AT LEAST 4 LOCI AND GENDER ARE ASSOCIATED WITH SUSCEPTIBILITY TO THE CHEMICAL INDUCTION OF LUNG ADENOMAS IN A J X BALB/C MICE/

Four putative quantitative trait loci (QTLs) that influence susceptibi lity to the induction of lung adenomas by urethane in an F-2 cross bet ween A/J and BALB/cOlaHsd have been mapped. Following microsatellite t yping of mice with resistant and susceptible phenotypes at 97 microsat ellite marker loci, a major locus was identified on chromosome 18 with a lod score of 15. This was responsible for an 8- to 10-fold increase in tumor multiplicity in males and females, respectively, having the AA and CC genotypes at the D18Mit188 marker locus. It mapped close to Dcc (deleted in colorectal cancer). A locus on chromosome 4 (lod score 6.5) had the resistant allele in strain A/J and the susceptible allel e in BALB/c, with a 14-fold difference in tumor multiplicity between m ice of the AA and CC: genotypes. This mapped close to the Cdkn2a (cycl in-dependent kinase inhibitor 2A) locus, which is commonly deleted in mouse lung tumors. Two loci with smaller effects (lod scores 3.03 and 3.25) were identified on chromosomes 1 and 11. There was also signific ant sexual dimorphism in tumor multiplicity both among 151 F-2 hybrids and among 52 mice resulting from a backcross to strain A/J, with male s having higher tumor counts than females. (C) 1998 Academic Press.