International Mammalian Genome Society

The 14th International Mouse Genome Conference (2000)

Table of Contents * Genes, Physical Mapping and Sequencing * Gene Identification * Bioinformatics * Common Resources * RIKEN Session * Functional Genomics * Complex Traits * Mutagenesis * Developmental Genetics and Differentiation * Verne Chapman Memorial Lecture I and II

Susceptibilities to g-ray Radiation-induced Thymic Lymphoma in Congenic Strains

Y. Saito1, Y. Ochiai¹, Y. Kodama¹, Y. Tamura¹, T. Togashi¹, H. Sato¹, H. Okano¹, T. Miyazawa¹, S. Wakana², O. Niwa³, and R. Kominami^1
1Department of Biochemistry, Niigata University School of Medicine, Asahimachi 1-757, Niigata 951-8122,
²The Institute of Physical and Chemical Research Genome Science Center,
³Radiation Biology Center, Kyoto University, Japan

BALB/c is a susceptible strain for the development of g-ray radiation-induced thymic lymphoma whereas MSM shows resistance. This indicates effects of different genetic backgrounds on lymphomagenesis. In order to localize susceptibility loci responsible for the background effects, the two types of backcross mice, N2M mice (backcrossed to MSM) and N2C mice (backcrossed to BALB/c), were produced and subjected to g-ray irradiation. N2C backcross mice exhibited lymphoma incidences of 70% (51/73), which was similar to that of BALB/c and F1 mice; in contrast, only 27% (59/220) of N2M mice developed lymphoma. Association studies revealed three susceptivility loci and one resistance locus: D2Mit15 (c²= 8.5), D4Mit12 (c²= 8.1), D5Mit101 (c²= 7.0) and D5Mit5 (c²= 7.2). Co-operative effect of these loci was also suggested; for instance, N2M mice with BALB/c-derived alleles both at D2Mit15 and D4Mit12 show a higher incidence and a shorter latency than mice with MSM alleles (c²= 15.0). Congenic strains for each locus have been produced using a marker-assisted breeding strategy and employed for susceptibility assay to obtain independent evidence for linkage to the BALB/c or MSM chromosomes. One susceptibility locus at D4Mit12 has been confirmed using 73 mice for the assay (c²= 15.0). These studies will provide clues to susceptibility loci responsible for g -ray radiation-induced thymic lymphoma.