Detection of the onset of ischemia and carcinogenesis by hypoxia-inducible transcription factor-based in vivo bioluminescence imaging.

An animal model for the early detection of common fatal diseases such as ischemic diseases and cancer is desirable for the development of new drugs and treatment strategies. Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that regulates oxygen homeostasis and plays key roles in a number...

Full description

Bibliographic Details
Main Authors: Tetsuya Kadonosono, Takahiro Kuchimaru, Shuichi Yamada, Yumi Takahashi, Atsushi Murakami, Taeko Tani, Hitomi Watanabe, Tomoharu Tanaka, Kiichi Hirota, Masahiro Inoue, Tetsuya Tsukamoto, Takeshi Toyoda, Koji Urano, Kazuhiko Machida, Tomoo Eto, Tomoyuki Ogura, Hideki Tsutsumi, Mamoru Ito, Masahiro Hiraoka, Gen Kondoh, Shinae Kizaka-Kondoh
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2011-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3213102?pdf=render
Description
Summary:An animal model for the early detection of common fatal diseases such as ischemic diseases and cancer is desirable for the development of new drugs and treatment strategies. Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that regulates oxygen homeostasis and plays key roles in a number of diseases, including cancer. Here, we established transgenic (Tg) mice that carry HRE/ODD-luciferase (HOL) gene, which generates bioluminescence in an HIF-1-dependent manner and was successfully used in this study to monitor HIF-1 activity in ischemic tissues. To monitor carcinogenesis in vivo, we mated HOL mice with rasH2 Tg mice, which are highly sensitive to carcinogens and are used for short-term carcinogenicity assessments. After rasH2-HOL Tg mice were treated with N-methyl-N-nitrosourea, bioluminescence was detected noninvasively as early as 9 weeks in tissues that contained papillomas and malignant lesions. These results suggest that the Tg mouse lines we established hold significant potential for monitoring the early onset of both ischemia and carcinogenesis and that these lines will be useful for screening chemicals for carcinogenic potential.
ISSN:1932-6203