International Mammalian Genome Society

The 15th International Mouse Genome Conference (2001)


POSTER 49 - INTER-SPECIFIC CONSOMIC STRAINS OF MICE PROVIDE AN EXCELLENT GENETIC TOOL IN THE SEARCHING OF g-RADIATION-INDUCED THYMIC LYMPHOMA RESISTANCE LOCI

Dr. Javier Santos
Departamento de Biología
Laboratorio Genética Molecular Humana
Facultad de Ciencias
Universidad Autónoma de Madrid
28049-Madrid
Spain

Co-Authors: 1) Santos J, 2) Montagutelli X, 3) Acevedo A, 1) Fernández M, 1) Vaquero C, 1) López P, 3) Arnau MR, 2) Szatanik M, 3) Salido E, 2) Guenet JL, 1) Fernández-Piqueras J
Institutions: 1)Departamento de Biología. Laboratorio Genética Molecular Humana. Facultad de Ciencias. Universidad Autónoma de Madrid 2)Unité de Génétique des Mammifères. Institut Pasteur 3)Departamento de Anatomía Patológica. Facultad de Medicina. Universidad de La Laguna

Based on the analysis of differences among laboratory inbred strains, several loci have already been reported as being of importance in the determinism of susceptibility to the development of spontaneous or carcinogen-induced lymphomas. However, given that most of the laboratory strains are derived from a relatively small pool of ancestors, the range of phenotypic differences analyzed remained relatively limited. The use of inbred strains established  from progenitors trapped from the wild state and their crosses with laboratory strains are efficient means to identify resistance/susceptibility genes. Using such a strategy, we demonstrated that mice derived from the Mus spretus species and their F1 hybrids with mice of the susceptible strain C57BL/6J are extremely resistant to g-radiation-induced thymic lymphoma (RITL). Analysis of the genetic determinism of this resistance with the help of inter-specific consomic strains (ICS) and inter-specific recombinant congenic strains (IRCS), allowed to identify a new thymic lymphoma resistance (Tlyr) locus mapping to the D19Mit60-D19Mit40 interval on chromosome 19. A subsequent allele loss analysis in tumors of g-treated mice from ICS and IRCS, using several markers mapped within the region defined by D19Mit60 and D19Mit40, suggested two possible locations for Tlyr, one centered at D19Mit30 and the other placed distally at D19Mit39. Further to the discovery of a new locus controlling g-radiation-induced thymic lymphomagenesis, our report emphasizes the value of ICS and IRCS for the genetic analysis of cancer predisposition.


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