Figure 1. RB ablation results in sustained epithelial proliferation after injury.

Inducible RB ablation was targeted to the lung epithelium by mating CC10-rtTA and tetO-Cre double transgenic mice with RB^LoxP/LoxP mice (A). Pregnant dams were treated with doxycycline (circles) which activates rtTA (arches) expressed under control of the lung epithelial specific promoter. Activated rtTA induces Cre expression leading to recombination at LoxP sites flanking exon 19 in the RB gene locus. Hematoxylin and eosin stained sections of RB ablated and control adult lungs show similar overall morphology (B). Immunohistochemical analysis for Ki67 in RB ablated and control adult lungs from mice treated with doxycycline throughout gestation (C). The percent Ki67 positive cells (arrows) was comparable in RB ablated and control lungs before naphthalene treatment (Day 0) and at day 4 after injury (Day 4). A statistically significant increase in Ki67 positive cells was noted on day 4 as compared to day 0 in RB ablated (p=0.009) and control (p=0.011) lungs. In contrast, the percent Ki67 positive cells was significantly increased in RB ablated lungs versus controls on day 14 after injury (Day 14). Quantitative analysis is presented as average + SEM (D, *p=0.01). Data is representative of 5–7 animals per time point. br=bronchiole; Original magnification: 1000×