1. ¹Department of Genetics, University of Leicester, Leicester, UK
2. ²Department of Obstetrics and Gynaecology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

Correspondence: Professor YE Dubrova, Department of Genetics, University of Leicester, University Road, Leicester LE1 7RH, UK. E-mail: yed2@le.ac.uk

³These two authors contributed equally to this work.

Received 2 October 2006; Revised 23 November 2006; Accepted 1 December 2006; Published online 29 January 2007.

Abstract

The results of a number of recent studies show that mutation rates in the offspring of irradiated parents are substantially elevated, however, the effect of parental genotype on transgenerational instability remains poorly understood. Here, we have analysed the mutation frequency at an expanded simple tandem repeat (ESTR) locus in the germline and bone marrow of the first-generation male offspring of control and irradiated male mice. The frequency of ESTR mutation was studied in the offspring of two reciprocal matings scid BALB/c and BALB/c scid, which were compared with that in BALB/c mice. In the offspring of the BALB/c BALB/c and scid BALB/c matings, which were conceived after paternal sperm irradiation, the frequency of ESTR mutation was significantly elevated in both tissues. In contrast, ESTR mutation frequency was only slightly elevated in the offspring of BALB/c scid mating conceived after paternal irradiation. The results of this study suggest that the oocytes of scid females are unable to fully support the repair of double-strand breaks induced in paternal sperm which may in turn result in the elimination of cells/embryos containing high levels of DNA damage, thus partially preventing the manifestation of genomic instability.