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Article

Dermal Delivery of Constructs Encoding Cre Recombinase to Induce Skin Tumors in PtenLoxP/LoxP;BrafCA/+ Mice

1
Department of Immunology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
2
Department of Experimental Animal Pathology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
3
Division of Medical Oncology, Academic Medical Centre, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
4
Department of Medical Oncology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
*
Author to whom correspondence should be addressed.
Academic Editors: Andrzej Slominski, David M. Kaetzel and Marcus W. Bosenberg
Int. J. Mol. Sci. 2016, 17(12), 2149; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms17122149
Received: 28 October 2016 / Revised: 28 November 2016 / Accepted: 6 December 2016 / Published: 20 December 2016
(This article belongs to the Special Issue Animal Models of Melanoma)
Current genetically-engineered mouse melanoma models are often based on Tyr::CreERT2-controlled MAPK pathway activation by the BRAFV600E mutation and PI3K pathway activation by loss of PTEN. The major drawback of these models is the occurrence of spontaneous tumors caused by leakiness of the Tyr::CreERT2 system, hampering long-term experiments. To address this problem, we investigated several approaches to optimally provide local delivery of Cre recombinase, including injection of lentiviral particles, DNA tattoo administration and particle-mediated gene transfer, to induce melanomas in PtenLoxP/LoxP;BrafCA/+ mice lacking the Tyr::CreERT2 allele. We found that dermal delivery of the Cre recombinase gene under the control of a non-specific CAG promoter induced the formation of melanomas, but also keratoacanthoma and squamous cell carcinomas. Delivery of Cre recombinase DNA under the control of melanocyte-specific promoters in PtenLoxP/LoxP;BrafCA/+ mice resulted in sole melanoma induction. The growth rate and histological features of the induced tumors were similar to 4-hydroxytamoxifen-induced tumors in Tyr::CreERT2;PtenLoxP/LoxP;BrafCA/+ mice, while the onset of spontaneous tumors was prevented completely. These novel induction methods will allow long-term experiments in mouse models of skin malignancies. View Full-Text
Keywords: dermal delivery; CreERT2; melanoma dermal delivery; CreERT2; melanoma
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MDPI and ACS Style

Deken, M.A.; Song, J.-Y.; Gadiot, J.; Bins, A.D.; Kroon, P.; Verbrugge, I.; Blank, C.U. Dermal Delivery of Constructs Encoding Cre Recombinase to Induce Skin Tumors in PtenLoxP/LoxP;BrafCA/+ Mice. Int. J. Mol. Sci. 2016, 17, 2149. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms17122149

AMA Style

Deken MA, Song J-Y, Gadiot J, Bins AD, Kroon P, Verbrugge I, Blank CU. Dermal Delivery of Constructs Encoding Cre Recombinase to Induce Skin Tumors in PtenLoxP/LoxP;BrafCA/+ Mice. International Journal of Molecular Sciences. 2016; 17(12):2149. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms17122149

Chicago/Turabian Style

Deken, Marcel A., Ji-Ying Song, Jules Gadiot, Adriaan D. Bins, Paula Kroon, Inge Verbrugge, and Christian U. Blank 2016. "Dermal Delivery of Constructs Encoding Cre Recombinase to Induce Skin Tumors in PtenLoxP/LoxP;BrafCA/+ Mice" International Journal of Molecular Sciences 17, no. 12: 2149. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms17122149

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