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Identification of genetic factors affecting resistance and susceptibility to chemical carcinogenesis and the degree of acute inflammatory response, using a model of genetically selected mouse lines

Grant number: 03/05486-7
Support type:Research Projects - Thematic Grants
Duration: May 01, 2004 - November 30, 2008
Field of knowledge:Biological Sciences - Immunology - Immunogenetics
Principal researcher:Olga Celia Martinez Ibanez
Grantee:Olga Celia Martinez Ibanez
Home Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
Pesquisadores principais:
Marcelo de Franco

Abstract

Two non isogenic mouse lines phenotypically selected according to the maximal (AIRmax) or minimum (AIRmin) acute inflammatory response to foreign body show differential susceptibility to chemical carcinogenesis in the lungs and skin, AIRmax being resistant and AIRmin susceptible. As a consequence of the bi-directional selective process, the alleles of the genes relevant to the "maximal" and "minimum" inflammatory response phenotypes, specifically segregated in AIRmax and AIRmin lines, respectively, leading to homozygosity in AIR modifier /oci but maintaining the background genetic heterogeneity in each liDe. The analysis of the heritability of the character, during the bi-directional selective process, revealed the involvement of about 11 Quantitative Trait Loci (QTL) with additive effect, accounting for the phenotypic divergence between AIRmax and AIRmin mice. Our project aims to evaluate whether functional polymorphisms in genes which could explain the variations in the inflammatory response in the two selected mouse lines, harbor an altered risk to the development of neoplasic diseases. In order to identify these genes, two complementary strategies will be applied: 1) the search of polymorphism in candidate genes, indicated from precise phenotypes which differentiate the two lines. The differential response of AIRmax and AIRmin mice is evidenced by the number of leukocytes and the amount of proteins present in the local inflammatory exudates... (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
VORRARO, FRANCISCA; GALVAN, ANTONELLA; KOURY CABRERA, WAFA HANNA; CARNEIRO, PATRICIA SANTOS; RIBEIRO, ORLANDO GARCIA; DE FRANCO, MARCELO; STAROBINAS, NANCY; JENSEN, JOSE RICARDO; SEMAN, MICHEL; DRAGANI, TOMMASO A.; et al. Genetic Control of IL-1 beta Production and Inflammatory Response by the Mouse Irm1 Locus. JOURNAL OF IMMUNOLOGY, v. 185, n. 3, p. 1616-1621, . (03/05486-7)
GALVAN, A.; VORRARO, F.; CABRERA, W.; RIBEIRO, O. G.; STAROBINAS, N.; JENSEN, J. R.; DOS SANTOS CARNEIRO, P.; DE FRANCO, M.; GAO, X.; IBANEZ, O. C. M.; et al. Association study by genetic clustering detects multiple inflammatory response loci in non-inbred mice. Genes and Immunity, v. 12, n. 5, p. 390-394, . (03/05486-7)

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