Autoimmune Ovarian Failure: Comparing the Mouse Model and the Human DiseaseIntramural Research Program, Gynecologic Endocrinology Unit, Section on Women's Health Research, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland; lawrence_nelson{at}nih.gov The neonatal-thymectomy—induced mouse model of autoimmune oophoritis has two important similarities with human autoimmune oophoritis. First, in both cases there is some defect in the immune system that permits the development of organ-specific autoimmunity. Second, in both there is some ovarian target under attack. In neither case do we fully understand the nature of the immune defect or the ovarian target. Because of its strong analogy with the human disease, murine experimental postthymectomy autoimmune oppohoritis may provide insight into the pathogenesis of autoimmune premature ovarian failure in women. Such studies may open new avenues toward the development of specific diagnostic and therapeutic methods. The histologic distribution of the ovarian lymphocytic infiltration is similar in the mouse and the human, and both mice and women with the disorder have reduced natural killer cell activity. Furthermore, susceptibility in both mice and women appears to be associated with genes outside the major histocompatibility complex. Finally, the mouse disorder is associated with a persistent neonatal-like Th2 response that suggests possible similarities with autoimmune polyglandular failure type 1 in humans. There is no currently available validated serum antibody marker that will confirm a clinical diagnosis of autoimmune premature ovarian failure. While investigating this animal model we cloned a novel gene that encodes an ooplasm-specific antigen associated with autoimmune oophoritis in mice. Based on its role in preimplantation development, we have designated this antigen Maternal Antigen That Embryos Require (MATER). MATER provides a new determinant with which to investigate the mechanisms of autoimmune premature ovarian failure.
Key Words: Autoimmunity • premature ovarian failure • autoantibody • thymectomy • mouse
Journal of the Society for Gynecologic Investigation, Vol. 8, No. 1 suppl,
S55-S57 (2001) |
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