RESUMEN
AIRmax and AIRmin mouse lines show a differential lung inflammatory response and differential lung tumor susceptibility after urethane treatment. The transcript profile of approximately 24,000 known genes was analyzed in normal lung tissue of untreated and urethane-treated AIRmax and AIRmin mice. In lungs of untreated mice, inflammation-associated genes involved in pathways such as "leukocyte transendothelial migration", "cell adhesion" and "tight junctions" were differentially expressed. Moreover, gene expression levels differed significantly in urethane-treated mice; in AIRmin mice, modulation of expression of genes involved in pathways associated with inflammatory response paralleled the previously observed persistent infiltration of inflammatory cells in the lung of these mice.
Asunto(s)
Transformación Celular Neoplásica/genética , Neoplasias Pulmonares/genética , Pulmón/fisiología , Neumonía/genética , Animales , Transformación Celular Neoplásica/inducido químicamente , Transformación Celular Neoplásica/patología , Modelos Animales de Enfermedad , Femenino , Expresión Génica/efectos de los fármacos , Perfilación de la Expresión Génica , Predisposición Genética a la Enfermedad , Humanos , Pulmón/efectos de los fármacos , Pulmón/patología , Neoplasias Pulmonares/inducido químicamente , Neoplasias Pulmonares/patología , Masculino , Ratones , Neumonía/inducido químicamente , Neumonía/patología , UretanoRESUMEN
AIRmax and AIRmin mouse lines show a differential lung inflammatory response and differential lung tumor susceptibility after urethane treatment. The transcript profile of 24,000 known genes was analyzed in normal lung tissue of untreated and urethane-treatedAIRmax and AIRmin mice. In lungs of untreated mice, inflammation-associated genes involved in pathways such as leukocyte transendothelial migration, cell adhesion and tight junctions were differentially expressed. Moreover, gene expression levels differed significantly in urethane-treated mice; in AIRmin mice, modulation of expression of genes involved in pathways associated with inflammatory response paralleled the previously observed persistent infiltration of inflammatory cells in the lung of these mice.
Asunto(s)
Animales , Ratas , Neoplasias Pulmonares , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/inmunología , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Relación Dosis-Respuesta InmunológicaRESUMEN
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