Experiment
BALB/c and CBA/Ca inbreds, and their F1 and backcross progeny were informative in mapping alpha particle induced osteosarcoma in mice. 169 (BALB/c x (BALB/c x CBA/Ca) backcross progeny and 53 polymorphic markers spaced, on average, 18 cM apart were used in QTL mapping. Parental strain BALB/c exhibits increased osteosarcoma incidence and decreased mean latency time compared to parental strain CBA/Ca.
Ossc2, a locus identified in this study was previously mapped to mouse Chromosome 14 in Rosemann M et al., "Bone tumorigenesis inducedby alpha-particle radiation: mapping of genetic Loci influencing predisposition in mice." Radiat Res 2002 Apr;157(4):426-34. Only the Ossc2 locus was significant, LOD=3.31, peaking at marker D14Mit125. The 95% confidence interval of Ossc2 spans 2.9 cM - 33.7 cM.
07.22.2015 Curator Note: Because Ossc2 was orginally mapped in the publication noted above using a T Stock x (C3H/HeJ x 102/El)F1 population, which differs from the cross used here, we consider the current map study a separate mapping experiment and have named this QTL Ossc3.
Four additional suggestive loci were mapped: one to Chr 4 with a peak at D4Mit172; another mapped to Chr 5 with a peak at D5Mit24, another mapped to Chr 12 with a peak at D12Mit157, and another to Chr 18 peaking at D18Mit119. Thesuggestive loci all added to increased tumor susceptibility and modified the effect to Ossc3.
Heterozygosity for BALB/c- and CBA/Ca-derived alleles at Ossc3 (chr14) and D18Mit119 (chr18) confer increased susceptibility to alpha particle induced osteocarsoma.
Homozygosity for BALB/c-derived alleles at D4Mit172 (chr4), D5Mit24 (chr5), and D12Mit157 (chr12) enhanced susceptibility to alpha particle induced osteosarcoma.
Backcross animals inheriting susceptibility alleles at all 5 mapped loci exhibit the highest osteosarcoma incidence and the shortest latency time.
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