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Transgenic mouse model expressing P53(R172H), luciferase, EGFP, and KRAS(G12D) in a single open reading frame for live imaging of tumor

Authors
 Hye-Lim Ju  ;  Diego F. Calvisi  ;  Hyuk Moon  ;  Sinhwa Baek  ;  Silvia Ribback  ;  Frank Dombrowski  ;  Kyung Joo Cho  ;  Sook In Chung  ;  Kwang-Hyub Han  ;  Simon Weonsang Ro 
Citation
 SCIENTIFIC REPORTS, Vol.5 : 8053, 2015 
Journal Title
 SCIENTIFIC REPORTS 
Issue Date
2015
MeSH
Animals ; Cell Proliferation ; Disease Models, Animal ; Genes, Reporter ; Green Fluorescent Proteins/genetics ; Green Fluorescent Proteins/metabolism* ; Liver/metabolism ; Liver/pathology ; Liver Neoplasms/metabolism ; Liver Neoplasms/mortality ; Liver Neoplasms/pathology* ; Luciferases/genetics ; Luciferases/metabolism* ; Luminescent Measurements ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; NIH 3T3 Cells ; Open Reading Frames/genetics ; Optical Imaging ; Proto-Oncogene Proteins p21(ras)/genetics ; Proto-Oncogene Proteins p21(ras)/metabolism* ; Real-Time Polymerase Chain Reaction ; Skin/metabolism ; Skin/pathology ; Survival Rate ; Tumor Suppressor Protein p53/genetics ; Tumor Suppressor Protein p53/metabolism*
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).
Files in This Item:
T201500848.pdf Download
DOI
10.1038/srep08053
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
5. Research Institutes (연구소) > Institute of Gastroenterology (소화기병연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Ro, Simon Weonsang(노원상) ORCID logo https://orcid.org/0000-0003-2187-3698
Moon, Hyuk(문혁)
Chung, Sook In(정숙인) ORCID logo https://orcid.org/0000-0002-7915-9203
Cho, Kyuong Joo(조경주)
Ju, Hye Lim(주혜림)
Han, Kwang-Hyub(한광협) ORCID logo https://orcid.org/0000-0003-3960-6539
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/139741
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