Abstract
Irradiation with UVB (290–320 nm) initiates a systemic immunosuppression detectable as suppression of contact hypersensitivity (CHS). We investigated susceptibility to UV suppression in reciprocal F1-hybrid and backcross mice derived from BALB/c (low susceptibility) and C57BL/6 (high susceptibility) inbred strains. CB6F1 male mice exhibited high susceptibility and B6CF1 male mice exhibited low susceptibility, indicating a major X-linked effect in the genetic control of UV immune suppression. Females of either F1 hybrid showed intermediate suppression, consistent with random X-inactivation. A model of monogenic X-linked control was not sufficient, and evidence for the action of two genetically unlinked autosomal genes was found in parental backcross animals. Both sexes of (BALB/c × CB6F1) mice showed a 1 high: 1 low ratio of phenotypes, indicating control by a major autosomal locus, Uvs1, confirmed by propagation of the high phenotype through selective backcrossing for nine generations to BALB/c. Uvs1 was not genetically linked to 12 chromosomal markers including the pigment genes b (brown) and c (albino). Backcross animals (C57BL/6 × CB6F1) showed a significant sex difference, male mice giving a 3 high: 1 low ratio of phenotypes, compatible with the action of a second autosomal locus, Uvs2, in this hybrid. The findings are compatible with a model in which high phenotype (Uvs1 b/Uvs1 b) is dominant when subjected to recessive epistatis by the X-chromosome locus Uvs3, or by the autosomal locus Uvs2. The finding of genetic control by interacting autosomal and X-linked genes is unique. Genetically determined high susceptibility to UV immunosuppression may be an important risk factor for UV-related human diseases.
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References
Armstrong, B. K. and English, D. R. Epidemiologic studies. In C. M. Balch, A. N. Houghton, G. W. Milton, A. J. Sober, and S.-J. Soongs (eds.): Cutaneous Melanoma: Second Edition, pp. 12–26 J. B. Lippincott, Philadelphia, 1992
Ballabio, A. and Willard, H. F. Mammalian X-chromosome inactivation and the XIST gene. Curr Opin Genet Dev 2: 439–447, 1992
Cooper, K. D., Oberhelman, L., Hamilton, T. A., Baadsgaard, O., Terhune, M., Levee, G., Anderson, T., and Koren, H. UV exposure reduced immunization rates and promotes tolerance to epicutaneous antigens in humans-relationship to dose, CD1a-DR+ epidermal macrophage induction and Langerhans cell depletion. Proc Natl Acad Sci USA 89: 8497–8501, 1992
Crow, M. K. and Christian, C. L. Etiologic hypotheses for systemic lupus erythematosus. In R. G. Lahitas (ed.): Systemic Lupus Erythematosus, pp. 51–64, Churchill Livingstone, New York, 1992
De Fabo, E. C. and Kripke, M. L. Dose-response characteristics of immunologic unresponsiveness to UV-induced tumors produced by UV irradiation of mice. Photochem Photobiol 30: 385–390, 1979
De Fabo, E. C. and Kripke, M. L. Wavelength dependence and dose-rate independence of UV radiation induced suppression of immunologic unresponsiveness of mice to a UV-induced fibrosarcoma. Photochem Photobiol 32: 183–188, 1980
De Fabo, E. C. and Noonan, F. P. Mechanism of immune suppression by UV irradiation in vivo. I. Evidence for the existence of a unique photoreceptor in the skin and its role in photoimmunology. J Exp Med 158: 84–98, 1983
De Fabo, E. C., Noonan, F. P., and Frederick, J. E. Biologically effective doses of sunlight for immune suppression at various latitudes and their relationship to changes in stratospheric ozone. Photochem Photobiol 52: 811–817, 1990
Fisher, M. S. and Kripke, M. L. Systemic alteration induced in mice by ultraviolet light irradiation and its relationship to ultraviolet carcinogenesis. Proc Natl Acad Sci USA 74: 1688–1692, 1977
Geisser, S. Posterior odds for multivariate normal classification. J R Statist Soc Series B 26: 69–76, 1964
Giannini, M. S. H. Suppression of pathogenesis in cutaneous Leishmaniasis by UV irradiation. Infect Immun 51: 838–843, 1986
Green, M. C. Methods for testing linkage. In W. J. Burdette (ed.): Methodology in Mammalian Genetics, pp. 56–82, Holden-Day, San Francisco, 1963
Greene, M. I., Sy, M. S., Kripke, M. L., and Benacerraf, B. Impairment of antigen-presenting function by ultraviolet radiation. Proc Natl Acad Sci USA 76: 6592–6595, 1979
Harris, H. and Hopkinson, D. A. Handbook of Enzyme Electrophoresis in Human Genetics, North Holland Publishing, Amsterdam, 1970
Hersey, P., Hasic, E., Edwards, A., Bradley, M., and Haran, G. Immunological effects of solarium exposure. Lancet 1: 545–548, 1983
Heston, W. E., Hoffman, H. A., and Rechcigl, M. Genetic analysis of liver catalase activity in two substrains of C57BL mice. Genet Res 6: 387–397, 1965
Hoffman, H. A. Starch-gel electrophoresis of murine major urinary protein. Proc Soc Exp Biol 135: 81–83, 1970
Hoffman, H. A. Biochemical markers. In T. Nomura, H. Esaki, and T. Tomita (eds.): ICLAS Manual for Genetic Monitoring of Inbred Mice, pp. 38–90, University of Tokyo Press, Tokyo, 1984
Howie, S. E. M., Norval, M., and Maingay, J. Exposure to low-dose ultraviolet radiation suppresses delayed-type hypersensitivity to Herpes Simplex in mice. J Invest Dermatol 86: 125–128, 1986
Jeevan, A. and Kripke, M. L. Effect of a single exposure to ultraviolet radiation on Mycobacterium bovis Bacille Calmette Guerin infection in mice. J Immunol 143: 2837–2843, 1989
Kalimo, K., Koulu, L., and Jansen, C. T. Effect of a single UVB or PUVA exposure on immediate and delayed skin hypersensitivity reactions in humans. Arch Dermatol Res 275: 374–378, 1983
Lyon, M. F. Gene action in the X-chromosome of the mouse (Mus musculus). Nature 190: 372, 1961
Noonan, F. P. and De Fabo, E. C. Ultraviolet-B dose-response curves for local and systemic immunosuppression are identical. Photochem Photobiol 52: 801–810, 1990
Noonan, F. P. and De Fabo, E. C. Immunosuppression by ultraviolet B radiation: initiation by urocanic acid. Immunol Today 13: 250–254, 1992
Noonan, F. P., De Fabo, E. C., and Kripke, M. L. Suppression of contact hypersensitivity by UV radiation and its relationship to UV-induced suppression of tumor immunity. Photochem Photobiol 34: 683–690, 1981
Noonan, F. P. and Hoffman, H. A. Susceptibility to immunosuppression by ultraviolet B radiation in the mouse. Immunogenetics 39: 29–39, 1994
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Noonan, F.P., Hoffman, H.A. Control of UVB immunosuppression in the mouse by autosomal and sex-linked genes. Immunogenetics 40, 247–256 (1994). https://doi.org/10.1007/BF00189969
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DOI: https://doi.org/10.1007/BF00189969