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Chromosomal locations and gonadal dependence of genes that mediate resistance to ectromelia (mousepox) virus-induced
D G Brownstein1, P N Bhatt, L Gras
1Section of Comparative Medicine, Yale University School of Medicine, New Haven, Connecticut 06510.
Abstract:
Four genetic loci were tested for linkage with loci that control genetic resistance to lethal ectromelia virus infection in mice. Three of the loci were selected because of concordance with genotypes assigned to recombinant inbred (RI) strains of mice derived from resistant C57BL/6 and susceptible DBA/2 (BXD) mice on the basis of their responses to challenge infection. Thirty-six of 167 male (C57BL/6 x DBA/2)F1 x DBA/2 backcross (BC) mice died (22%), of which 27 (75%) were homozygous for DBA/2 alleles at Hc and H-2D. Twenty-eight percent of sham-castrated and 6% of sham-ovariectomized BC mice were susceptible to lethal mousepox, whereas 50% of gonadectomized mice were susceptible. There was no linkage evident between Hc or H-2D and loci that controlled resistance to lethal ectromelia virus infection in 44 castrated BC mice. Mortality among female mice of BXD RI strains with susceptible or intermediate male phenotypes was strongly correlated (r = 0.834) with male mortality. Gonadectomized C57BL/6 mice were as resistant as intact mice to lethal ectromelia virus infection. These results indicate that two gonad-dependent genes on chromosomes 2 and 17 and one gonad-independent gene control resistance to mousepox virus infection, that males and females share gonad-dependent genes, and that the gonad-independent gene is fully protective.
Insights
Genetic resistance to mousepox involves gonad-dependent genes on chromosomes 2 and 17, and a fully protective gonad-independent gene. Both sexes share the gonad-dependent genes, influencing ectromelia virus infection outcomes.
Area of Science:
- Immunogenetics
- Virology
- Mouse Genetics
Background:
- Ectromelia virus causes lethal mousepox, a significant disease model.
- Genetic factors influencing resistance to ectromelia virus infection are not fully understood.
- Recombinant inbred (RI) mouse strains (BXD) derived from resistant (C57BL/6) and susceptible (DBA/2) parents are valuable for genetic studies.
Purpose of the Study:
- To identify genetic loci controlling resistance to lethal ectromelia virus infection in mice.
- To investigate the role of gonad-dependent and independent genes in mousepox resistance.
- To determine the linkage of specific genetic loci (Hc and H-2D) with resistance traits.
Main Methods:
- Testing four genetic loci for linkage with resistance to lethal ectromelia virus infection.
- Utilizing (C57BL/6 x DBA/2)F1 x DBA/2 backcross (BC) mice and BXD RI strains.
- Analyzing mortality rates in sham-castrated, sham-ovariectomized, and gonadectomized mice.
- Correlating male and female mortality in BXD RI strains.
Main Results:
- Two gonad-dependent genes on chromosomes 2 and 17, and one gonad-independent gene control resistance.
- Males and females share the gonad-dependent genes.
- The gonad-independent gene provides complete protection against lethal ectromelia virus infection.
- No linkage was found between Hc or H-2D and resistance loci in castrated BC mice.
Conclusions:
- Mousepox resistance is controlled by a combination of sex-influenced and sex-independent genetic factors.
- Gonad-dependent genes play a crucial role in modulating susceptibility to ectromelia virus.
- The identified genetic loci provide targets for understanding host defense mechanisms against viral infections.