Artículo
en Inglés
| SES-SP, SESSP-IBPROD, SES-SP | ID: but-ib17772
The SM /J mousestrain is resistant to chemically-induced lungtumorigenesis despite having a haplotype, in the pulmonary adenoma susceptibility locus (Pas1 ) locus, that confers tumor susceptibility in other strains. To clarify this inconsistent genotype-phenotype correlation, we crossed SM /J mice with another resistant strain and conducted genome-wide linkage analysis in the (C57BL /6J × SM /J)F2 progeny exposed to urethane to induce lungtumors. Overall, >80% of F2 mice of both sexes developed from 1 to 20 lungtumors. Genotyping of 372 F2 mice for 744 informative non-redundant SNPs dispersed over all autosomal chromosomes revealed four quantitative trait loci (QTLs ) affecting lungtumor multiplicity, on chromosomes 3 (near rs13477379), 15 (rs6285067), 17 (rs33373629) and 18 (rs3706601), all with logarithm of the odds (LOD ) scores >5. Four QTLs modulated total lungtumor volume, on chromosome 3 (rs13477379), 10 (rs13480702), 15 (rs6285067) and 17 (rs3682923), all with LOD scores >4. No QTL modulating lungtumor multiplicity or total volume was detected in Pas1 on chromosome 6. The present study demonstrates that the SM /J strain carries, at the Pas1 locus, the resistance allele a finding that will facilitate identification of the Pas1 causal element. More generally, it demonstrates that lungtumorigenesis is under complex polygenic control even in a pedigree with low susceptibility to this neoplasia, suggesting that the genetics of lungtumorigenesis is much more complex than evidenced by the pulmonary adenoma susceptibility and resistance loci that have, so far, been mapped in a small number of crosses between a few inbred strains.