HIGH-INCIDENCE OF THYROIDITIS AND ANTITHYROID AUTOANTIBODIES IN NOD MICE
HIGH-INCIDENCE OF THYROIDITIS AND ANTITHYROID AUTOANTIBODIES IN NOD MICE
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DOI：
10.2337/diabetes.41.1.40
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发表时间：
1992-01-01
期刊：
影响因子：
7.7
通讯作者：
MARGOLESE, H
中科院分区：
文献类型：
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作者：
BERNARD, NF;ERTUG, F;MARGOLESE, H
NOD 小鼠患上自发性胰岛素依赖型糖尿病 (IDDM)，与单核细胞浸润胰岛有关。胰岛浸润导致分泌胰岛素的β细胞的自身免疫性破坏。由于人类和 BB 大鼠的糖尿病通常与自身免疫性甲状腺疾病 (ATD) 相关，因此对 NOD 小鼠模型进行了检查，以寻找甲状腺炎和与小鼠甲状腺膜抗原 (MTMA) 反应的血清抗体的证据。 180日龄以上小鼠甲状腺炎发病率为77%，61-180日龄小鼠甲状腺炎发病率为67%，31-60日龄小鼠甲状腺炎发病率为72%，21-30日龄小鼠甲状腺炎发病率为74%，11-20日龄小鼠甲状腺炎发病率为78%，小于或等于10日龄小鼠甲状腺炎发病率为90%。小于或等于 30 天龄的 NOD 小鼠的甲状腺炎程度低于大于 180 天龄的动物。接受测试的任何其他年龄组之间的甲状腺炎严重程度没有显着差异。与非糖尿病动物相比，糖尿病动物的甲状腺炎发病率并未增加，也未发现甲状腺炎与性别之间存在关联。小于或等于 30 日龄的年龄组中甲状腺炎的高发病率表明，在该模型中，淋巴细胞浸润甲状腺可能先于胰岛炎的发生。尽管 NOD 小鼠的甲状腺炎和胰岛素炎都很早就开始（分别在生命的第一个月和第二个月），但在个体小鼠中没有发现这两个器官的浸润之间存在显着关联。 35% 的 NOD 小鼠体内存在针对 MTMA 的循环抗体。患有甲状腺炎的 NOD 小鼠中发现抗 MTMA 抗体的频率明显高于没有单核细胞浸润的小鼠。这种特异性的抗体出现在糖尿病发病之前，并且可能继发于单核细胞介导的甲状腺细胞损伤，尽管这一点尚未得到证实。 NOD小鼠除了是IDDM的优秀动物模型外，还可以作为ATD模型进行研究。此外，NOD 小鼠可能有助于探索糖尿病和 ATD 之间关联的根本原因。
NOD mice develop spontaneous insulin-dependent diabetes mellitus (IDDM) associated with infiltration of pancreatic islets with mononuclear cells. Islet infiltration results in autoimmune destruction of insulin-secreting beta-cells. Because in humans and BB rats diabetes is often associated with autoimmune thyroid disease (ATD), the NOD mouse model was examined for evidence of thyroiditis and serum antibodies reactive with mouse thyroid membrane antigens (MTMAs). The incidence of thyroiditis was 77% in mice > 180 days old, 67% in mice 61-180 days old, 72% in mice 31-60 days old, 74% in mice 21-30 days old, 78% in mice 11-20 days old, and 90% in mice less-than-or-equal-to 10 days old. NOD mice less-than-or-equal-to 30 days old had less-severe thyroiditis than animals > 180 days old. There was no significant difference in severity of thyroiditis between any of the other age-groups tested. The incidence of thyroiditis was not increased in diabetic compared with nondiabetic animals, nor was an association found between thyroiditis and sex. The high incidence of thyroiditis in the less-than-or-equal-to 30-day-old age-group indicates that infiltration of lymphocytes into the thyroid can precede initiation of insulitis in this model. Although both thyroiditis and insulitis in NOD mice began early (by the lst and 2nd mo of life, respectively), no significant association between infiltration of these two organs was noted in individual mice. Circulating antibodies to MTMA were demonstrated in 35% of NOD mice. Anti-MTMA antibodies were found significantly more frequently in NOD mice with thyroiditis than in those without mononuclear cell infiltration. Antibodies of this specificity precede the onset of diabetes and are likely to be secondary to mononuclear cell-mediated thyroid cell damage, although this has not been proven. The NOD mouse, in addition to being an excellent animal model for IDDM, can also be studied as a model for ATD. In addition NOD mice may be useful for exploring the underlying cause of the association between diabetes and ATD.