Establishment and characterization of a transgenic mouse model for in vivo imaging of Bmp4 expression in the pancreas.

Type-2 diabetes results from the development of insulin resistance and a concomitant impairment of insulin secretion. Bone morphogenetic protein 4 (Bmp4)-Bmp receptor 1A signaling in β cells has recently been reported to be required for insulin production and secretion. In addition, Bmp4 blocks the...

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Main Authors: Mayu Yasunaga, Nao Oumi, Mitsuhiko Osaki, Yasuhiro Kazuki, Tomoko Nakanishi, Mitsuo Oshimura, Kenzo Sato
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2011-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3174230?pdf=render
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author Mayu Yasunaga
Nao Oumi
Mitsuhiko Osaki
Yasuhiro Kazuki
Tomoko Nakanishi
Mitsuo Oshimura
Kenzo Sato
author_facet Mayu Yasunaga
Nao Oumi
Mitsuhiko Osaki
Yasuhiro Kazuki
Tomoko Nakanishi
Mitsuo Oshimura
Kenzo Sato
author_sort Mayu Yasunaga
collection DOAJ
description Type-2 diabetes results from the development of insulin resistance and a concomitant impairment of insulin secretion. Bone morphogenetic protein 4 (Bmp4)-Bmp receptor 1A signaling in β cells has recently been reported to be required for insulin production and secretion. In addition, Bmp4 blocks the differentiation and promotes the expansion of endocrine progenitor cells. Bmp4 therefore regulates the maintenance of homeostasis in the pancreas. In this study, we constructed a reporter plasmid carrying 7-kb enhancer and promoter region of the Bmp4 gene upstream of the firefly luciferase gene. We used this construct to produce transgenic mice by pro-nuclear microinjection, for subsequent in vivo monitoring of Bmp4 expression. The bioluminescent signal was detected mainly in the pancreas in three independent lines of transgenic mice. Furthermore, the bioluminescent signal was enhanced in association with the autophagy response to 24-h fasting. These results suggest that pancreatic expression of Bmp4 is involved in responding to the physiological environment, including through autophagy. These mouse models represent useful tools for toxicological screening, and for investigating the mechanisms responsible for pancreatic Bmp4 functions in vivo, with relevance to improving our understanding of pancreatic diseases.
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spelling doaj.art-d807bb9d421648cfbe1c09197ee9f6d82022-12-22T03:45:27ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0169e2495610.1371/journal.pone.0024956Establishment and characterization of a transgenic mouse model for in vivo imaging of Bmp4 expression in the pancreas.Mayu YasunagaNao OumiMitsuhiko OsakiYasuhiro KazukiTomoko NakanishiMitsuo OshimuraKenzo SatoType-2 diabetes results from the development of insulin resistance and a concomitant impairment of insulin secretion. Bone morphogenetic protein 4 (Bmp4)-Bmp receptor 1A signaling in β cells has recently been reported to be required for insulin production and secretion. In addition, Bmp4 blocks the differentiation and promotes the expansion of endocrine progenitor cells. Bmp4 therefore regulates the maintenance of homeostasis in the pancreas. In this study, we constructed a reporter plasmid carrying 7-kb enhancer and promoter region of the Bmp4 gene upstream of the firefly luciferase gene. We used this construct to produce transgenic mice by pro-nuclear microinjection, for subsequent in vivo monitoring of Bmp4 expression. The bioluminescent signal was detected mainly in the pancreas in three independent lines of transgenic mice. Furthermore, the bioluminescent signal was enhanced in association with the autophagy response to 24-h fasting. These results suggest that pancreatic expression of Bmp4 is involved in responding to the physiological environment, including through autophagy. These mouse models represent useful tools for toxicological screening, and for investigating the mechanisms responsible for pancreatic Bmp4 functions in vivo, with relevance to improving our understanding of pancreatic diseases.http://europepmc.org/articles/PMC3174230?pdf=render
spellingShingle Mayu Yasunaga
Nao Oumi
Mitsuhiko Osaki
Yasuhiro Kazuki
Tomoko Nakanishi
Mitsuo Oshimura
Kenzo Sato
Establishment and characterization of a transgenic mouse model for in vivo imaging of Bmp4 expression in the pancreas.
PLoS ONE
title Establishment and characterization of a transgenic mouse model for in vivo imaging of Bmp4 expression in the pancreas.
title_full Establishment and characterization of a transgenic mouse model for in vivo imaging of Bmp4 expression in the pancreas.
title_fullStr Establishment and characterization of a transgenic mouse model for in vivo imaging of Bmp4 expression in the pancreas.
title_full_unstemmed Establishment and characterization of a transgenic mouse model for in vivo imaging of Bmp4 expression in the pancreas.
title_short Establishment and characterization of a transgenic mouse model for in vivo imaging of Bmp4 expression in the pancreas.
title_sort establishment and characterization of a transgenic mouse model for in vivo imaging of bmp4 expression in the pancreas
url http://europepmc.org/articles/PMC3174230?pdf=render
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