title: Transgenic mouse model expressing P53(R172H), luciferase, EGFP, and KRAS(G12D) in a single open reading frame for live imaging of tumor.
abstract: Genetically engineered mouse cancer models allow tumors to be imaged in vivo via co-expression of a reporter gene with a tumor-initiating gene. However, differential transcriptional and translational regulation between the tumor-initiating gene and the reporter gene can result in inconsistency between the actual tumor size and the size indicated by the imaging assay. To overcome this limitation, we developed a transgenic mouse in which two oncogenes, encoding P53(R172H) and KRAS(G12D), are expressed together with two reporter genes, encoding enhanced green fluorescent protein (EGFP) and firefly luciferase, in a single open reading frame following Cre-mediated DNA excision. Systemic administration of adenovirus encoding Cre to these mice induced specific transgene expression in the liver. Repeated bioluminescence imaging of the mice revealed a continuous increase in the bioluminescent signal over time. A strong correlation was found between the bioluminescent signal and actual tumor size. Interestingly, all liver tumors induced by P53(R172H) and KRAS(G12D) in the model were hepatocellular adenomas. The mouse model was also used to trace cell proliferation in the epidermis via live fluorescence imaging. We anticipate that the transgenic mouse model will be useful for imaging tumor development in vivo and for investigating the oncogenic collaboration between P53(R172H) and KRAS(G12D).
authors.affiliation: 1] Liver Cirrhosis Clinical Research Center, Yonsei University College of Medicine, Seoul, Korea [2] Brain Korea 21 Project for Medical Science College of Medicine, Yonsei University, Seoul, Korea.
authors.forename: Hye-Lim
authors.initials: HL
authors.lastname: Ju
authors.affiliation: Institute of Pathology, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Diego F
authors.initials: DF
authors.lastname: Calvisi
authors.affiliation: 1] Liver Cirrhosis Clinical Research Center, Yonsei University College of Medicine, Seoul, Korea [2] Brain Korea 21 Project for Medical Science College of Medicine, Yonsei University, Seoul, Korea.
authors.forename: Hyuk
authors.initials: H
authors.lastname: Moon
authors.affiliation: 1] Liver Cirrhosis Clinical Research Center, Yonsei University College of Medicine, Seoul, Korea [2] Brain Korea 21 Project for Medical Science College of Medicine, Yonsei University, Seoul, Korea.
authors.forename: Sinhwa
authors.initials: S
authors.lastname: Baek
authors.affiliation: Institute of Pathology, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Silvia
authors.initials: S
authors.lastname: Ribback
authors.affiliation: Institute of Pathology, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Dombrowski
authors.affiliation: Liver Cirrhosis Clinical Research Center, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Kyung Joo
authors.initials: KJ
authors.lastname: Cho
authors.affiliation: 1] Liver Cirrhosis Clinical Research Center, Yonsei University College of Medicine, Seoul, Korea [2] Brain Korea 21 Project for Medical Science College of Medicine, Yonsei University, Seoul, Korea.
authors.forename: Sook In
authors.initials: SI
authors.lastname: Chung
authors.affiliation: 1] Liver Cirrhosis Clinical Research Center, Yonsei University College of Medicine, Seoul, Korea [2] Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Kwang-Hyub
authors.initials: KH
authors.lastname: Han
authors.affiliation: 1] Liver Cirrhosis Clinical Research Center, Yonsei University College of Medicine, Seoul, Korea [2] Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Simon Weonsang
authors.initials: SW
authors.lastname: Ro
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D004195:Disease Models, Animal; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D008156:Luciferases / Q000235:genetics / Q000378:metabolism*; D008163:Luminescent Measurements; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D041681:NIH 3T3 Cells; D016366:Open Reading Frames / Q000235:genetics; D061848:Optical Imaging; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D012867:Skin / Q000378:metabolism / Q000473:pathology; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D016159:Tumor Suppressor Protein p53; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D008156:Luciferases; D016283:Proto-Oncogene Proteins p21(ras)