Experiment
There are significant differencs in susceptibility to two-stage skin carcinogenesis. DBA/2 mice are relatively susceptible to skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate (TPA) while the C57BL/6 mice are resistant. To identify putative TPA-induced skin tumor susceptibility loci, 96 [(C57BL/6 x DBA/2)F1 x C57BL/6] backcross mice were analyzed in a study. An increase in TPA-induced skin tumor susceptibility was associated with the inheritance of DBA/2 alleles of distal Chromosome 9. Most significant associations were detected in D9Mit35, D9Mit53 and D9Mit51 (P = 0.023 and D9Mit20 (P = 0.017). To confirm this association, the authors determined the genotype of 96 (C57BL/6 x DBA/2)F2 intercross mice that had been characterized for their responsiveness to TPA-induced skin tumor promotion. Asssociation of genotype to TPA sensitivity was detected for D9Mit35 (P = 0.005), D9Mit53 (P = 0.008), D9Mit51 (P = 0.004) and D9Mit116 (P = 0.006) supporting the linkage of a TPA-induced skin tumor susceptibility locus to this region of Chromosome 9. In addition, the strain distribution pattern (SDP) of TPA-induced tumor promotion susceptibility in BXD recombinant inbred (RI) mice was compared to the SDP of other Chromosome 9 markers (see asssociated RI datain this paper). A significant association of TPA-induced tumor promotion susceptibility and genotype was detected for D9Mit51. The combined LOD equivalent scores obtained from the analysis of backcross, intercross and RI mice suggested linkage of a TPA-induced skin tumor susceptibility locus, Psl1, to D9Mit51 (LOD w = 4.1). Further analysis of F2 mice suggested that the locus also affected tumor multiplicity in addition to tumor susceptibilty. Possible candidate genes in this reion include Rbp2, Ryk, Ron, Hgfl and Tgfbr2.
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