Immunization with thyroglobulin induces Graves'-like disease in mice.
Immunization with thyroglobulin induces Graves'-like disease in mice.
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DOI：
10.1677/joe-09-0089
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发表时间：
2009-08
期刊：
影响因子：
--
通讯作者：
Kobayashi T
中科院分区：
文献类型：
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作者：
Endo T;Kobayashi T
我们用牛甲状腺球蛋白（Tg）每2周免疫一次AKR/N小鼠，并监测其甲状腺中125I摄取活性的时间依赖性变化。3个月后，免疫小鼠血清抗tg抗体均呈阳性。免疫小鼠（n=6）血清游离三碘甲状腺原氨酸（T3）和游离甲状腺素（T4）水平显著高于注射生理盐水小鼠（n=6）。颈部计数和甲状腺显像显示，免疫小鼠的碘摄取活性没有受到抑制，反而比对照组小鼠高。6只免疫小鼠中有2只表现出极高的碘吸收活性。两组小鼠甲状腺弥漫性增大，上皮细胞高度增高。此外，两只具有高碘吸收活性的小鼠产生了高滴度的促甲状腺抗体。进一步的实验表明，11只AKR/N小鼠中有4只和10只C57BL6小鼠中有3只免疫Tg后血清游离T3/游离T4水平高，甲状腺125I摄取活性高，促甲状腺抗体活性阳性。弥漫性甲状腺肿、甲状腺毒症、高碘吸收活性、促甲状腺抗体阳性是Graves病的特征。因此，这些老鼠表现出格雷夫斯病的症状。这些结果表明，Tg免疫可诱导小鼠Graves‘样病，本方法将为Graves’病提供一种新的动物模型。
We immunized AKR/N mice with bovine thyroglobulin (Tg) once every 2 weeks and monitored their time-dependent changes in 125I uptake activity in the thyroid glands. After 3 months, anti-Tg antibody was positive in all sera from the immunized mice. Serum free tri-iodothyronine (T3) and free thyroxine (T4) levels in the immunized mice (n=6) were significantly higher than those in the saline injected (control) mice (n=6). Neck counts as well as scintigraphy of the thyroid glands revealed that iodide uptake activity of the immunized mice was not suppressed, but was instead higher than that of the control mice. Two of the six immunized mice showed extremely high iodide uptake activity. The thyroid glands of these two mice were diffusely enlarged and the height of the epithelial cells was also increased. In addition, two mice with high iodide uptake activity produced a high titer of thyroid-stimulating antibody. Additional experiments showed that 4 out of 11 AKR/N mice and 3 out of 10 C57BL6 mice immunized with Tg had high serum free T3/free T4 levels, high 125I uptake activity of the thyroid, and positive thyroid-stimulating antibody activity. Diffuse goiter, thyrotoxicosis, high iodide uptake activity, and positive thyroid-stimulating antibody are the characteristics of Graves' disease. Thus, these mice exhibit the symptoms of Graves' disease. These results suggest that immunization with Tg induces Graves'-like disease in mice and that our methods will provide a new animal model of Graves' disease.