Validation of the Mouse Targeted tk+/- In Vivo System for Use in Mutagenicity Studies

1. To expand a colony of transgenic Tk+/- mice using breeding of tk+/- founders and C57Bl/6 mice, and to transfer the Tk+/- genotype to a C57Bl/6 background; 2. To determine spontaneous mutant frequencies at the Tk and Hprt loci of splenic T-lymphocytes for mice of different ages; 3. To induce mutations in Tk+/- transgenic mice using treatment with the point mutagen ENU and the clastogens BLM and y-radiation, and to measure the kinetics of mutant induction at the Tk and Hprt loci; 4. To breed transgenic Tk+/- parents in an attempt to derive Tk-/- knockout mice, and study the biological signifcance of the Tk gene in mice; 5. To determine how the Tk-/- genotype may effect mutant frequencies at the Hprt locus.