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- Title
Independent genetic control of early and late stages of chemically induced skin tumors in a cross of a Japanese wild-derived inbred mouse strain, MSM/Ms.
- Authors
Okumura, Kazuhiro; Sato, Miho; Saito, Megumi; Miura, Ikuo; Wakana, Shigeharu; Mao, Jian-Hua; Miyasaka, Yuki; Kominami, Ryo; Wakabayashi, Yuichi
- Abstract
MSM/Ms is an inbred mouse strain derived from a Japanese wild mouse, Mus musculus molossinus. In this study, we showed that MSM/Ms mice exhibit dominant resistance when crossed with susceptible FVB/N mice and subjected to the two-stage skin carcinogenesis protocol using 7,12-dimethylbenz(a)anthracene (DMBA)/ 12-O-tetradecanoylphorbol-13-acetate (TPA). A series of F1 backcross mice were generated by crossing p53+/+ or p53+/– F1 (FVB/N × MSM/Ms) males with FVB/N female mice. These generated 228 backcross animals, approximately half of which were p53+/–, enabling us to search for p53-dependent skin tumor modifier genes. Highly significant linkage for papilloma multiplicity was found on chromosomes 6 and 7 and suggestive linkage was found on chromosomes 3, 5 and 12. Furthermore, in order to identify stage-dependent linkage loci we classified tumors into three categories (<2mm, 2–6mm and >6mm), and did linkage analysis. The same locus on chromosome 7 showed strong linkage in groups with <2mm or 2–6mm papillomas. No linkage was detected on chromosome 7 to papillomas >6mm, but a different locus on chromosome 4 showed strong linkage both to papillomas >6mm and to carcinomas. This locus, which maps near the Cdkn2a/p19Arf gene, was entirely p53-dependent, and was not seen in p53+/– backcross animals. Suggestive linkage conferring susceptibility to carcinoma was also found on chromosome 5. These results clearly suggest distinct loci regulate each stage of tumorigenesis, some of which are p53-dependent.
- Subjects
GENETICS; SKIN tumors; CARCINOGENESIS; TOLIDINE; ANTHRACENE; MUS
- Publication
Carcinogenesis, 2012, Vol 33, Issue 11, p2260
- ISSN
0143-3334
- Publication type
Article
- DOI
10.1093/carcin/bgs250