Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Short Communication
  • Published:

Maternal effects of the scid mutation on radiation-induced transgenerational instability in mice

Oncogene volume 26, pages 4720–4724 (2007)Cite this article

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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  • Ahmadi A, Ng S-C . (1999). Fertilizing ability of DNA-damaged spermatozoa. J Exp Zool 284: 696–704.

    Article  CAS  PubMed  Google Scholar 

  • Allen C, Kurimasa A, Brenneman MA, Chen DJ, Nickoloff JA . (2002). DNA-dependent protein kinase suppresses double-strand break-induced and spontaneous homologous recombination. Proc Natl Acad Sci USA 99: 3758–3763.

    Article  CAS  PubMed  Google Scholar 

  • Barber R, Plumb MA, Boulton E, Roux I, Dubrova YE . (2002). Elevated mutation rates in the germline of first- and second-generation offspring of irradiated male mice. Proc Natl Acad Sci USA 99: 6877–6882.

    Article  CAS  PubMed  Google Scholar 

  • Barber RC, Hickenbotham P, Hatch T, Kelly D, Topchiy N, Almeida G et al. (2006). Radiation-induced transgenerational alterations in genome stability and DNA damage. Oncogene 25: 7336–7342.

    Article  CAS  PubMed  Google Scholar 

  • Barber RC, Miccoli L, van Buul PPW, Burr KL-A, van Duyn-Goedhart A, Angulo JF et al. (2004). Germline mutation rates at tandem repeat loci in DNA-repair deficient mice. Mutat Res 554: 287–295.

    Article  CAS  PubMed  Google Scholar 

  • Barton TS, Robaire B, Hales BF . (2005). Epigenetic programming in the preimplantation rat embryo is disrupted by chronic paternal cyclophosphamide exposure. Proc Natl Acad Sci USA 102: 7865–7870.

    Article  CAS  PubMed  Google Scholar 

  • Biedermann KA, Sun JR, Giaccia AJ, Tosto LM, Brown JM . (1991). scid mutation in mice confers hypersensitivity to ionizing radiation and a deficiency in DNA double-strand break repair. Proc Nat Acad Sci USA 88: 1394–1397.

    Article  CAS  PubMed  Google Scholar 

  • Blunt T, Gell D, Fox M, Taccioli GE, Lehmann AR, Jackson SP et al. (1996). Identification of a nonsense mutation in the carboxyl-terminal region of DNA-dependent protein kinase catalytic subunit in the scid mouse. Proc Natl Acad Sci USA 93: 10285–10290.

    Article  CAS  PubMed  Google Scholar 

  • Derijck AAHA, van der Heijden GW, Giele M, Philippens MEP, van Bavel CCAW, de Boer P . (2006). H2AX signalling during sperm chromatin remodelling in the mouse zygote. DNA Repair 5: 959–971.

    Article  CAS  PubMed  Google Scholar 

  • Dubrova YE, Plumb M, Brown J, Fennelly J, Bois P, Goodhead D et al. (1998). Stage specificity, dose response, and doubling dose for mouse minisatellite germ-line mutation induced by acute radiation. Proc Natl Acad Sci USA 95: 6251–6255.

    Article  CAS  PubMed  Google Scholar 

  • Dubrova YE, Plumb M, Gutierrez B, Boulton E, Jeffreys AJ . (2000). Transgenerational mutation by radiation. Nature 405: 37.

    Article  CAS  PubMed  Google Scholar 

  • Festing M . (1996). Origin and characteristics of Inbred strains of mice. In: Lyon MF, Rastan S, Brown SDM (eds). Genetic Variants and Strains of the Laboratory Mouse, Vol. 2. Oxford University Press: Oxford, pp 1537–1576.

    Google Scholar 

  • Fiorenza MT, Bevilacqua A, Bevilacqua S, Mangia F . (2001). Growing dictyate oocytes, but not early preimplantation embryos, of the mouse display high levels of DNA homologous recombination by single-strand annealing and lack DNA nonhomologous end joining. Dev Biol 233: 214–224.

    Article  CAS  PubMed  Google Scholar 

  • Generoso WM, Cain KT, Krishna M, Huff SW . (1979). Genetic lesions induced by chemicals in spermatozoa and spermatids of mice are repaired in the egg. Proc Natl Acad Sci USA 76: 435–437.

    Article  CAS  PubMed  Google Scholar 

  • Harrouk W, Codrington A, Vinson R, Robaire B, Hales BF . (2000). Paternal exposure to cyclophosphamide induces DNA damage and alters the expression of DNA repair genes in the rat preimplantation embryo. Mutat Res 461: 229–241.

    Article  CAS  PubMed  Google Scholar 

  • Jimenez GS, Bryntesson F, Torres-Arzayus MI, Priestley A, Beeche M, Saito S et al. (1999). DNA-dependent protein kinase is not required for the p53-dependent response to DNA damage. Nature 400: 81–83.

    Article  CAS  PubMed  Google Scholar 

  • Marchetti F, Wyrobek AJ . (2005). Mechanisms and consequences of paternally-transmitted chromosomal abnormalities. Birth Defects Res C 75: 112–129.

    Article  CAS  Google Scholar 

  • Matsuda Y, Tobari I . (1989). Repair capacity of fertilized mouse eggs for X-ray damage induced in sperm and mature oocytes. Mutat Res 210: 35–47.

    Article  CAS  PubMed  Google Scholar 

  • Mohrenweiser HW, Wilson DM, Jones IM . (2003). Challenges and complexities in estimating both the functional impact and the disease risk associated with the extensive genetic variation in human DNA repair genes. Mutat Res 526: 93–125.

    Article  CAS  PubMed  Google Scholar 

  • Okayasu R, Suetomi K, Yu Y, Silver A, Bedford JS, Cox R et al. (2000). A deficiency in DNA repair and DNA-PKcs expression in the radiosensitive BALB/c mouse. Cancer Res 60: 4342–4345.

    CAS  PubMed  Google Scholar 

  • Olsen K-A, Lindeman B, Wiger R, Duale N, Brunborg G . (2005). How do male germ cells handle DNA damage? Toxicol Appl Pharmacol 207: S521–S531.

    Article  CAS  Google Scholar 

  • Rassoulzadegan M, Grandjean V, Gounon P, Vincent S, Gillot I, Cuzin F . (2006). RNA-mediated non-mendelian inheritance of an epigenetic change in the mouse. Nature 241: 469–474.

    Article  Google Scholar 

  • Rothkamm K, Kruger I, Thompson LH, Lobrich M . (2003). Pathways of DNA double-strand break repair during the mammalian cell cycle. Mol Cell Biol 23: 5706–5715.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rousseaux S, Caron C, Govin J, Lestrat C, Faure AK, Khochbin S . (2005). Establishment of male-specific epigenetic information. Gene 345: 139–153.

    Article  CAS  PubMed  Google Scholar 

  • Searle AG . (1974). Mutation induction in mice. Adv Radiat Biol 4: 131–207.

    Article  Google Scholar 

  • Shimura T, Inoue M, Taga M, Shiraishi K, Uematsu N, Takei N et al. (2002). p53-dependent S-phase damage checkpoint and pronuclear cross talk in mouse zygotes with X-irradiated sperm. Mol Cell Biol 22: 2220–2228.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wallace M, Coates PJ, Wright EG, Ball KL . (2001). Differential post-translational modification of the tumour suppressor proteins Rb and p53 modulate the rates of radiation-induced apoptosis in vivo. Oncogene 20: 3597–3608.

    Article  CAS  PubMed  Google Scholar 

  • Yauk CL, Dubrova YE, Grant GR, Jeffreys AJ . (2002). A novel single molecule analysis of spontaneous and radiation-induced mutation at a mouse tandem repeat locus. Mutat Res 500: 147–156.

    Article  CAS  PubMed  Google Scholar 

  • Yu Y, Okayashi R, Weil MM, Silver A, McCarthy M, Zabriskie R et al. (2001). Elevated breast cancer risk in irradiated BALB/c mice associates with unique functional polymorphism of the Prkdc (DNA-dependent protein kinase catalytic subunit) gene. Cancer Res 61: 1820–1824.

    CAS  PubMed  Google Scholar 

  • Zeng F, Baldwin DA, Schultz RM . (2004). Transcript profiling during preimplantation mouse development. Dev Biol 272: 483–496.

    Article  CAS  PubMed  Google Scholar 

  • Zhang S, Ramsay ES, Mock BA . (1998). Cdkn2a, the cyclin-dependent kinase inhibitor encoding p16INK4a and p19ARF, is a candidate for the plasmacytoma susceptibility locus, Pctr1. Proc Natl Acad Sci USA 95: 2429–2434.

    Article  CAS  PubMed  Google Scholar 

  • Zheng N, Monckton DG, Wilson G, Hagemeister F, Chakraborty R, Connor TH et al. (2000). Frequency of minisatellite repeat number changes at the MS205 locus in human sperm before and after cancer chemotherapy. Environ Mol Mutagen 36: 134–145.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Bianca Lemmers and Iris Lamers of the Central Animal Facility of Radboud University for expert animal care. This work was supported by a grant from the European Commission (YED and PDB). YED work was also supported in part by grants from the Wellcome Trust, the Department of Energy and the Medical Research Council.

Author information

Author notes

  1. T Hatch and A A H A Derijck: These two authors contributed equally to this work.

Authors and Affiliations

  1. Department of Genetics, University of Leicester, Leicester, UK

    T Hatch, P D Black & Y E Dubrova

  2. Department of Obstetrics and Gynaecology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

    A A H A Derijck, G W van der Heijden & P de Boer

Authors
  1. T Hatch
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A A H A Derijck
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P D Black
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. G W van der Heijden
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. P de Boer
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Y E Dubrova
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Y E Dubrova.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hatch, T., Derijck, A., Black, P. et al. Maternal effects of the scid mutation on radiation-induced transgenerational instability in mice. Oncogene 26, 4720–4724 (2007). https://doi.org/10.1038/sj.onc.1210253

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1210253

Keywords

Search

Advanced search

Quick links