IDENTIFICATION OF QUANTITATIVE TRAIT LOCI CONTROLLING LEVELS OF RADIATION-INDUCED THYMOCYTE APOPTOSIS IN MICE

Thymocyte apoptosis levels are higher in C57BL/6J mice than in C3Hf/Ka m mice. Low-dose irradiation increases the numbers of thymocytes under going apoptosis, but the strain difference persists. We mapped three l oci controlling radiation-induced thymocyte apoptosis levels in F2 int ercross progeny of these strains. The strongest association of a genom ic region with an apoptosis level occurred in a region of chromosome 1 1 known to harbor a locus (or loci) important in the pathogenesis of s everal rodent models of autoimmune disease. Additional loci influencin g radiation-induced thymocyte apoptosis were identified on chromosomes 9 and 16. The genetic polymorphisms underlying these loci may have an evolutionary role in fine-tuning the apoptotic response in T cells an d may be important in the etiology of lymphoproliferative disorders an d autoimmunity. (C) 1997 Academic Press.