Analysis of ENU-induced mutations exhibiting an elevated acoustic startle response.

Trp53 is one of the best characterized tumor suppressor genes. Thymic lymphoma (TL)is the main malignancy developed in p53 Knock Out mice, which shortens their lifespan to an average 5 months. Mouse consomic(chromosome substitution) strains are useful for dissecting the effect of genetic background on the phenotype of hereditary malignancies. We sought to map some of such gene modifiers for p53-related TLs using consomic strains in which one C57BL/6J (B6) chromosome was replaced by its M.spretus homologue. We herein report the results with the first consomic line generated: B6 mice carrying M.spretus chromosome 19 (B6-sp19). We crossed the p53 deletion (B6 background, from T.Jacks) into B6-sp19 and followed the lifespan of p53-/- mice homozygous or heterozygous for various portions of M.spretus chromosome 19. Among 49 p53-/- mice that developed thymic lymphoma, the survival rate was significantly longer in animals heterozygous for the portion of M.spretus including D19mit20 (Wilcoxon Test, p= 0.05 vs B6; p< 0.05 vs B6-sp 19). This portion of chr.19 must contain gene(s) that reduce the age-dependent penetrance of the p53 -/- TL only when heterozygous. Thus, we are focussing first on candidate genes coding for molecules known to function as multimers, in which the presence of one M.spretus-derived subunit might affect the function of the whole molecule most significantly.