Irradiation with ultraviolet B (UVB; 290-320 nm) initiates systemic immunosuppression of contact hypersensitivity (CHS). UV dose-responses for suppression of CHS to trinitrochlorobenzene were established in 18 strains of inbred mice. Three phenotypes with significantly different susceptibilities to UV suppression were identified. The phenotypes were: high (HI) susceptibility, 50% suppression with 0.7-2.3 kJ/m2 UV (C57BL/6, C57BL/10, and C57L and NZB females); low (LO) susceptibility, 50% suppression with 9.6-12.3 kJ/m2 UV (BALB/c, AKR, SJL and NZW), and intermediate (INT) susceptibility, 50% suppression with 4.7-6.9 kJ/m2 UV (DBA/2, C57BR, C3H/HeJ, C3H/HeN, CBA/N and A/J). UV suppression was not correlated with skin pigmentation or with the magnitude of the CHS response in non-irradiated animals. Major histocompatibility complex (MHC) haplotype was not correlated with UV suppression in MHC congenic strains B10.D2/oSnJ, B10.D2/nSnJ, B10.BR/SgSnJ, and A.BY/SnJ. There were no sex differences in UV suppression in BALB/c, C57BL/6, or NZW animals. In the autoimmune NZB strain, however, male mice (LO) were seven times less sensitive to UV suppression than NZB female mice (HI). Both sexes of (NZB x NZW)F1 and (NZW x NZB)F1 mice were HI, supporting dominance of HI over LO. Thus there are genetic factors and interacting sex-limited factors determining susceptibility to UV suppression. These findings may be of relevance to UV-related diseases such as photosensitive lupus and skin cancer.

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.

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The level of liver catalase activity in substrain C57BL/6 mice is only approximately half that in substrain C57BL/He. That this difference was due to a single major gene with low level of activity dominant to high was indicated by analysis of the F1, F2, and backcross hybrids and confirmed by progeny tests of first back-cross male segregants. The gene symbol Ce is suggested.The absence of any difference between reciprocal hybrids indicated no extra-chromosomal maternal influence.There was no evidence that this gene controlling liver catalase had any influence on the level of kidney catalase activity for this did not vary between the two parent substrains or the hybrid groups.Males consistently had higher liver and kidney catalase activity than females. The difference was more pronounced in respect to kidney catalase, males having about twice the activity found in females.