First Author | Barber RC | Year | 2004 |
Journal | Mutat Res | Volume | 554 |
Issue | 1-2 | Pages | 287-95 |
PubMed ID | 15450426 | Mgi Jnum | J:93788 |
Mgi Id | MGI:3505684 | Doi | 10.1016/j.mrfmmm.2004.05.003 |
Citation | Barber RC, et al. (2004) Germline mutation rates at tandem repeat loci in DNA-repair deficient mice. Mutat Res 554(1-2):287-95 |
abstractText | Mutation rates at two expanded simple tandem repeat (ESTR) loci were studied in the germline of non-exposed and irradiated severe combined immunodeficient (scid) and poly(ADP-ribose) polymerase (PARP-1-/-) deficient male mice. Non-exposed scid and PARP-/- male mice showed considerably elevated ESTR mutation rates, far higher than those in wild-type isogenic mice and other inbred strains. The irradiated scid and PARP-1-/- male mice did not show any detectable increases in their mutation rate, whereas significant ESTR mutation induction was observed in the irradiated wild-type isogenic males. ESTR mutation spectra in the scid and PARP-1-/- strains did not differ from those in the isogenic wild-type strains. Considering these data and the results of previous studies, we propose that a delay in repair of DNA damage in scid and PARP-1-/- mice could result in replication fork pausing which, in turn, may affect ESTR mutation rate in the non-irradiated males. The lack of mutation induction in irradiated scid and PARP-1-/- can be explained by the high cell killing effects of irradiation on the germline of deficient mice. |