Animal models of melanoma: a somatic cell gene delivery mouse model allows rapid evaluation of genes implicated in human melanoma

Abstract

The increasing incidence and mortality associated with advanced stages of melanoma are cause for concern. Few treatment options are available for advanced melanoma and the 5-year survival rate is less than 15%. Targeted therapies may revolutionize melanoma treatment by providing less toxic and more effective strategies. However, maximizing effectiveness requires further understanding of the molecular alterations that drive tumor formation, progression, and maintenance, as well as elucidating the mechanisms of resistance. Several different genetic alterations identified in human melanoma have been recapitulated in mice. This review outlines recent progress made in the development of mouse models of melanoma and summarizes what these findings reveal about the human disease. We begin with a discussion of traditional models and conclude with the recently developed RCAS/TVA somatic cell gene delivery mouse model of melanoma.

Figure 1.. Diagram of the RCAS/TVA melanoma mouse model and associated procedures. Expression of the TVA viral receptor is driven by the DCT promoter, which is expressed early in melanocyte development when cells are mitotically active. DCT-TVA mice are crossed with Ink4a/Arf^lox/lox mice to generate DCT-TVA–Ink4a/Arf^lox/lox mice. TVA negative mice are used as a control. Newborn mice are injected subcutaneously with viral producing cells, which are cleared by the host immune system within 1 week. Animals are monitored for tumor development, which is first observed after a latency of about 4 weeks. Melanocytes and tumors can be isolated and established in culture for further analysis. Images were produced by MediaLab at the Department of Biochemistry, University of Wisconsin at Madison.