New chemically induced skin tumour susceptibility loci identified in a mouse backcross between FVB and dominant resistant PWK

Abstract

Background: A variety of skin cancer susceptibility among mouse strains has allowed identification of genes responsible for skin cancer development. Fifteen Skts loci for skin tumour susceptibility have been mapped so far by using the two-stage skin carcinogenesis model [induced by 7.12-dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)]. A few responsible genes have been identified using wild-derived dominant resistant Mus spretus mice, and one has been confirmed as a low penetrance cancer susceptibility gene in a variety of human cancers.

New outbred colony derived from Mus musculus castaneus to identify skin tumor susceptibility loci

“…Five out of 20 FC F1 hybrid mice developed papillomas; however, all of the five had only one or two papillomas. In a study of 218 FVB and M. m. castaneus backcross mice, a significant QTL with a maximum LOD score of 14.4 was mapped on Chromosome 4, and that was overlapped with Skts‐fp1 , which has been mapped by analysis of the FVB and PWK cross 7.…”

“…The maximum linkage for papilloma multiplicity was observed between D4Mit289 (81.1 Mbp) and D4Mit165 (90.7 Mbp) and was overlapped with one of the two highest peaks of Skts‐fp1 , located between D4Mit289 (81.1 Mbp) and D4Mit153 (96.1 Mbp), which was mapped in the FVB and PWK cross 7. Another peak of around D4Mit146 (109.4 Mbp) in that cross was however, not observed in the linkage analysis of the FVB and M. m. castaneus backcross.…”

“…Mouse models of cancer have been extensively used for analysis of the genetic basis of tumor‐susceptibility, by which multiple cancer‐susceptibility loci have been mapped 3, 4. Susceptibility for the two‐stage skin carcinogenesis model varies among mouse strains 5, 6, and a genetic approach has been used to identify the specific loci related to differences in tumor‐susceptibility among the strains 3, 4, 7–9. Fifteen skin tumor‐susceptibility loci, Skts1–15 , were mapped by analyzing an NIH and Mus spretus cross, in which Mus spretus is dominant‐resistant against NIH 10, 11.…”

“…A Skts1 locus was also mapped by analyzing the Car‐R and Car‐S crosses 12, which were generated by the balanced intercross of eight inbred strains, including A/J, BALB/C, SJL/J, SWR/J, C57BL/6J, CBA/J, DBA/2, and P/J 5. Psl1–4 were mapped by using a C57BL/6J(B6) and DBA cross 13, 14, and Skts‐fp1–3 were mapped by using a PWK and FVB cross 7. Among them, only a limited number of corresponding genes for each locus has been identified.…”

Mapping of new skin tumor susceptibility loci by a phenotype‑driven congenic approach

“…Susceptibility to the two-stage skin carcinogenesis protocol varies among mouse strains (5,6), and genetic approaches have been used to identify the specific loci related to the differences in tumor susceptibility among strains (3,4,(7)(8)(9)(10)(11). For example, 15 skin tumor susceptibility loci, Skts1-15 have been mapped by analysis of NIH and Mus spretus cross, in which Mus spretus showed the dominant resistance against NIH (12,13).…”