Identification of genetic factors determinant of acute inflammatory reactivity and carcinogenesis predisposition employing a model of fenotipically selected mouse strains

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 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. The functional characterization of localized candidate genes will be carried out latter by in vitro assays. These methodologies and 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. (AU)