Aod1, the immunoregulatory locus controlling abrogation of tolerance in neonatal thymectomy-induced autoimmune ovarian dysgenesis, maps to mouse chromosome 16.

Abstract

Mice thymectomized at three days of age (D3Tx) develop during adulthood a variety of organ-specific autoimmune diseases, including autoimmune ovarian dysgenesis (AOD). The phenotypic spectrum ofAOD is characterized by the development ofanti-ovarian autoantibodies, oophoritis, and atrophy. The D3Tx model ofAOD is unique in that disease induction depends exclusively on perturbation of the normal developing immune system, is T-cell-mediated, and is strain specific. For example, D3Tx A/J mice are highly susceptible to AOD, whereas C57BL/6J mice are resistant. After D3Tx, self ovarian antigens, expressed at physiological levels, trigger an autoimmune response capable of eliciting disease. The D3Tx model provides, therefore, the opportunity to focus on

A non-MHC locus essential for autoimmune type I diabetes in the Komeda Diabetes-Prone rat.

“…Aod1, involved in neonatal thymectomy-induced autoimmune ovarian dysgenesis, has been mapped on mouse Chr 16 (25). The map position of Aod1 seemed to be proximal to Gap43 (25), while Iddm/ kdp1 would be located in the region distal to Gap43, which weakened a possible relationship between Aod1 and Iddm/ kdp1.…”

“…Aod1, involved in neonatal thymectomy-induced autoimmune ovarian dysgenesis, has been mapped on mouse Chr 16 (25). The map position of Aod1 seemed to be proximal to Gap43 (25), while Iddm/ kdp1 would be located in the region distal to Gap43, which weakened a possible relationship between Aod1 and Iddm/ kdp1. The others include Ly7 (lymphocyte antigen-7), CD80 (CD80 antigen, also known as CD28 antigen ligand 1 or B7-1 antigen), CD47 (CD47 antigen, also known as Rh-related antigen, integrin-associated protein, or MER6 antigen identified by mAb 1D8), and MOX2 (antigen identified by mAb MRC OX-2) (24,26).…”

Premature Ovarian Failure and Ovarian Autoimmunity

“…PREMATURE OVARIAN FAILURE AND OVARIAN AUTOIMMUNITYthymectomy day 3 (284). This so-called Aod1 locus was associated with the presence of oö phoritis in the mice.…”

“…Interestingly, the markers on chromosome 16 failed to exhibit a significant linkage to the concomitant ovarian atrophy in this mouse oö phoritis model. Rather, this atrophy exhibited an association with markers on mouse chromosome 3 (284). With regard to another experimental mouse model of gonadal autoimmunity, viz the male counterpart of allergic oö phoritis, experimental allergic orchitis, studies have shown a similar complexity of gene involvement and the recognition of various susceptibility and resistance loci (the Orch genes) (285).…”

Interacting Quantitative Trait Loci Control Loss of Peripheral Tolerance and Susceptibility to Autoimmune Ovarian Dysgenesis After Day 3 Thymectomy in Mice

“…Silveira et al (8) showed that two loci on chromosome 4, Gasa1 and Gasa2, control susceptibility to autoimmune gastritis after D3Tx. In a previous study, we reported that susceptibility to autoimmune ovarian dysgenesis (AOD) is controlled by loci on chromosome 16 (Aod1) and chromosome 3 (Aod2) (9,10).…”