【进展】Identification of the Control Region of Pancreatic Expression of Bmp4 In Vitro a

Mayu Yasunaga1, Eiji Masui1, Asami Oji1, Atsumi Soma1, Mitsuhiko Osaki2,3, Tomoko Nakanishi1,3,
Kenzo Sato1,3*
1 Division of Molecular Biology, School of Life Sciences, Tottori University Faculty of Medicine, Yonago, Japan, 2 Division of Pathological Biochemistry, School of Life
Sciences, Tottori University Faculty of Medicine, Yonago, Japan, 3 Chromosome Engineering Research Center, Tottori University Faculty of Medicine, Yonago, Japan
Abstract
Bone morphogenetic protein 4 (Bmp4) was recently shown to be related to glucose homeostasis in mouse adult pancreas
through the regulation of insulin production. We previously revealed the predominant expression of Bmp4 in adult pancreas
by in vivo imaging of transgenic mice. However, the control regions for predominant Bmp4 expression in the adult pancreas
are unclear. In this study, we established transgenic (Tg) mice that allow real time in vivo bioluminescence imaging of the
enhancer/promoter activity of the Bmp4 gene. Tg mice expressing firefly luciferase with a 7 kb upstream region and 59-noncoding
sequence (three exons and two introns) of the Bmp4 gene showed pancreatic expression of bioluminescence, while
the Tg mice bearing luciferase with the 7 kb upstream region alone did not show pancreatic expression of the reporter
gene. Interestingly, pancreatic expression of bioluminescence was also present in Tg mice harboring the truncated
promoter without exon IA and IB, indicating the presence of a cryptic promoter in front of exon II. Furthermore, the
bioluminescence signal was not detected in embryonic pancreas, but increasing signals were observed in neonatal and
infantile Tg mice depending on the genotypes observed. These results suggested that a novel mechanism of transcription is
involved in pancreatic expression of the Bmp4 gene.
Citation: Yasunaga M, Masui E, Oji A, Soma A, Osaki M, et al. (2013) Identification of the Control Region of Pancreatic Expression of Bmp4 In Vitro and In
Vivo. PLoS ONE 8(4): e61821. doi:10.1371/journal.pone.0061821
Editor: Kathrin Maedler, University of Bremen, Germany
Received November 8, 2012; Accepted March 13, 2013; Published April 23, 2013
Copyright:
2013 Yasunaga et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This research was supported by a City Area Program (Basic Stage) from Ministry of Education, Culture, Sports, Science and Technology of Japan. The
funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: The authors have declared that no competing interests exist.
* E-mail: kensato@med.tottori-u.ac.jp