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- Title
Generation and Characterization of a Novel Mouse Model That Allows Spatiotemporal Quantification of Pancreatic β-Cell Proliferation.
- Authors
Tokumoto, Shinsuke; Yabe, Daisuke; Tatsuoka, Hisato; Usui, Ryota; Fauzi, Muhammad; Botagarova, Ainur; Goto, Hisanori; Herrera, Pedro Luis; Ogura, Masahito; Inagaki, Nobuya
- Abstract
Pancreatic β-cell proliferation has been gaining much attention as a therapeutic target for the prevention and treatment of diabetes. In order to evaluate potential β-cell mitogens, accurate and reliable methods for the detection and quantification of the β-cell proliferation rate are indispensable. In this study, we developed a novel tool that specifically labels replicating β-cells as mVenus+ cells by using RIP-Cre; R26Fucci2aR mice expressing the fluorescent ubiquitination-based cell cycle indicator Fucci2a in β-cells. In response to β-cell proliferation stimuli, such as insulin receptor antagonist S961 and diet-induced obesity (DIO), the number of 5-ethynyl-2'-deoxyuridine-positive insulin+ cells per insulin+ cells and the number of mVenus+ cells per mCherry+ mVenus- cells + mCherry- mVenus+ cells were similarly increased in these mice. Three-dimensional imaging of optically cleared pancreas tissue from these mice enabled quantification of replicating β-cells in the islets and morphometric analysis of the islets after known mitogenic interventions such as S961, DIO, pregnancy, and partial pancreatectomy. Thus, this novel mouse line is a powerful tool for spatiotemporal analysis and quantification of β-cell proliferation in response to mitogenic stimulation.
- Subjects
INSULIN receptors; THREE-dimensional imaging; MICE; MITOGENS; CELL cycle; ANIMAL experimentation; CELL physiology; COMPARATIVE studies; ANIMAL nutrition; GENES; ISLANDS of Langerhans; RESEARCH methodology; MEDICAL cooperation; OBESITY; PEPTIDES; RESEARCH; EVALUATION research
- Publication
Diabetes, 2020, Vol 69, Issue 11, p2340
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/db20-0290