Mouse lung gene expression comparison between mesenchymal Flcn deletion and wild type control.

Loss of functional FLCN mutations are known to be the cause of Birt-Hogg-Dubé (BHD) syndrome, in which pulmonary cysts are presented in up to 90% of the patients. Lack of the related disease models in vivo poses a significant barrier to understanding the pathogenic mechanisms, including how the cysts develop and what molecular signaling pathways are involved. In this study, we selectively deleted Flcn specifically in lung mesenchymal cells using a Tbx4-rtTA/TetO-Cre driver. These mice exhibit defective postnatal lung alveolarization. Most strikingly, alveolar enlargement continues into adulthood in these mice, accompanied by bilateral pulmonary cyst formation that resemble human BHD. Interestingly, Flcn deletion in lung epithelial cells alone did not exhibit any alveolar enlargement. No synergistic or additive effects were detected in mouse lungs with combined Flcn deletion in both epithelial and mesenchymal compartments compared to the mice with lung mesenchymal Flcn knockout. We have compared differential gene expression of lung tissues between Flcn knockout in mesenchyme and wild type control mice by RNA-seq.