Control of UVB immunosuppression in the mouse by autosomal and sex-linked genes.
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 x 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 x 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 (Uvs1b/Uvs1b) 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.
Noonan
F P
FP
Department of Dermatology, George Washington University School of Medicine, Washington, DC 20037.
Hoffman
H A
HA
D000818:Animals; D003877:Dermatitis, Contact / Q000276:immunology*; D004843:Epistasis, Genetic; D005260:Female; D005796:Genes; D008040:Genetic Linkage; D007111:Immunity, Cellular / Q000528:radiation effects*; D007165:Immunosuppression Therapy; D008297:Male; D051379:Mice / Q000235:genetics / Q000276:immunology*; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D014466:Ultraviolet Rays; D014960:X Chromosome