Mapping of melanoma modifier loci in RET transgenic mice

Transgenic mice carrying the RET oncogene under the control of the metallot hionein promoter exhibit severe pigmentation of the whole skin and melanocy tic tumors. The genetic background influences melanoma development in RET m ice; founder mice crossed with BALB/c mice show decreased incidence and inc reased latency of melanocytic tumors, whereas progeny of C57BL/6 mice show the opposite effect. Using partially congenic RET mice on a C57BL/6 genetic background (N3/RET mice), we studied genetic linkage in (N3/RETxBALB/c)xN3 /RET backcross mice. We mapped three melanoma modifier loci, on chromosome 1 (Melm1 and MElm2) and chromosome 11 (Melm3), that are linked with early m elanoma incidence and latency. Mapping of Melm loci and of five additional regions on chromosomes 6, 8, 9, 12, and 13 indicated allelic imbalance in N 3/RET mice, with a significant excess of BALB/c alleles, suggesting the pre sence of additional putative melanoma modifier loci on these chromosomes.