Genetic heterogeneity of inflammatory response and skin tumorigenesis in phenotypically selected mouse lines

ABSTRACT

Non-inbred AIR (AIRmax, AIRmin) and Car (Car-S, Car-R) mouse lines were generated from the same eight inbred mice through bidirectional selective breeding for acute inflammatory response and for susceptibility to two-stage skin tumorigenesis, respectively. Because AIR lines also showed a differential predisposition to skin tumorigenesis and Car lines differed in the extent of inflammatory response, we carried out genome-wide association studies using SNP arrays to identify the genetic elements affecting skin tumor susceptibility and inflammatory response in AIR and Car lines. We found that the phenotypic outcome reflects a specific genetic profile in each mouse line, suggesting that distinct genetic elements, selected by differential genetic drifts, and exerting pleiotropic effects in each mouse population, control the skin tumor susceptibility and inflammatory response phenotypes. These findings point to the complex link between skin tumor susceptibility and inflammatory response in mice