory protein (CCSP)-rtTA, and tetracycline operator (TetO)-Cre have been invaluable for spatiotemporally regulating gene deletion in the pulmonary epithelium. In this study, we measured the efficiency and specificity of gene deletion that can be achieved in these mice using the Rosa26-eYFP reporter. Triple-transgenic mice (tTg or rtTA/TetO-Cre/Rosa-eYFP) were bred and treated with various doxycycline (dox) regimens to induce gene deletion, which was then quantified in various cell populations by flow cytometry. In these crosses, we found that the TetO-Cre transgene must be transmitted through the female parent to avoid germline gene deletion. With dox exposure during lung development, SP-C-tTg mice deleted in ∼65–75% of alveolar epithelial type II (ATII) cells, but in only ∼45–50% of the integrin β4+ population, which consisted of club cells and distal lung progenitor cells. In contrast, CCSP-...