Abstract
The alveolar region of the lung is composed of two major epithelial cell types: cuboidal alveolar type 2 cells (AT2 cells), which produce surfactant proteins, and large, thin, alveolar type 1 cells (AT1 cells), specialized for efficient gas exchange. AT1 cells cover more than 95% of the alveolar surface and constitute a major barrier to the entry of pathogenic agents. Relatively few genetic tools are available for studying the development of AT1 cells, the function of genes expressed in them, and the effect of specifically killing them in vivo in the adult lung. One distinguishing feature of AT1 cells is the high level of expression of the gene Ager, encoding the advanced glycation endproduct-specific receptor, a member of the immunoglobulin superfamily of cell surface receptors. In this paper, we report the generation of a novel Ager-CreERT2 allele in which Cre recombinase is inserted into the first coding exon of the endogenous gene. After treatment with tamoxifen the allele enables Ager+ progenitor cells to be efficiently lineage labeled during late embryonic development and AT1 cells to be killed in the adult lung using a Rosa26-diphtheria toxin A allele. Significantly, adult mice in which approximately 50% of the AT1 cells...Continue Reading
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