Ager-CreERT2: A New Genetic Tool for Studying Lung Alveolar Development, Homeostasis, and Repair.

Ager-CreERT2: A New Genetic Tool for Studying Lung Alveolar Development, Homeostasis, and Repair. Am J Respir Cell Mol Biol. 2018 Jul 16;: Authors: Chung MI, Hogan BLM Abstract The alveolar region of the lung is composed of two major epithelial cell types; cuboidal Type 2 cells (AT2s), that produce surfactant proteins, and large, thin, Type1 cells (AT1s), specialized for efficient gas exchange. AT1s cover more than 95% of the alveolar surface and so constitute a major barrier to the entry of pathogenic agents. Relatively few genetic tools are available for studying the development of AT1s, the function of gene 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 Advanced Glycation End-product specific Receptor, a member of the immunoglobulin superfamily of cell surface receptors. Here, 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 about 50% of the AT1s are killed survive the loss; repair is associated with increased proliferation of Sftpc+ AT2s ...
Source: Am J Respir Cell Mol... - Category: Respiratory Medicine Authors: Tags: Am J Respir Cell Mol Biol Source Type: research