A transgenic FOXJ1-Cre system for gene inactivation in ciliated epithelial cells.
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.
Zhang
Yong
Y
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110-1093, USA.
Huang
Guangming
G
Shornick
Laurie P
LP
Roswit
William T
WT
Shipley
J Michael
JM
Brody
Steven L
SL
Holtzman
Michael J
MJ
D000818:Animals; D002923:Cilia / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000235:genetics*; D020869:Gene Expression Profiling; D020868:Gene Silencing; D006801:Humans; D019426:Integrases / Q000235:genetics*; D008168:Lung / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D011995:Recombination, Genetic / Q000235:genetics; D019076:Transgenes / Q000235:genetics*
C106349:FOXJ1 protein, human; D051858:Forkhead Transcription Factors; C045073:Cre recombinase; D019426:Integrases