Next Article in Journal
Insights on Molecular Mechanisms of Chondrocytes Death in Osteoarthritis
Next Article in Special Issue
The HGF/SF Mouse Model of UV-Induced Melanoma as an In Vivo Sensor for Metastasis-Regulating Gene
Previous Article in Journal
Neuroprotection via Reduction in Stress: Altered Menstrual Patterns as a Marker for Stress and Implications for Long-Term Neurologic Health in Women
Article Menu
Issue 12 (December) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2016, 17(12), 2149; doi:10.3390/ijms17122149

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
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)
View Full-Text   |   Download PDF [1631 KB, uploaded 20 December 2016]   |  

Abstract

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
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary material

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

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.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top