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

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 zeta-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 zeta-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.