The D4Mit12 locus on mouse chromosome 4 provides susceptibility to both gamma-ray-induced and N-methyl-N-nitrosourea-induced thymic lymphomas.

Low-penetrance genes control different susceptibilities to gamma-ray-induced thymic lymphomas in mouse strains. Our previous genetic analyses with backcross mice between BALB/c and MSM strains and congenic lines localized one such gene near the D4Mit12 locus on chromosome 4. N-Methyl-N-nitrosourea (MNU) is a guanine base-alkylating agent and differs from gamma-radiation in its mechanism of mutagenic action. Accordingly, in this study, we examined whether or not the locus also provides susceptibility to MNU-induced thymic lymphomas using 84 offsprings derived from congenic mice for D4Mit12. Association analysis provided a suggestive linkage at D4Mit12 (P = 0.0075) and the linkage was sustained by the peak of likelihood ratio statistical values being at the same position as that for the gamma-ray-induced lymphomas. The results strongly suggest that the BALB/c allele near D4Mit12 is associated with susceptibility to lymphomas induced by two carcinogenic agents having different mechanisms of mutagenic action.