Experiment
The pulmonary adenoma susceptibility locus, Pas15, was localized to a 0.5 Mb region on mouse Chromosome 6 using congenic lines. A 26.1 Mb region between D6Mit54 and D6Mit373 from lung tumor susceptible donor strain A/J was bred onto the susceptible C57BL/6J genetic background. Several subcongenic lines were constructed to the N9 generation and analyzed.
Pas15 was localized between D6Osu6 (145.03 Mb) and D6Osu12 (145.53 Mb). Several candidate genes mapping to this interval (Kras, Lrmp, 4930469P12Rik, Las1) were investigated. Kras mRNA expression was found to be 36% higher in A/J animals compared to C57BL/6J animals. In addition, Kras-deficient animals showed increased susceptibility to lung tumor development when administered carcinogens. Functional polymorphisms were identified between A/J and C57BL/6J sequences for Lrmp, Las1, and 4930469P12Rik.
A/J-derived alleles were found to increase lung tumor susceptibility by 8.6 fold, and also increase tumor volume by 10 fold.