A Transgenic FOXJ1-Cre System for Gene Inactivation in Ciliated Epithelial Cells

Abstract

Ciliated airway epithelial cells are critical for mucosal barrier function, including host defense against pathogens. This cell population is often the primary target and thereby the first line of defense against many common respiratory viruses. It is also the precursor for mucous cells and thereby promotes mucociliary clearance of infectious and other noxious agents. Cells with motile cilia in other organs (e.g., brain and reproductive organs) may also have roles in development and reproduction. However, definitive proof of ciliated cell function is hampered by the lack of strategies to specifically target this cell population for loss of function in vivo. To this end, cell type-specific gene promoters have been combined with the Cre/LoxP system to disrupt genes in airway and alveolar epithelial cell populations expressing surfactant protein C (SP-C) or Clara cell secretory protein (CCSP). By contrast, an analogous system to disrupt gene function in ciliated airway epithelial cells was still needed. Here we report the generation and analysis of mouse lines with a FOXJ1 promoter driving the Cre recombinase and show that this system mediates genomic recombination specifically in ciliated cells. The pattern of recombination recapitulates endogenous FOXJ1 promoter function, being restricted to ciliated cells present in pulmonary airways as well as choroid plexus, ependyma, oviduct, and testis. This transgenic mouse system thereby offers a new strategy for specific knockouts of genes in ciliated cells. It should prove extremely useful for defining ciliated cell function in airway mucosal immunity as well as development and reproduction.

Canonical Notch signaling in the developing lung is required for determination of arterial smooth muscle cells and selection of Clara versus ciliated cell fate

“…Dermo1-Cre mice were generated by David Ornitz at Washington University, St Louis, MO (Yu et al, 2003). FOXJ1-Cre mice were a kind gift from Michael Holtzman, Washington University, St Louis, MO (Zhang et al, 2007). These mice were maintained on the CD1 background.…”

Evaluating the progenitor cells of ovarian cancer: analysis of current animal models

“…While a transgenic mouse expressing Cre recombinase under the FoxJ1 promoter demonstrates recombination within ciliated cells of the oviduct, recombination is also observed within bronchial cells (77). This model has not yet been crossed to mice carrying floxed alleles of genes relevant for serous cancer initiation, so it is unknown if gene inactivation specifically within the ciliated cells of the oviduct will lead to cancer formation.…”

Spatially Heterogeneous Choroid Plexus Transcriptomes Encode Positional Identity and Contribute to Regional CSF Production

“…The choroid plexi, located in each brain ventricle, consist of epithelial cells enveloping a stromal, fenestrated capillary network (Sturrock, 1979;Wilting and Christ, 1989). ChP epithelial cells secrete CSF, and tight junctions between cells form the blood-CSF barrier, preventing diffusion of systemic signals into CSF (Damkier et al, 2013).…”