Susceptibility to Murine Experimental Autoimmune Oophoritis Is Associated With Genes Outside the Major Histocompatibility Complex (MHC)


Section on Gynecologic Research, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892.


PROBLEM: Neonatal thymectomy induces experimental autoimmune oophoritis in certain strains of mice, and this serves as a model for human autoimmune oophoritis. Because strong MHC associations have been noted in human autoimmune conditions, we investigated the role of MHC in determining susceptibility to murine experimental autoimmune oophoritis. Strain A mice are highly susceptible to post-thymectomy autoimmunity, whereas strain B10 mice are relatively resistant. The availability of congenic strains of mice makes it possible to separate the effects of genetic background and specific H-2 haplotype.

METHODS: We neonatally thymectomized A and B10 background female mice, and their H-2 congenic counterparts, and then evaluated the resulting ovarian disease at age 6 weeks. RESULTS: A. By mice, which have the A background and the H-2b haplotype, developed severe disease equivalent to strain A mice. Similarly, B10.A mice, which have the B background and the H-2a haplotype, failed to develop disease. Thus, H-2a haplotype did not convey disease susceptibility.

CONCLUSIONS: Our findings suggest that immune-regulatory regions outside the H-2 locus play an important role in determining susceptibility to murine post-thymectomy autoimmune oophoritis. This is in accord with our previous findings in women that showed no association between MHC and premature ovarian failure. Thus, in this respect this model is similar to human autoimmune ovarian failure. This suggests that the non-MHC genes conveying susceptibility to autoimmune oophoritis in mice might represent similar predisposing genes for premature ovarian failure in women.