The genome of the BALB/c mouse strain provides alleles that dominantly inhibit hepatocellular tumor development in F1 crosses with the highly hepatocarcinogenesis-susceptible C3H/He strain. Genome-wide linkage analysis using a 1536-single-nucleotide polymorphism array in a (C3H/He x BALB/c)F2 intercross population treated with urethane to induce hepatocellular tumor development revealed a locus with a major role in the resistance to hepatocarcinogenesis. This locus, designated hepatocarcinogen resistance 3 (Hpcr3) and mapping to central chromosome 15, showed a linkage at LOD score = 16.52 and accounted for 40% of the phenotypical variance. The BALB/c-derived allele at Hpcr3 reduced tumor-occupied area of the liver up to 25-fold, in a semidominant way. Additional minor loci were mapped to chromosomes 1, 10, and 18. A gene expression profile of normal adult mouse liver showed a significant association with susceptibility of BALB/c, C3H/He, and F1 mice to hepatocarcinogenesis and identified the genes expressed in the Hpcr3 locus region; moreover, this analysis implicated the E2F1 pathway in the modulation of the phenotype susceptibility to hepatocarcinogenesis. CONCLUSION: These findings, indicating the complex genetics of dominant resistance to hepatocarcinogenesis, represent a step toward the identification of the genes underlying this phenotype.

Genetic control of resistance to hepatocarcinogenesis by the mouse Hpcr3 locus / G. Manenti, A. Galvan, F.S. Falvella, R.M. Pascale, E. Spada, S. Milani, A. Gonzalez Neira, F. Feo, T.A. Dragani. - In: HEPATOLOGY. - ISSN 0270-9139. - 48:2(2008 Aug), pp. 617-623. [10.1002/hep.22374]

Genetic control of resistance to hepatocarcinogenesis by the mouse Hpcr3 locus

E. Spada;S. Milani;
2008-08

Abstract

The genome of the BALB/c mouse strain provides alleles that dominantly inhibit hepatocellular tumor development in F1 crosses with the highly hepatocarcinogenesis-susceptible C3H/He strain. Genome-wide linkage analysis using a 1536-single-nucleotide polymorphism array in a (C3H/He x BALB/c)F2 intercross population treated with urethane to induce hepatocellular tumor development revealed a locus with a major role in the resistance to hepatocarcinogenesis. This locus, designated hepatocarcinogen resistance 3 (Hpcr3) and mapping to central chromosome 15, showed a linkage at LOD score = 16.52 and accounted for 40% of the phenotypical variance. The BALB/c-derived allele at Hpcr3 reduced tumor-occupied area of the liver up to 25-fold, in a semidominant way. Additional minor loci were mapped to chromosomes 1, 10, and 18. A gene expression profile of normal adult mouse liver showed a significant association with susceptibility of BALB/c, C3H/He, and F1 mice to hepatocarcinogenesis and identified the genes expressed in the Hpcr3 locus region; moreover, this analysis implicated the E2F1 pathway in the modulation of the phenotype susceptibility to hepatocarcinogenesis. CONCLUSION: These findings, indicating the complex genetics of dominant resistance to hepatocarcinogenesis, represent a step toward the identification of the genes underlying this phenotype.
Settore MED/01 - Statistica Medica
HEPATOLOGY
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/49933
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