Abstract
The functional activity of natural killer (NK) cells has been found to be modulated by several point mutations associated with coat color. The most commonly studied gene, beige (Bg), has been found to block a postrecognition event in the lytic cycle. Four other coat color mutations in the mouse (satin, leaden, fuzzy, pale ears) were studied for their effect on NK cell function, and only one, satin (Sa), was found to be suppressive. When both the Sa and Bg mutations were present in the same animal, their effects were synergistic in the suppression of NK levels. Normal numbers of NK cells were present in these double mutants, as determined by the frequency of IgG2b binding cells and by antiasialo GM1 staining. The ability of Sa/Bg NK cells to recognize and bind targets suggests that the defect is localized in the postbinding cytolytic pathway. These genes were not specific for NK cells and also suppressed alloimmune cytolytic T lymphocyte function. Since Sa/Bg mice are much more suppressed in NK function than Bg mice, we suggest that this double mutant may be a better model for NK deficiency in vivo.
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Abo, T., Roder, J., Abo, W., Cooper, M., and Balch, C. M.: Natural killer (HNK-1+) cells in Chediak Higashi patients are present in normal numbers but are abnormal in function and morphology. J. Clin. Invest. 70: 193–197, 1982
Beaumont, T. J., Roder, J. C., Elliott, B., Kerbel, R. S., Dennis, J. W., Kasai, M., and Okumura, K.: A comparative analysis of cell surface markers on murine NK cells and CTL target-effector conjugates. Scand. J. Immunol. 16: 123–133, 1982
Clark, E. A., Shultz, L. D., and Pollack, S. B.: Mutations in mice that influence natural killer (NK) cell activity. Immunogenetics 12: 601–613, 1981
Clark, E. A., Roths, J. B., Murphy, E. D., Ledbetter, J. A., and Clagett, J. A.: The beige (Bg) gene influences the development of autoimmune disease in SB/Le male mice. In R. B. Herberman (ed.): NK Cells and Other Natural Effector Cells, Volume 2, pp. 301–312, Academic Press Inc., New York, 1982
Currie, C.: Cytotoxic Studies on Immunosuppressed Mice, M. Sc. thesis, Department of Microbiology, Queens's University Kingston, Ontario, Canada, 1984
Gorelik, E., Wiltrout, R. H., Okumura, K., Hahn, S., and Herberman, R. B.: Role of natural killer cells in the control of metastatic spread and growth of tumor cells in mice. Int. J. Cancer 30: 107–112, 1982
Green, E. L.: The Biology of the Laboratory Mouse, McGraw-Hill, New York, New York, 1966
Hanna, N. and Burton, R. C.: Definitive evidence that natural killer (NK) cells inhibit experimental tumour metastasis in vivo. J. Immunol. 127: 1754–1758, 1981
Hanna, N. and Schneider, M.: Enhancement of tumour metastasis and suppression of natural killer cell activity by B-Estradiol treatment. J. Immunol. 130: 974–980, 1983
Karre, K.: In Vivo Relevance of Natural Killer Cells, Ph. D. thesis, Dept. of Tumor Biology, Karolinska Institute, Stockholm, Sweden, 1981
Karre, K., Klein, G. O., Kiessling, R., Klein, G., and Roder, J. C.: Low natural in vivo resistance to syngeneic leukemias in natural killer cell-deficient mice. Nature 284: 624–626, 1980
Kasai, M., Leclerc, J. C., McVay-Boudreau, L., Shen, F. W., and Cantor, H.: Direct evidence that natural killer cells in nonimmune spleen cell populations prevent tumour growth in vivo. J. Exp. Med. 149: 1264–1264, 1979
Kiessling, R. and Haller, O.: Natural killer cells in the mouse: An alternative immune surveillance mechanism? Contemp. Top. Immunobiol. 8: 171–201, 1978
Kiessling, R., Klein, E., Pross, H., and Wigzell, H.: “Natural” killer cells in the mouse. II. Cytotoxic cells with specificity for Moloney leukemia cells. Characteristics of the killer cell. Eur. J. Immunol. 5: 117–121, 1975
Lauzon, R., Haliotis, T., and Roder, J. C.: The in vivo role of NK cells in anti-tumor surveillance. In G. Mathe and P. Reizenstein (eds.): Pathophysiological Aspects of Cancer Epidemiology: Immunological, Virological, Endocrinological and Genetical Factors, in press, Pergamon Press, Oxford, 1984
Loutit, J. F., Townsend, K. M. S., and Knowles, J. F.: Tumour surveillance in beige mice. Nature 285: 66, 1981
McGarry, R. C. and Roder, J. C.: Interaction of natural killer cells and viruses. J. Leuk. Biol., in press, 1984
McKinnon, K. P., Hale, A. H., and Ruebush, M. J.: Elicitation of natural killer cells in beige mice by infection with vesicular stomatitis virus. Infect. Immun. 32: 204–210, 1981
Roder J. C. and Duwe, A. K.: The beige mutation in the mouse selectively impairs natural killer cell function. Nature 278: 451–453, 1979
Roder, J. C. and Haliotis, T.: Do NK cells play a role in anti-tumor surveillance? Immunol. Today. 1: 96–100, 1980
Roder, J. C. and Kiessling, R.: Target-effector interaction in the natural killer cell system. I. Co-variance and genetic control of cytolytic and target cell binding. Scand. J. Immunol. 8: 135–144, 1978
Roder, J. C. and McGarry, R. C.: Genes that control natural killer cell function in man and mouse. In R. Crispen (eds.): Chicago Symposium: Cancer Etiology and Prevention, pp. 12140, Elsevier Biomedical Press, New York, 1983
Roder, J. C., Kiessling, R., Biberfield, P., and Andersson, B.: Target-effector interaction in the natural killer cell system. II. The isolation of NK cells and studies on the mechanism of killing. J. Immunol. 121: 2509–2517, 1978
Roder, J. C., Lohmann-Matthes, M. L., Domzig, W., and Wigzell, H.: The beige mutation in the mouse. II. Selectivity of the natural killer cell defect. J. Immunol. 123: 2174–2181, 1979
Roder, J. C., Haliotis, T., Klein, M., Korec, S., Jett, J., Ortaldo, J., Herberman, R. B., Katz, P., and Fauci, A. S.: A new immunodeficiency disorder in humans involving NK cells. Nature 248: 553–555, 1980a
Roder, J. C., Argov, S., Klein, M., Petersson, C., Kiessling, R., Andersson, K., and Hansson, M.: Target-effector interaction in the natural killer cell system. V. Energy requirements, protein synthesis and the possible involvement of lysosomal enzymes. Immunology 40: 107–116, 1980b
Saxena, R., Saxena, Q., and Adler, W. H.: Defective T-cell response in beige mutant mice. Nature: 240–241, 1982
Warner, J. F. and Dennert, G.: Effects of a cloned line with natural killer cell activity on bone marrow transplants, tumour development and metastasis in vivo. Nature 300: 31–34, 1982
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McGarry, R.C., Walker, R. & Roder, J.C. The cooperative effect of the Satin and Beige mutations in the suppression of NK and CTL activities in mice. Immunogenetics 20, 527–534 (1984). https://doi.org/10.1007/BF00364355
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DOI: https://doi.org/10.1007/BF00364355