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Biological, cellular, and molecular characteristics of an inducible transgenic skin tumor model: a review

Oncogene volume 24, pages 8217–8228 (2005)Cite this article

Abstract

The genetically initiated Tg.AC transgenic mouse carries a transgene consisting of an oncogenic v-Ha-ras coding region flanked 5′ by a mouse ζ-globin promoter and 3′ by an SV-40 polyadenylation sequence. Located on chromosome 11, the transgene is transcriptionally silent until activated by chemical carcinogens, UV light, or full-thickness wounding. Expression of the transgene is an early event that drives cellular proliferation resulting in clonal expansion and tumor formation, the unique characteristics now associated with the Tg.AC mouse. This ras-dependent phenotype has resulted in the widespread interest and use of the Tg.AC mouse in experimental skin carcinogenesis and as an alternative carcinogenesis assay. This review examines the general biology of the tumorigenic responses observed in Tg.AC mice, the genetic interactions of the ras transgene, and explores the cellular and molecular regulation of ζ-globin promoted transgene expression. As a prototype alternative model to the current long-term rodent bioassays, the Tg.AC has generated a healthy discussion on the future of transgenic bioassays, and opened the doors for subsequent models for toxicity testing. The further exploration and elucidation of the molecular controls of transgene expression will enhance the usefulness of this mouse and enable a better understanding of the Tg.AC's discriminate response to chemical carcinogens.

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Acknowledgements

We dedicate this review to the memory of two valued friends and collaborators, Dr Ghanta N Rao and Dr Joel F Mahler, who have strongly contributed to the development and use of the Tg.AC mouse model. Dr Rao's dedication to the care and breeding of research animals, as well as his independent research and consultation, contributed to the high standard of quality that the Tg.AC mouse currently enjoys. Dr Mahler was instrumental in first describing, then exploring, the unique characteristics displayed not only by the Tg.AC mouse, but many other transgenic strains as well. His participation as pathologist and scientist considerably advanced our understanding of the biology and pathology of the Tg.AC mouse model. This work was partly funded by Grant NIEHS T32 ES07126 (MCH).

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  1. Curriculum in Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, 27514, NC, USA

    Michael C Humble

  2. National Center for Toxicogenomics, National Institute of Environmental Health Sciences, MD F1-05, 111 Alexander Drive, Research Triangle Park, PO Box 12233, 27709, NC, USA

    Michael C Humble, Carol S Trempus, Judson W Spalding, Ronald E Cannon & Raymond W Tennant

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Correspondence to Ronald E Cannon.

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Humble, M., Trempus, C., Spalding, J. et al. Biological, cellular, and molecular characteristics of an inducible transgenic skin tumor model: a review. Oncogene 24, 8217–8228 (2005). https://doi.org/10.1038/sj.onc.1209000

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