Aod1, the immunoregulatory locus controlling abrogation of tolerance in neonatal thymectomy-induced autoimmune ovarian dysgenesis, maps to mouse chromosome 16.
Aod1, the immunoregulatory locus controlling abrogation of tolerance in neonatal thymectomy-induced autoimmune ovarian dysgenesis, maps to mouse chromosome 16.
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Aod1 是控制新生儿胸腺切除引起的自身免疫性卵巢发育不全耐受性消除的免疫调节位点，定位于小鼠 16 号染色体。
DOI：
10.1073/pnas.92.11.4758
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发表时间：
1995
影响因子：
11.1
通讯作者：
Griffith,JS
中科院分区：
文献类型：
--
作者：
Wardell,BB;Michael,SD;Tung,KS;Todd,JA;Blankenhorn,EP;McEntee,K;Sudweeks,JD;Hansen,WK;Meeker,ND;Griffith,JS
在三日龄（D3 Tx）时切除胸腺的小鼠在成年期间发展出多种器官特异性自身免疫性疾病，包括自身免疫性卵巢发育不全（AOD）。AOD的表型谱的特征在于抗卵巢自身抗体、卵巢炎和萎缩的发展。AOD的D3 Tx模型是独特的，因为疾病诱导完全取决于正常发育的免疫系统的扰动，是T细胞介导的，并且是菌株特异性的。例如，D3 Tx A/J小鼠对AOD高度敏感，而C57 BL/6 J小鼠具有抗性。在D3 Tx之后，以生理水平表达的自身卵巢抗原触发能够引发疾病的自身免疫应答。因此，D3 Tx模型提供了关注与疾病发病机制相关的自身耐受机制的机会。以往的研究表明，参与AOD易感性的主要机制是遗传控制和管理与外周耐受的诱导和维持相关的发育过程。我们在这里报告的映射的Aod 1基因座小鼠染色体16的区域内编码几个基因座的免疫相关性，包括scid，Igl 1，VpreB，Igll，Igl 1 r，Mtv 6（Mls-3），Ly-7，Ifnar，和Ifgt。
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 of AOD is characterized by the development of anti-ovarian autoantibodies, oophoritis, and atrophy. The D3Tx model of AOD 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 the mechanisms of self-tolerance that are relevant to disease pathogenesis. Previous studies indicate that the principal mechanisms involved in AOD susceptibility are genetically controlled and govern developmental processes associated with the induction and maintenance of peripheral tolerance. We report here the mapping of the Aod1 locus to mouse chromosome 16 within a region encoding several loci of immunologic relevance, including scid, Igl1, VpreB, Igll, Igl1r, Mtv6 (Mls-3), Ly-7, Ifnar, and Ifgt.