At least four 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 susceptibility to the induction of lung adenomas by urethane in an F2 cross between A/J and BALB/cOlaHsd have been mapped. Following microsatellite typing of mice with resistant and susceptible phenotypes at 97 microsatellite 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 allele in BALB/c, with a 14-fold difference in tumor multiplicity between mice of the AA and CC genotypes. This mapped close to the Cdkn2a (cyclin-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 significant sexual dimorphism in tumor multiplicity both among 151 F2 hybrids and among 52 mice resulting from a backcross to strain A/J, with males having higher tumor counts than females.
Festing
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MRC Toxicology Unit, Hodgkin Building, University of Leicester, Lancaster Road, Leicester, LE1 9HN, United Kingdom. mfwf1@leicester.ac.uk
Lin
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Devereux
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Gao
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Yang
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Anna
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White
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Malkinson
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You
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D000236:Adenoma / Q000139:chemically induced / Q000235:genetics*; D000818:Animals; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D005260:Female; D020022:Genetic Predisposition to Disease; D008126:Lod Score; D008175:Lung Neoplasms / Q000139:chemically induced / Q000235:genetics*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains / Q000235:genetics*; D018895:Microsatellite Repeats; D019655:Quantitative Trait, Heritable; D012737:Sex Factors; D014520:Urethane / Q000633:toxicity
D014520:Urethane