International Mammalian Genome Society

logo18th International Mouse Genome Conference

17-22 October 2004, Seattle, USA


POSTER 42 - MODIFIER LOCI THAT INFLUENCE TPA SKIN TUMOR PROMOTION SUSCEPTIBILITY IN GENETIC CROSSES OF DBA/2 WITH C57BL/6 MICE

Angel JM, Abel EL, Riggs PK, Elizondo L, Caballero M, DiGiovanni J

Univ Texas, MD Anderson Cancer Center, Science Park-Research Division, Smithville, United States

Cancer susceptibility in the general population is a function of multiple, poorly penetrant modifier genes, each of which contributes to, but is not solely responsible for determining the likelihood that a particular type of cancer will develop after exposure to certain environmental carcinogenic agents.  Genetic differences in susceptibility to two-stage skin carcinogenesis in the mouse have been known for many years and the major contribution to susceptibility appears to be at the level of tumor promotion.  Loci that modify the susceptibility to 12-O-tetradecanoylphorbol-13-acetate (TPA) skin tumor promotion have been mapped to several chromosomal regions in genetic crosses of sensitive DBA/2 with relatively resistant C57BL/6 mice. One locus, Psl1, was mapped to an ~40 cM region of distal chromosome 9. Recent tumor studies using interval specific congenic mouse strains suggest that this region consists of at least three loci that modify the sensitivity to TPA skin tumor promotion.  A large number of genes mapping to these loci have been associated with skin phenotypes or cancer development. Additional studies using interval specific subcongenic strains and haplotype mapping are underway to further delimit the map locations of these loci. Furthermore, global gene expression analysis using cDNA microarrays have identified genes mapping to distal chromosome 9 that are differentially expressed in the epidermis of TPA-treated C57BL/6 vs DBA/2 mice, suggesting that these genes may be good candidates for TPA promotion susceptibility loci.

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