Fig.1. Schematic illustration of MutaTM mouse. NHEJ plays a major role in radiation-mutagenesis in mouse tissues

Radiation induces many kinds of DNA damage. The damage is repaired by different types of DNA repair systems. Occasionaly, however, alteration of DNA information (mutation) takes place because of errors in the repair process. The mutation is also induced when DNA is replicated on the damage before it is repaired. In a long period of life, the mutation contributes to the induction of cancer and probably to life shortening. Although this scenario is widely accepted, the details of the process are not understood well, especially at tissue level. Here we asked how important the NHEJ (non-homologous end-joining) system is in the production of radiation-induced mutation in different tissues of mice. NHEJ is one of the two major repair pathways to rejoin DNA double strand breaks. We crossed Ku70(+/-) mice [1] with MutaTM mice harboring lacZ gene wrapped-up in lambda phage genome [2]. The Ku70 protein plays a key role in NHEJ process. The lacZ gene can monitor all kinds of mutations except a large deletion of more than a few kbp. The crossing was continued for 2 generations to obtain Ku70(+/+)·lacZ(+), Ku70(+/-)·lacZ(+) and Ku70(-/-)·lacZ(+) mice. Irradiation of the mice with 20 Gy o