At least four genes and sex are associated with susceptibility to urethane-induced pulmonary adenomas in mice

Abstract

SummarySusceptibility to urethane-induced lung adenomas in mice has a polygenic mode of inheritance, with no obvious discontinuity in lung tumour counts among 37 AXB recombinant inbred strains. However, mean tumour counts were markedly higher in strains carrying the A/J allele at theKras2andH2complex than in those carrying the C57BL/6 allele. In 162 F2hybrids and small numbers of both backcrosses between strain A/J (susceptible) and C57BL/6 (resistant) mice, five factors influencing susceptibility were identified. Variation due to the ‘major’Kras2locus (chromosome 6) accounted for 60% of the total variation. ‘Minor’ loci linked to microsatellite markersTnfb(in theH2complex),D9Mit11andD19MH16(on chromosomes 17, 9 and 19, respectively) accounted for a further 13% of the variation, and males had more tumours than females with sex differences accounting for 2% of the variation. No significant association with 32 other loci was detected. On a square-root transformed scale, heterozygotes at all marker loci were of intermediate susceptibility compared with homozygotes. Thethree minor loci and sex only affected lung tumour counts when at least one susceptibleKras2allele was present.