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Laboratory animals more than 100 million have consumed annually in laboratories for test of chemicals, medical devices, drugs and foods, and also have brought about a social problem in aspect of bioethics. Recently, bio-imaging system that can detect the fluorescence or bioluminescence signals in vivo, has considered as a replacement solution in the use of laboratory animals. Here, we tried to construct a mouse model with BRET(Bioluminescence Resonance Energy Transfer) system that is programmed to cut a recognizable site (DEVD amino acid sequence) by caspase-3 when the drug efficacy is observed. BRET expression vector was composed of a bioluminescent luciferase and a red fluorescent protein (tdTomato) under CAG promoter, and DEVD sequence was inserted between their proteins. Luciferase and tdTomato expressed normally in BRET-PC3 human prostatic cancer cells, and red fluorescence was observed under radiation- free status. During drug inducible apoptosis, bioluminescence rate catalyzed by luciferase rapidly increased whereas red fluorescent intensity decreased slightly. Next, BRET-PC3 cells injected into underskin in the femoral region to produce xenograft mouse model and were identified successfully expectable events occurred after treatment of apoptotic drugs like as BRET-PC3 cells. Finally, we constructed mouse expressing BRET system by microinjection and confirmed strong detectable signals using bio-imaging equipment. In this study, we developed a new mouse model with BRET system that can detect apoptotic reagents, and suggest the possibility as a teat model for drug discovery and development.