SPONTANEOUS AND X-RAY-INDUCED DELETION MUTATIONS IN A LACZ PLASMID-BASED TRANSGENIC MOUSE MODEL

Transgenic mouse mutation models carrying bacterial marker genes in bacteriophage lambda shuttle vectors have been applied to study spontaneous or induced mutations in vivo. However, due to the nature of the shuttle vector these models are insensitive to large deletions. Clastogenic agents, which predominantly induce large deletions, were therefore found to yield very low responses in these assays. Here we report the use of LacZ plasmid-based transgenic mice, allowing the detection of a broad spectrum of mutations. Treatment of mice with X-rays (5 X 50 rads) resulted in induction of up to about 5-fold higher mutation frequencies in lung, spleen and liver. Analysis of spontaneous and induced mutant LacZ genes indicated that at least 40-50% of all mutations were caused by deletions. The possibility of detecting a broad spectrum of mutations with this system suggests that the LacZ plasmid-based transgenic mouse may be the mammalian model of choice for studying spontaneous and induced mutations in vivo.