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The Detection of ENU-Induced Mutants in Mice by Electrophoresis and the Problem of Evaluating the Mutation Rate Increase

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Part of the book series: Environmental Science Research ((ESRH,volume 28))

Abstract

Electrophoretic methods of mutant detection in mice are described. Spermatogonial exposure of parental male mice to a 250 mg/kg dose of ethylnitrosourea resulted in greatly elevated frequencies of electrophoretically detectable mutants in their F1 progeny. Two major categories of mutants were observed, deficiency mutants and electrophoretic mobility mutants. Deficiency mutants were induced to higher average frequencies than electrophoretic mobility mutants. Since no newly arisen mutants were found in control groups, the spontaneous background mutation rates are not known. However, various comparisons with previous data suggest that ENU caused a 1000- or greater-fold increase in the spontaneous mutation rate at some loci.

A small prenatal recessive-lethal test was also conducted, but resulting data do not substantiate the very high recessive lethal frequency that was predicted from the frequencies of extreme deficiency (null) mutatants. Recessive lethal-mutable loci may have lower spontaneous mutation rates (or be less ENU-mutagen sensitive) than some null-mutable loci. The degree to which such mutations as those detected by electrophoresis contribute measurably to harmful genetic change is difficult to assess since no obvious detrimental effects were associated with any of the induced mutants in heterozygous condition. It is possible that the combined effects of many deficiency mutations with small effects may be as significant as dominant mutations that cause severe abnormalities. However, the number of null-mutable loci of functional importance may not be large. An expanded set of loci at which biochemical genetic variation and other mutants can be detected is recommended for future investigations of induced mutation in mice.

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References

  1. R. C. Lewontin, The genetic basis of evolutionary change, Columbia University Press, New York (1974).

    Google Scholar 

  2. H. V. Mailing and L. R. Valcovic, A biochemical specific locus mutation system in mice, Arch. Toxicol., 38:45–51 (1977).

    Article  Google Scholar 

  3. E. R. Soares, TEM-induced gene mutations at enzyme loci in the mouse, Environ. Mutagenesis, 1:19–25 (1979).

    Article  MathSciNet  Google Scholar 

  4. F. M. Johnson, G. T. Roberts, R. K. Sharma, F. Chasalow, R. Zweidinger, A. Morgan, R. W. Hendren, and S. E. Lewis, The detection of mutants in mice by electrophoresis: Results of a model induction experiment with procarbazine, Genetics, 97:113–124 (1981).

    Google Scholar 

  5. F. M. Johnson and S. E. Lewis, Electrophoretically detected germinal mutations induced in the mouse by ethylnitrosourea, Proc. Natl. Acad. Sci. USA, 78:3238–3141 (1981).

    Google Scholar 

  6. W. L. Russell, E. M. Kelley, P. R. Hunsicker, J. W. Bangham, S. C. Maddux, and E. L. Phipps, Specific locus test shows ethyl nitrosourea to be the most potent mutagen in the mouse, Proc. Natl. Acad. Sci. USA, 76:5818–5819 (1979).

    Article  ADS  Google Scholar 

  7. F. M. Johnson and S. E. Lewis, The human genetic risk of airborne genotoxics: An approach based on electrophoretic techniques applied to mice, in: “Brookhaven Symposium on the Genotoxic Effects of Airborne Agents,” R. R. Tice, D. L. Costa, and K. M. Schaich, eds., pp. 595–606, Plenum Press, New York (1981).

    Google Scholar 

  8. F. M. Johnson, S. E. Lewis, L. Barnett, W. C. Worthy, and R. Batten, Problems in genetic risk assessment: The detection of transmissible point mutations in mice by electrophresis. Latin-American Course in Genetic Toxicology (1982), in press.

    Google Scholar 

  9. F. M. Johnson and S. E. Lewis, Mutation rate determinations based on electrophoretic analysis of laboratory mice, Mutation Res., 82:125–135 (1981).

    Article  Google Scholar 

  10. W. L. Russell, X-ray induced mutations in mice, Cold Spring Harbor Symp. Quant. Biol., 16:327–336 (1951).

    Google Scholar 

  11. K. G. Luning, Test of recessive lethals in the mouse, Mutation Res., 27:357–366 (1975).

    Article  Google Scholar 

  12. A.G. Searle, Mutation induction in mice, Adv. Radiation Biol., 4:131–207 (1974).

    Google Scholar 

  13. M. F. W. Festing, Inbred Strains in Biomedical Research, Oxford University Press, New York (1979).

    Google Scholar 

  14. R. A. Voelker, H. E. Schaffer, and T. Mukai, Spontaneous allozyme mutations in Drosophila melanogaster, Genetics, 94:961–968 (1980).

    Google Scholar 

  15. G. Schlager and M. M. Dickie, Spontaneous mutations and mutation rates in the house mouse, Genetics, 57:319–330 (1967).

    Google Scholar 

  16. T. C. Carter, M. F. Lyon, and R. J. S. Phillips, Genetic hazard of ionizing radiations, Nature, 182:409 (1958).

    Article  ADS  Google Scholar 

  17. M. C. Green, Mutant genes and linkage, in: “Biology of the Laboratory Mouse,” E. L. Green, ed., 2nd edition, pp. 87–150, Mraw-Hill, New York (1966).

    Google Scholar 

  18. T. Mukai, S. I. Chigusa, L. E. Mettier, and J. F. Crow, Mutation rate and dominance of genes affecting viability in Drosophila melanogaster, Genetics, 72:335–355 (1972).

    Google Scholar 

  19. J. F. Crow and R. G. Temin, Evidence for the partial dominance of recessive lethal genes in natural populations of Drosphila, Amer. Naturalist, 98:21–33 (1964).

    Article  Google Scholar 

  20. B. Wallace, Distance and the allelism of lethals in a tropical population of Drosophila melanogaster, Amer. Naturalist, 100: 565–678 (1966).

    Article  Google Scholar 

  21. B. Wallace, Mutation rates for autosomal lethals in Drosophila melanogaster, Genetics, 60:389–393 (1968).

    Google Scholar 

  22. B. Wallace, Spontaneous mutation rates for sex-linked lethals in the two sexes of Drosophila melanogaster, Genetics, 64: 553–557 (1970).

    Google Scholar 

  23. B. Wallace, E. Zouros, and C. Krimbas, Frequencies of second and third chromosome lethals in a tropical population of Drosophila melanogaster, Amer. Naturalist, 100:245–251 (1966).

    Article  Google Scholar 

  24. B. H. Judd, M. W. Shen, and T. C. Kaufman, The anatomy and function of a segment of the x-chromosome of Drosophila melanogaster, Genetics, 71:139–156 (1972)

    Google Scholar 

  25. B. Hochman, The fourth chromosome of Drosophila melanogaster, in: “The Genetics and Biology of Drosophila,” M. Ashburner and E. Novitski, eds., Vol. lb, pp. 903–925, Academic Press, London (1976).

    Google Scholar 

  26. A. Schalet, G. Lefevre, Jr., The proximal region of the x-chromosome, in: “The Genetics and Biology of Drosophila,” M. Ashburner and E. Novitski, eds., Vol. lb, pp. 848–896, Academic Press, London (1976).

    Google Scholar 

  27. S. Abrahamson, F. E. Wurgler, C. De Jongh, and H. U. Meyer, How many loci on the x-chromosome of Drosophila melanogaster can mutate to recessive lethals, Environ. Mutagenesis, 2:447–453 (1980).

    Article  Google Scholar 

  28. M. F. Lyon, Some evidence concerning the “mutational load” in inbred strains of mice, Heredity, 13:341–352 (1959).

    Article  Google Scholar 

  29. A. G. Searle, Effects of low-level irradiation on fitness and skeletal variation in an inbred mouse strain, Genetics, 50: 1159–1178 (1964).

    Google Scholar 

  30. K. G. Luning and A. G. Searle, Estimates of the genetic risks from ionizing radiation, Mutation Res., 12:291–304 (1971).

    Article  Google Scholar 

  31. K. G. Luning, Spontaneous recessive lethal mutations in the mouse, Mutation Res., 27:367–373 (1975).

    Article  Google Scholar 

  32. K. G. Luning and A. Eiche, X-ray induced recessive lethal mutations in adult and foetal female mice, Mutation Res., 92:169–180 (1982).

    Article  Google Scholar 

  33. T. C. Carter, Recessive lethal mutations induced in the mouse by chronic y-irradiation, Proc. Roy. Soc. Ser. B., 147:402–411 (1957).

    Article  ADS  Google Scholar 

  34. J. V. Neel, H. Mohrenweiser, C. Satoh, and H. B. Hamilton, A consideration of two biochemical approaches to monitoring human populations for a change in germ cell mutation rates, in: “Genetic Damage in Man Caused by Environmental Agents,” K. Berg, ed., pp. 29–47, Academic Press, New York (1979).

    Google Scholar 

  35. R. T. Greenberg and J. F. Crow, A comparison of the effect of lethal and detrimental chromosomes from Drosophila populations, Genetics, 45:1153–1168 (1960).

    Google Scholar 

  36. T. Mukai, The genetic structure of natural populations of Drosophila melanogaster, I. Spontaneous mutation rate of polygenes controlling viability, Genetics, 50:1–19 (1964).

    Google Scholar 

  37. R. T. Temin, Homozygous viability and fertility loads in Drosophila melanogaster, Genetics, 53:27–46 (1966).

    Google Scholar 

  38. U. H. Ehling, J. Favor, J. Kratochvilova, and A. Neuhauser-Klaus, Dominant cataract mutations and specific locus mutation in mice induced by radiation or ethyl nitrosourea, Mutation Res., 92:181–192 (1982).

    Article  Google Scholar 

  39. H. J. Muller, Our load of mutations, Am. J. Human Genet., 2: 111–176 (1950).

    Google Scholar 

  40. N. E. Morton, J. F. Crow, and H. J. Muller, An estimate of the mutational damage in man from data on consanguinous marriages, Proc. Natl. Acad. Sci. USA, 42:855–863 (1956).

    Article  ADS  Google Scholar 

  41. E. L. Green, Genetic effects of radiation on mammalian populations, Ann. Rev. Genet., 2:87–120 (1968).

    Article  Google Scholar 

  42. T. Ong and F. J. de Serres, Mutation induction by difunctional alkylating agents in Neurospora crassa, Genetics, 80:475–482 1975).

    Google Scholar 

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© 1983 Plenum Press, New York

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Johnson, F.M., Lewis, S.E. (1983). The Detection of ENU-Induced Mutants in Mice by Electrophoresis and the Problem of Evaluating the Mutation Rate Increase. In: de Serres, F.J., Sheridan, W. (eds) Utilization of Mammalian Specific Locus Studies in Hazard Evaluation and Estimation of Genetic Risk. Environmental Science Research, vol 28. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-3739-3_7

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  • DOI: https://doi.org/10.1007/978-1-4613-3739-3_7

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-3741-6

  • Online ISBN: 978-1-4613-3739-3

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