Using a reporter mouse to map known and novel sites of GLP-1 receptor expression in peripheral tissues of male mice

DB Andersen, KV Grunddal, J Pedersen… - …, 2021 - academic.oup.com
DB Andersen, KV Grunddal, J Pedersen, RE Kuhre, ML Lund, JJ Holst, C Ørskov
Endocrinology, 2021academic.oup.com
Abstract Glucagon-like peptide-1 receptor (GLP-1R) activation is used in the treatment of
diabetes and obesity; however, GLP-1 induces many other physiological effects with unclear
mechanisms of action. To identify the cellular targets of GLP-1 and GLP-1 analogues, we
generated a Glp1r. tdTomato reporter mouse expressing the reporter protein, tdTomato, in
Glp1r-expressing cells. The reporter signal is expressed in all cells where GLP-1R promoter
was ever active. To complement this, we histologically mapped tdTomato-fluorescence, and …
Abstract
Glucagon-like peptide-1 receptor (GLP-1R) activation is used in the treatment of diabetes and obesity; however, GLP-1 induces many other physiological effects with unclear mechanisms of action. To identify the cellular targets of GLP-1 and GLP-1 analogues, we generated a Glp1r.tdTomato reporter mouse expressing the reporter protein, tdTomato, in Glp1r-expressing cells. The reporter signal is expressed in all cells where GLP-1R promoter was ever active. To complement this, we histologically mapped tdTomato-fluorescence, and performed Glp-1r mRNA in situ hybridization and GLP-1R immunohistochemistry on the same tissues. In male mice, we found tdTomato signal in mucus neck, chief, and parietal cells of the stomach; Brunner’s glands; small intestinal enteroendocrine cells and intraepithelial lymphocytes; and myenteric plexus nerve fibers throughout the gastrointestinal tract. Pancreatic acinar-, β-, and δ cells, but rarely α cells, were tdTomato-positive, as were renal arteriolar smooth muscle cells; endothelial cells of the liver, portal vein, and endocardium; aortal tunica media; and lung type 1 and type 2 pneumocytes. Some thyroid follicular and parafollicular cells displayed tdTomato expression, as did tracheal cartilage chondrocytes, skin fibroblasts, and sublingual gland mucus cells. In conclusion, our reporter mouse is a powerful tool for mapping known and novel sites of GLP-1R expression in the mouse, thus enhancing our understanding of the many target cells and effects of GLP-1 and GLP-1R agonists.
Oxford University Press