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Development of a flexible and specific gene delivery system for production of murine tumor models

Abstract

To develop models of human cancer we have expressed the avian retroviral receptor, TVA, under a variety of mammalian promoters in transgenic mice, thus rendering mice susceptible to infection with avian leukosis virus-derived gene vectors. TVA-based retroviral gene transfer offers advantages over current murine models of human cancer. A single transgenic mouse line can be used to evaluate multiple genetic lesions, individually and in combination. Furthermore, mutant genes are introduced somatically into animals, as occurs in the majority of naturally occurring tumors. Because the avian viral vectors replicate only in avian cells, the viral receptor in infected transgenic mouse cells remains available for multiple rounds of infection with different ASLV vectors. We discuss the theoretical and practical aspects of using recombinant avian retroviruses with TVA transgenic mice to generate cancer models.

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Acknowledgements

BC Lewis is a Helen Hay Whitney Foundation Post Doctoral Fellow, and Y Li is supported by the Army Breast Cancer Program. BO Williams was supported by a fellowship from the Cancer Research Fund of the Damon Runyon-Walter Winchell Foundation, and E Holland was supported by the Howard Hughes Medical Institutes Fellow Training Program.

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Fisher, G., Orsulic, S., Holland, E. et al. Development of a flexible and specific gene delivery system for production of murine tumor models. Oncogene 18, 5253–5260 (1999). https://doi.org/10.1038/sj.onc.1203087

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