The Mouse Mutant “Wasted”: An Animal Model for Ataxia-Telangiectasia

  • Tadashi Inoue
  • Hideo Tezuka
  • Tsuneo Kada
  • Katsuhiro Aikawa
  • Leonard D. Shultz
Part of the Basic Life Sciences book series (BLSC, volume 39)


Ataxia-telangiectasia (AT) is a human autosomal recessive disease characterized by an increased predisposition to cancer, a progressive neurological disorder, a marked immune deficiency, and a spontaneous chromosomal instability. The frequency of AT heterozygotes in the human population has been estimated to be around 0.01. Considering that the heterozygotes are predisposed to cancer (23), it seems very important, from both a therapeutic and a preventive point of view, to elucidate the molecular mechanisms controlled by the AT gene that determine the susceptibility to cancer.


Bone Marrow Cell Chromosomal Aberration Spleen Cell Lung Fibroblast Ataxia Telangiectasia 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Agarwal, S.S., D.Q. Brown, E.J. Katz, and L.A. Loeb (1977) Screening for deficits in DNA repair by the response of irradiated human lymphocytes to phytohemagglutinin. Cancer Res. 37:3594–3598.Google Scholar
  2. 2.
    Bridges, B.A., and D.G. Harnden, eds. (1982) Ataxia-Telangiectasia, a Cellualar and Molecular Link between Cancer, Neuropathology, and Immune Deficiency, John Wiley and Sons, New York.Google Scholar
  3. 3.
    Cohen, M.M., and S.J. Simpson (1982) The effect of bleomycin on DNA synthesis in ataxia telangiectasia lymphoid cells. Environ. Mutag. 4:27–36.CrossRefGoogle Scholar
  4. 4.
    Edwards, M.J., A.M.R. Taylor, and G. Duckworth (1980) An enzyme activity in normal and ataxia-telangiectasia cell lines which is involved in the repair of gamma-irradiation induced DNA damage. Biochem. J. 188:677–682.Google Scholar
  5. 5.
    Houldsworth, J., and M.F. Lavin (1980) Effect of ionizing radiation on DNA synthesis in ataxia telangiectasia cells. Nucl. Acids Res. 8: 3709–3720.CrossRefGoogle Scholar
  6. 6.
    Inoue, T., and T. Kada (1977) Studies on DNA repair in Bacillus sub- tilis. III. Identification of an exonuclease which enhances the priming activity of y-irradiated DNA by “cleaning” damaged ends. Biochim. Biophys. Acta 478:234–243.Google Scholar
  7. 7.
    Inoue, T., K. Eirano, A. Kokoiyama, T. Kada, and H. Kato (1977) DNA repair enzymes in ataxia-telangiectasia and Bloom’s syndrome fibroblasts. Biochim. Biophys. Acta 479:497–500.Google Scholar
  8. 8.
    Inoue, T., and T. Kada (1978) Purification and properties of a Bacillus subtilis endonuclease specific for apurinic sites in DNA. J. Biol. Chem. 253:8559–8563.Google Scholar
  9. 9.
    Inoue, T., A. Yokoiyama, and T. Kada (1981) DNA repair enzyme deficiency and in vitro complementation of the enzyme activity in cell- free extracts from ataxia telangiectasia fibroblasts. Biochim. Biophys. Acta 655:49–53.Google Scholar
  10. 10.
    Inoue, T., M.S. Sasaki, A. Yokoiyama, and T. Kada (1982) Primer activating enzyme deficiency and vitro complementation of the enzyme activity in cell-free extracts from ataxia-telangiectasia fibroblasts. In Ataxia-Telangiectasia, a Cellular and Molecular Link between Cancer, Neuropathology, and Immune Deficiency, B.A. Bridges and D.G. Harnden, eds. John Wiley and Sons, New York, pp. 305–317.Google Scholar
  11. 11.
    McFarlin, D.E., W. Strober, and T.A. Waldmann (1972) Ataxia-telangiec- tasia. Medicine 51:281–314.CrossRefGoogle Scholar
  12. 12.
    Morris, C., R. Mohamed, and M.F. Lavin (1983) DNA replication and repair in ataxia telangiectasia cells exposed to bleomycin. Mutat. Res. 112:67–74.Google Scholar
  13. 13.
    Noguti, T., and T. Kada (1975) Studies on DNA repair in Bacillus subtilis. I. A cellular factor acting on y-irradiated DNA and promoting its priming activity for DNA polymerase I. Biochim. Biophys. Acta 395:284–293.Google Scholar
  14. 14.
    Noguti, T., and T. Kada (1975) Studies on DNA repair in Bacillus subtilis. II. Partial purification and mode of action of an enzyme enhancing the priming activity of y-irradiated DNA. Biochim. Biophys. Acta 395:294–305.Google Scholar
  15. 15.
    Nordeen, S.K., V.G. Schaefer, M.H. Edgell, C.A. Hutchson III, L.D. Shultz, and M. Swift (1984) Evaluation of wasted mouse fibroblasts and SV-40 transformed human fibroblasts as models of ataxia telangiectasia in vitro. Mutat. Res. 140:219–222.CrossRefGoogle Scholar
  16. 16.
    Paterson, M.C., B.P. Smith, P.H.M. Lohman, A.K. Anderson, and L. Fishman (1976) Defective excision repair of γ-ray-damaged DNA in human (ataxia telangiectasia) fibroblasts. Nature 260:444–447.CrossRefGoogle Scholar
  17. 17.
    Paterson, M.C., and P.J. Smith (1979) Ataxia-telangiectasia: An inherited human disorder involving hypersensitivity to ionizing radiation and related DNA-damaging chemicals. Ann. Rev. Genet. 13:291–318.CrossRefGoogle Scholar
  18. 18.
    Peterson, R.D.A., W.D. Kelly, and R.A. Good (1964) Ataxia-telangiec- tasia, its association with a defective th3nnus, immunological-deficiency disease, and malignancy. Lancet i:1189–1193.CrossRefGoogle Scholar
  19. 19.
    Povirk, L.F., and I.H. Goldberg (1982) Inhibition of mammalian deoxyribonucleic acid synthesis by neocarzinostatin: Selective effect on replicon initiation in CHO cells and resistant synthesis in ataxia telangiectasia fibroblasts. Biochemistry 21:5857–5862.CrossRefGoogle Scholar
  20. 20.
    Scudiero, D.A. (1980) Decreased DNA repair s3mthesis and defective colony-forming ability of ataxia telangiectasia fibroblast cell strains treated with N-methyl-N’-nitro-N-nitrosoguanidine. Cancer Res. 40:984–990.Google Scholar
  21. 21.
    Shultz, L.D., H.O. Sweet, M.T. Davisson, and D.R. Coman (1982) “Wasted,” a new mutant of the mouse with abnormalities characteristic of ataxia telangiectasia. Nature 297:402–404.CrossRefGoogle Scholar
  22. 22.
    Smith, P.J., and M.C. Paterson (1980) Gamma-ray induced inhibition of DNA synthesis in ataxia telangiectasia fibroblasts is a function of excision repair capacity. Biochem. Biophys. Res. Commun. 97:897–905.Google Scholar
  23. 23.
    Swift, M., L. Sholman, M. Perry, and C. Chase (1976) Malignant neoplasms in the families of patients with ataxia-telangiectasia. Cancer Res. 36:209–215.Google Scholar
  24. 24.
    Vincent, Jr., R.A., A.J. Fink, and P.C. Huang (1980) Unscheduled DNA synthesis in cultured ataxia telangiectasia fibroblast-like cells. Mutat. Res. 72:245–249.CrossRefGoogle Scholar
  25. 25.
    Waldmann, T.A. (1982) Immunological abnormalities in ataxia-telangiectasia. In Ataxia-Telangiectasia, a Cellular and Molecular Link between Cancer, Neuropathology, and Immune Deficiency, B.A. Bridges and D.G. Harnden, eds. John Wiley and Sons, New York, pp. 37–51.Google Scholar
  26. 26.
    de Wit, J., N.G.J. Jaspers, and D. Bootsma (1981) The rate of DNA synthesis in normal human and ataxia telangiectasia cells after exposure to X-irradiation. Mutat. Res. 80:221–226.CrossRefGoogle Scholar
  27. 27.
    Zampetti-Bosseler, F., and D. Scott (1981) Cell death, chromosome damage, and mitotic delay in human, ataxia telangiectasia and retinoblastoma fibroblasts after X-irradiation. Int. J. Radiat. Biol. 39:547–558.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Tadashi Inoue
    • 1
  • Hideo Tezuka
    • 1
  • Tsuneo Kada
    • 1
  • Katsuhiro Aikawa
    • 2
  • Leonard D. Shultz
    • 3
  1. 1.National Institute of GeneticsMishima, Shizuoka-ken 411Japan
  2. 2.Institute for Animal IndustryKukizaki, Ibaraki-ken 305Japan
  3. 3.The Jackson LaboratoryBar HarborUSA

Personalised recommendations