Two widely used activator lines—SPCrtTA (Sftpc-rtTA, line 1) and CCSPrtTA (Scgb1a1-rtTA, line 1)—enable researchers to activate transgenes in the distal and proximal lung epithelium of both embryonic and adult mice. These models have become essential tools in the lung biology community and are now used by hundreds of researchers worldwide.
To enable conditional gene deletion and lineage tracing, Dr. Perl generated tetO-Cre–based systems by crossing these rtTA drivers with tetO-Cre responder mice. Upon doxycycline administration, Cre recombinase is expressed in a tissue-specific manner, allowing precise deletion of floxed genes and permanent labeling of targeted cell lineages. The fidelity and localization of Cre activity were characterized using the Z/AP reporter system (Perl et al., PNAS, 2002).
This tetracycline-inducible Cre approach has become a cornerstone for lineage tracing and functional genomics in lung epithelial biology. For example, CCSPrtTA line 1 mediates recombination in the trachea, bronchi, bronchioles, and a subset of alveolar type II cells (Perl et al., Am J Respir Cell Mol Biol, 2005), while line 2 provides an alternative expression pattern (Perl et al., Am J Respir Crit Care Med, 2011).
All of these mouse lines are available through The Jackson Laboratory, facilitating broad use and reproducibility across the field.
In addition to generating these tools, Dr. Perl and Dr. Emma Rawlins co-authored the seminal review on inducible transgenic tools for the lung epithelium, fondly referred to as the “aMAZEing” review (PMID: 22180870), which provides guidance through the often complex landscape of transgenic strategies. More recently, the mesenchymal complexity of the lung was revisited and clarified in “The Elephant in the Lung” (PMID: 32442602), offering an updated view on fibroblast and mesenchymal lineage hierarchies.
Together, these contributions continue to support mechanistic discoveries in lung development, repair, and disease.
