CONTROL OF UVB IMMUNOSUPPRESSION IN THE MOUSE BY AUTOSOMAL AND SEX-LINKED GENES

Irradiation with UVB (290-320 nm) initiates a systemic immunosuppressi on detectable as suppression of contact hypersensitivity (CHS). We inv estigated susceptibility to UV suppression in reciprocal F-1-hybrid an d backcross mice derived from BALB/c (low susceptibility) and C57BL/6 (high susceptibility) inbred strains. CBBF1 male mice exhibited high s usceptibility and B6CF(1) male mice exhibited low susceptibility, indi cating a major X-linked effect in the genetic control of UV immune sup pression. Females of either F-1 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 geneti cally unlinked autosomal genes was found in parental backcross animals . Both sexes of (BALB/c x CBGF(1)) mice showed a 1 high:1 low ratio of phenotypes, indicating control by a major autosomal locus, Uvs1, conf irmed by propagation of the high phenotype through selective backcross ing for nine generations to BALB/c. Uvs1 was not genetically linked to 12 chromosomal markers including the pigment genes b (brown) and c (a lbino). Backcross animals (C57BL/6 x CB6F(1)) showed a significant sex difference, male mice giving a 3 high: 1 low ratio of phenotypes, com patible with the action of a second autosomal locus, Uvs2, in this hyb rid. 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 find ing of genetic control by interacting autosomal and X-linked genes is unique. Genetically determined high susceptibility to UV immunosuppres sion may be an important risk factor for UV-related human diseases.