International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany


POSTER 114 - THE MUS SPRETUS VARIANT FOR PRKDC GENE, A FULLY DOMINANT ALLELE INVOLVED IN THE GENETIC DETERMINISM OF RESISTANCE TO GAMMA-RADIATION-INDUCED THYMIC LYMPHOMAS

Santos J
Dpto. Biología. Lab. Genética Molecular Humana. Fac. Ciencias. Universidad Autónoma de Madrid. 28049-Madrid. Spain. Phone 34-91-3978200. FAX 34-91-3978202.

Co-Authors: 1) López P, 1) Vaquero C, 1) Matabuena M, 1) Villa M, 1) Fernández P, 2) Montagutelli X, 2) Szatanik M, 2) Gué net JL and 1) Fernández-Piqueras J.
Institutions: 1) Dpto. Biología. Lab. Genética Molecular Humana. Fac. Ciencias. Universidad Autónoma de Madrid. 28049-Madrid. Spain. Phone 34-91-3978200. FAX 34-91-3978202. 2) Unité de Génétique des Mammifères. Institut Pasteur, 75724-Paris, France

Interspecific Consomic strains (ICS) and Interspecific Recombinant Congenic strains (IRCS) represent a valuable addition to existing tools for the genetics analysis of cancer predisposition. Working on gamma-radiation-induced thymic lymphoma (RITL) susceptibility with ICS that carry Mus spretus chromosomes derived from the wild inbred strain STF/Pas on a C57BL/6 background, we have previously located a thymic lymphoma resistance locus (Tlyr1) on mouse chromosome 19 (Santos et al., 2002, Oncogene, 21, 6680-6683). In this work, an extension of our initial genome screening of RITL susceptibility on ICS has provided evidence for another resistance locus on mouse chromosome 16 located close to the marker D16Mit34, we named as Tlyr2. In this study, the Prkdc gene, which encodes the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs), was examined as a potential candidate for the Tlyr2 locus. Naturally occurring functional allelic variants of Prkdc have been associated with inherited predisposition to radiation-induced tumours among mouse strains with BALB/c being susceptible and C57BL/6 being resistant. Here, we provide evidence that the DNA-PKcs protein expression in mice carrying the STF/Pas (Mus spretus) Prkdc allele is increased as compared with C57BL/6, suggesting that the elevated resistance to RITL development in irradiated mice consomics for a segment of Mus spretus chromosome 16 might be attributed to a new functional polymorphism of this gene.


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