Identifying genetic factors determining acute inflammatory reactivity and predisposition to carcinogenesis through a phenotypically selected mouse strains model

Abstract

Two non isogenic mouse lines selected according to the maximal (AIRmax) or minimum (AIRmin) acute inflammatory response presented different resistance to lung and skin chemical carcinogenesis. AIRmax mice are resistant whereas the AIRmin mice are susceptible, and there are many indications in these strains of shared genetic regulation between acute inflammatory reactivity and chemical carcinogenesis predisposition phenotypes. Our purpose consists to detect genes that regulate the acute inflammatory response variations in these strains and the possible involvement of these genes in neoplasic processes. To identify these genes we will carry out the whole genome scans of these animals for mapping candidate chromosomal regions, employing a large microsatellites and SNPs (single nucleotide polymorphisms) markers panel in co-segration studies. For this, we will use new genotyping technologies using DNA pools in microarrays that allow parallel analysis of thousands of SNPs in a large number of individuals (SNP-MaP “SNP Microarray and Pooling”) in an extremely fast, and more accurate way compared to traditional methodologies. These automated technologies will be used under supervision of Dr. Tommaso Dragani head of Polygenic Inheritance Unit at the Istituto Nazionale Tumori of Milan, which has a collaborative work with us. The functional characterization of localized candidate genes will be carried out latter by in vitro assays.