Detection of the Onset of Ischemia and Carcinogenesis by Hypoxia-Inducible Transcription Factor-Based In Vivo Bioluminescence Imaging

作者：Kadonosono Tetsuya^*; Kuchimaru Takahiro; Yamada Shuichi; Takahashi Yumi; Murakami Atsushi; Tani Taeko; Watanabe Hitomi; Tanaka Tomoharu; Hirota Kiichi; Inoue Masahiro; Tsukamoto Tetsuya; Toyoda Takeshi; Urano Koji; Machida Kazuhiko; Eto Tomoo; Ogura Tomoyuki; Tsutsumi Hideki; Ito Mamoru; Hiraoka Masahiro; Kondoh Gen; Kizaka Kondoh Shinae

来源：PLos One, 2011, 6(11): e26640.

DOI：10.1371/journal.pone.0026640

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.

• 出版日期2011-11-10