Detection of the Onset of Ischemia and Carcinogenesis by Hypoxia-inducible Transcription Factor-based in Vivo Bioluminescence Imaging

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2011 Nov 22

PMID 22102864

Citations 6

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

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

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A novel injectable BRET-based in vivo imaging probe for detecting the activity of hypoxia-inducible factor regulated by the ubiquitin-proteasome system.

Kuchimaru T, Suka T, Hirota K, Kadonosono T, Kizaka-Kondoh S Sci Rep. 2016; 6:34311.

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