See the Historical Tumor Rates Controls for information on Tg.AC Heterozygous Transgenic Mice and p53 Heterozygous Mice.
The TG.AC transgenic line was produced in FVB/N mice by pronuclear injection of a v-Ha-ras transgene linked to a fetal zeta-globin promoter and an SV40 polyadenylation/splice sequence. TG.AC mice behave like genetically initiated mice, rapidly developing epidermal papillomas in response to topical tumor promoter or carcinogen treatment. In some experiments, the time to first tumor appearance has been as short as 3 weeks, but all chemicals tested that produced papillomas did so in less than 20 weeks. A dose-response relationship has been observed with promoters and carcinogens studied to date and in some studies mice have developed papillomas too numerous to count. In addition, TG.AC mice appear to respond to genotoxic as well as nongentotoxic carcinogens. While the response in treated mice is dramatic, it is important to note that untreated, singly housed TG.AC mice usually develop few, if any, spontaneous tumors and the histology of the skin is normal. With respect to mechanism, it has been shown that the v-Ha-ras transgene is not significantly expressed in non-tumor bearing TG.AC tissues but is over-expressed in the proliferating component of benign and malignant tumors. Thus, it appears that expression of the transgene drives proliferation and subsequent tumor development in carcinogen treated TG.AC skin.
Tennant, R.W., J.E. French & J.W. Spalding. (1995). Identification of chemical carcinogens and assessing potential risk in short-term bioassays using transgenic mouse models, Environ. Health Perspect., 103, 942-950.
Tennant, R.W., Spalding, J. & French,J.E. (1996). Evaluation of transgenic mouse bioassays for identifying carcinogens and noncarcinogens, Mutation Res. 365, 119-127.
This mouse model has an alteration of the p53 tumor suppressor gene, a gene critical to cell cycle control and DNA repair and one often found to be mutated or lost in human and rodent tumors. Mice with a single copy of the wildtype p53 allele (p53+/- heterozygous) offer a single target for mutagens, a condition analogous to humans with some heritable forms of cancer. The heterozygous state should increase the probability for either loss of p53 tumor suppressor function or gain of transforming activity by requiring only a single mutation. P53 heterozygous mice are viable and show a low background tumor incidence up to almost 12 months of age. Nullizygous (p53-/-)mice have a higher rate of spontaneous tumors at sites apparently determined by the mouse strain's genetic background.