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The scid mutation in mice causes a general defect in DNA repair

Abstract

MICE homozygous for the scid mutation on chromosome 16 have a severe combined immune deficiency1,2 as a result of their inability to correctly rearrange their immunoglobulin and T-cell receptor genes3,4. In scid mice, when precursors for B and T lymphocytes reach the stage of development requiring expression of these surface receptors, a defective recombinase system aberrantly cuts and rejoins the receptor gene segments greatly reducing the efficiency of producing functional receptors. As a result, most scid mice have no detectable B or T lymphocytes. We have demonstrated that the scid defect is not specific to lymphocyte development. Myeloid cells and fibroblasts from scid mice show a marked increase in sensitivity to ionizing radiation, indicating that the scid mutation leads to an inability to repair DNA damage induced by ionizing radiation as well as interfering with rearrangement of the immunoglobulin and T-cell receptor genes.

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References

  1. Bosma, G. C. et al. Immunogenetics 29, 54–57 (1989).

    Article  CAS  Google Scholar 

  2. Bosma, G. C., Custer, R. P. & Bosma, M. J. Nature 301, 527–530 (1983).

    Article  ADS  CAS  Google Scholar 

  3. Malynn, B. A. et al. Cell 54, 453–460 (1988).

    Article  CAS  Google Scholar 

  4. Schuler, W. et al. Cell 46, 963–972 (1986).

    Article  CAS  Google Scholar 

  5. Till, J. E. & McCulloch, E. A. Radiat. Res. 14, 213–222 (1961).

    Article  ADS  CAS  Google Scholar 

  6. Dorshkind, K. et al. J. Immun. 132, 1804–1808 (1984).

    CAS  PubMed  Google Scholar 

  7. Till, J. E. & McCulloch, E. A. Ann. N.Y. Acad. Sci. 114, 115–125 (1964).

    Article  ADS  CAS  Google Scholar 

  8. Magli, M. C., Dick, J. E., Huszar, D., Bernstein, A. & Phillips, R. A. Proc. natn. Acad. Sci. U.S.A. 84, 789–793 (1987).

    Article  ADS  CAS  Google Scholar 

  9. Fulop, G. M. & Phillips, R. A. J. Immun. 136, 4438–4443 (1986).

    CAS  PubMed  Google Scholar 

  10. Fulop, G. M., Wu, D. D. & Phillips, R. A. in The Scid Mouse. Characterization and Potential Uses (eds Bosma, M. J., Phillips, R. A. & Schuler, W.) 171–180 (Springer, Heidelberg, 1989).

    Google Scholar 

  11. Grosschedl, R., Weaver, D., Baltimore, D. & Constantini, F. Cell 38, 647–658 (1984).

    Article  CAS  Google Scholar 

  12. Countryman, P. I. & Heddle, J. A. Mutat. Res. 41, 1343–1347 (1976).

    Article  Google Scholar 

  13. Goddard, A. D., Heddle, J. A., Gallie, B. L. & Phillips, R. A. Mutat. Res. 152, 31–38 (1985).

    Article  CAS  Google Scholar 

  14. Paterson, M. C., Bech-Hansen, N. T., Smith, P. J. & Mulvihill, J. J. in Radiation Carcinogenesis: Epidemiology and Biological Significance (eds Boice, J. D., jr & Fraumeni, J. F., jr) 319–336 (Raven, New York, 1984).

    Google Scholar 

  15. McKinnon, P. J. Mum. Genet. 75, 197–208 (1987).

    CAS  Google Scholar 

  16. Roifman, C. M. & Gelfand, E. W. in Ataxia-Telangiectasia. Genetics, Neuropathology, and Immunology of a Degenerative Disease of Childhood (eds Gatti, R. A. & Swift, M.) 273–285 (Alan R. Liss, New York, 1985).

    Google Scholar 

  17. Kim, M.-G., Schuler, W., Bosma, M. J. & Marcu, K. B. J. Immun. 141, 1341–1347 (1988).

    CAS  PubMed  Google Scholar 

  18. Tutt, M. et al. J. Immun. 138, 2338–2344 (1987).

    CAS  PubMed  Google Scholar 

  19. Arlett, C. F., Harcourt, S. A., Teo, I. A. & Broughton, B. C. in Ataxia Telangiectasia—A Cellular and Molecular Link Between Cancer, Neuropathology and Immune Deficiency (eds Bridges, B. A. & Harnden, D. G.) 347–353 (Wiley, London, 1982).

    Google Scholar 

  20. Schatz, D. G., Oettinger, M. A. & Baltimore, D. Cell 59, 1035–1048 (1989).

    Article  CAS  Google Scholar 

  21. Blackwell, T. K. & Alt, F. W. in Molecular Immunology (eds Hames, B. D. & Glover, D. M.) 1–60 (IRL, Oxford, 1988).

    Google Scholar 

  22. Cunningham, J. R., Bruce, W. R. & Webb, H. P. Phys. med. Biol. 10, 318–332 (1965).

    Article  Google Scholar 

  23. Iscove, N. N., Guilbert, L. J. & Weyman, C. Expl Cell. Res. 126, 121–126 (1980).

    Article  CAS  Google Scholar 

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Fulop, G., Phillips, R. The scid mutation in mice causes a general defect in DNA repair. Nature 347, 479–482 (1990). https://doi.org/10.1038/347479a0

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