AOD1, THE IMMUNOREGULATORY LOCUS CONTROLLING ABROGATION OF TOLERANCE IN NEONATAL THYMECTOMY-INDUCED AUTOIMMUNE OVARIAN DYSGENESIS, MAPS TO MOUSE CHROMOSOME-16

Mice thymectomized at three days of age (D3Tx) develop during adulthoo d a variety of organ-specific autoimmune diseases, including autoimmun e ovarian dysgenesis (AOD). The phenotypic spectrum of AOD is characte rized by the development of anti-ovarian autoantibodies, oophoritis, a nd atrophy. The D3Tx model of AOD is unique in that disease induction depends exclusively on perturbation of the normal developing immune sy stem, is T-cell-mediated, and is strain specific. For example, D3Tx A/ J mice are highly susceptible to AOD, whereas C57BL/6J mice are resist ant. After D3Tx, self ovarian antigens, expressed at physiological lev els, trigger an autoimmune response capable of eliciting disease. The D3Tx model provides, therefore, the opportunity to focus on the mechan isms of self-tolerance that are relevant to disease pathogenesis. Prev ious studies indicate that the principal mechanisms involved in AOD su sceptibility are genetically controlled and govern developmental proce sses associated with the induction and maintenance of peripheral toler ance, We report here the mapping of the Aod1 locus to mouse chromosome 16 within a region encoding several loci of immunologic relevance, in cluding scid, Igl1, VpreB, Igll, Igl1r, Mtv6 (Mls-3), Ly-7, Ifnar, and Ifgt.