Effects of the mutation on X-ray-induced deletions in the brain and spleen of delta mice.

BACKGROUND

DNA-dependent protein kinase (DNA-PK), consisting of a Ku heterodimer (Ku70/80) and a large catalytic subunit (DNA-PKcs), plays an important role in the repair of DNA double-strand breaks via non-homologous end-joining (NHEJ) in mammalian cells. Severe combined immunodeficient () mice carry a mutation in the gene encoding DNA-PKcs and are sensitive to ionizing radiation. To examine the roles of DNA-PKcs in the generation of deletion mutations in vivo, we crossed mice with delta transgenic mice for detecting mutations.

RESULTS

The and wild-type (WT) delta transgenic mice were irradiated with a single X-ray dose of 10 Gy, and Spi mutant frequencies (MFs) were determined in the brain and spleen 2 days after irradiation. Irradiation with X-rays significantly enhanced Spi MF in both organs in the and WT mice. The MFs in the brain of irradiated mice were significantly lower than those in WT mice, i.e., 2.9 ± 1.0 × 10 versus 5.0 ± 1.1 × 10 ( < 0.001), respectively. In the spleen, however, both mouse strains exhibited similar MFs, i.e., 4.1 ± 1.8 × 10 versus 4.8 ± 1.4 × 10. Unirradiated and WT mice did not exhibit significant differences in MFs in either organ.

CONCLUSIONS

DNA-PKcs is unessential for the induction of deletion mutations in the spleen, while it plays a role in this in the brain. Therefore, the contribution of DNA-PKcs to NHEJ may be organ-specific.