Using a Reporter Mouse to Map Known and Novel Sites of GLP-1 Receptor Expression in Peripheral Tissues of Male Mice

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Using a Reporter Mouse to Map Known and Novel Sites of GLP-1 Receptor Expression in Peripheral Tissues of Male Mice. / Andersen, Daniel B.; Grunddal, Kaare V.; Pedersen, Jens; Kuhre, Rune E.; Lund, Mari L.; Holst, Jens J.; Ørskov, Cathrine.

In: Endocrinology, Vol. 162, No. 3, bqaa246, 2021.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Andersen, DB, Grunddal, KV, Pedersen, J, Kuhre, RE, Lund, ML, Holst, JJ & Ørskov, C 2021, 'Using a Reporter Mouse to Map Known and Novel Sites of GLP-1 Receptor Expression in Peripheral Tissues of Male Mice', Endocrinology, vol. 162, no. 3, bqaa246. https://doi.org/10.1210/endocr/bqaa246

APA

Andersen, D. B., Grunddal, K. V., Pedersen, J., Kuhre, R. E., Lund, M. L., Holst, J. J., & Ørskov, C. (2021). Using a Reporter Mouse to Map Known and Novel Sites of GLP-1 Receptor Expression in Peripheral Tissues of Male Mice. Endocrinology, 162(3), [bqaa246]. https://doi.org/10.1210/endocr/bqaa246

Vancouver

Andersen DB, Grunddal KV, Pedersen J, Kuhre RE, Lund ML, Holst JJ et al. Using a Reporter Mouse to Map Known and Novel Sites of GLP-1 Receptor Expression in Peripheral Tissues of Male Mice. Endocrinology. 2021;162(3). bqaa246. https://doi.org/10.1210/endocr/bqaa246

Author

Andersen, Daniel B. ; Grunddal, Kaare V. ; Pedersen, Jens ; Kuhre, Rune E. ; Lund, Mari L. ; Holst, Jens J. ; Ørskov, Cathrine. / Using a Reporter Mouse to Map Known and Novel Sites of GLP-1 Receptor Expression in Peripheral Tissues of Male Mice. In: Endocrinology. 2021 ; Vol. 162, No. 3.

Bibtex

@article{f927b36721f34072b350bbc7bf6bb4bc,
title = "Using a Reporter Mouse to Map Known and Novel Sites of GLP-1 Receptor Expression in Peripheral Tissues of Male Mice",
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.",
keywords = "glucagon-like peptide-1, glucagon-like peptide-1 receptor, reporter mouse",
author = "Andersen, {Daniel B.} and Grunddal, {Kaare V.} and Jens Pedersen and Kuhre, {Rune E.} and Lund, {Mari L.} and Holst, {Jens J.} and Cathrine {\O}rskov",
year = "2021",
doi = "10.1210/endocr/bqaa246",
language = "English",
volume = "162",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0013-7227",
publisher = "Oxford University Press",
number = "3",

}

RIS

TY - JOUR

T1 - Using a Reporter Mouse to Map Known and Novel Sites of GLP-1 Receptor Expression in Peripheral Tissues of Male Mice

AU - Andersen, Daniel B.

AU - Grunddal, Kaare V.

AU - Pedersen, Jens

AU - Kuhre, Rune E.

AU - Lund, Mari L.

AU - Holst, Jens J.

AU - Ørskov, Cathrine

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

KW - glucagon-like peptide-1

KW - glucagon-like peptide-1 receptor

KW - reporter mouse

U2 - 10.1210/endocr/bqaa246

DO - 10.1210/endocr/bqaa246

M3 - Journal article

C2 - 33508122

AN - SCOPUS:85100666671

VL - 162

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0013-7227

IS - 3

M1 - bqaa246

ER -

ID: 258082914