? To construct a new and more powerful mouse model, based on the generation of interspecific consomic and recombinant congenic mice, for the detection of new cancer predisposing genes.
? To identify genes that confer resistance to thymic lymphomas induced by -irradiation on Mus spretus chromosomes.
? To characterise candidate genes for the pulmonary resistance 1 locus on Mus spretus chromosome 1 1.
The goal of this investigation is the identification and characterization of genetic factors that confer resistance to carcinogen-induced tumorigenesis in mice. We will develop a original and more powerful mouse model for the detection of new cancer predisposition genetic factors. This experimental, system is based on the induction of tumors in interspecific consomic and recombinant congenic mice, derived from parental strains of differing tumor susceptibility. In particular, we will use the tumor-sensitive laboratory strain C57BL/6J and the tumor-resistant strain of wild origin Mus spretus to generate consomic and congenic individuals. Two types of carcinogen-induced tumors will be analysed in this project: thyrnic lymphomas induced bygamma-irradiation and lung tumors induced by urethane treatment. To locategenes controlling the thyrnic lymphoma resistant phenotype, we will analyse the incidence of thymic lymphomas in individuals belonging to different interspecific consomic strains. Subsequently, a precise location of these genetic factors will be undertaken by using series of interspecific recombinant congenic strains derived from resistant-consomic mouse lines. The study of the genetic predisposition to lung tumorigenesis will focus on the isolation of Mus spretus derived gene/s for the pulmonary resistance 1(Par 1) locus on chromosome 11 by mRNA differential display technique. The use of consomic mice with Mus spretus derived chromosomes will also be used for a faster mapping of differentially expressed genes isolated by the mRNA differential display technique. Every differentially expressed such genes that will map to the region where a cancer resistance locus has been detected, will be tentatively cloned and characterized in the tumor susceptible strain and the resistant mouse species Mus spretus.
Keywords: Genetic predisposition to cancer, thymic lymphomas, gamma-irradiation, lung tumors, urethane treatment, consomic and congenic mice, cancer resistance genes.
Funding SchemeCSC - Cost-sharing contracts
38071 La Laguna