Transgenic mouse model expressing P53R172H, luciferase, EGFP, and KRASG12D in a single open reading frame for live imaging of tumor

Hye Lim Ju, Diego F. Calvisi, Hyuk Moon, Sinhwa Baek, Silvia Ribback, Frank Dombrowski, Kyung Joo Cho, Sook In Chung, KwangHyub Han, Simon Weonsang Ro

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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 P53R172H and KRASG12D, 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 P53R172H and KRASG12D 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 P53R172H and KRASG12D.

Original languageEnglish
Number of pages1
JournalScientific reports
Volume5
DOIs
Publication statusPublished - 2015 Jan 1

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Luciferases
Transgenic Mice
Open Reading Frames
Neoplasms
Reporter Genes
Liver Cell Adenoma
Firefly Luciferases
enhanced green fluorescent protein
Liver
Optical Imaging
Transgenes
Oncogenes
Adenoviridae
Epidermis
Genes
Cell Proliferation
DNA

All Science Journal Classification (ASJC) codes

  • General

Cite this

Ju, Hye Lim ; Calvisi, Diego F. ; Moon, Hyuk ; Baek, Sinhwa ; Ribback, Silvia ; Dombrowski, Frank ; Cho, Kyung Joo ; Chung, Sook In ; Han, KwangHyub ; Ro, Simon Weonsang. / Transgenic mouse model expressing P53R172H, luciferase, EGFP, and KRASG12D in a single open reading frame for live imaging of tumor. In: Scientific reports. 2015 ; Vol. 5.
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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 P53R172H and KRASG12D, 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 P53R172H and KRASG12D 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 P53R172H and KRASG12D.",
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Transgenic mouse model expressing P53R172H, luciferase, EGFP, and KRASG12D in a single open reading frame for live imaging of tumor. / Ju, Hye Lim; Calvisi, Diego F.; Moon, Hyuk; Baek, Sinhwa; Ribback, Silvia; Dombrowski, Frank; Cho, Kyung Joo; Chung, Sook In; Han, KwangHyub; Ro, Simon Weonsang.

In: Scientific reports, Vol. 5, 01.01.2015.

Research output: Contribution to journalArticle

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AU - Ju, Hye Lim

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AU - Ribback, Silvia

AU - Dombrowski, Frank

AU - Cho, Kyung Joo

AU - Chung, Sook In

AU - Han, KwangHyub

AU - Ro, Simon Weonsang

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