A major role for non-major histocompatibility complex genes but not for microorganisms in a novel murine model of Graves' hyperthyroidism
A major role for non-major histocompatibility complex genes but not for microorganisms in a novel murine model of Graves' hyperthyroidism
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DOI：
10.1089/105072503321582024
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发表时间：
2003-03-01
期刊：
影响因子：
6.6
通讯作者：
Niwa, M
中科院分区：
文献类型：
--
作者：
Nagayama, Y;McLachlan, SM;Niwa, M
Graves病的病因是多因素的。我们使用一种新的小鼠模型研究遗传和环境因素对Graves甲亢易感性的作用。肌内注射表达促甲状腺激素受体的重组腺病毒（AdCMVTSHR）可诱导超过50%的雌性BALB/c小鼠出现Graves样甲状腺功能亢进（促甲状腺激素受体[TSHR]抗体、甲状腺素升高和弥漫性甲状腺肿）。用AdCMVTSHR免疫BALB/c（H-2d）、BALB.K（H-2k）和DBA/2 J（H-2d）小鼠，研究主要组织相容性复合体（MHC）和非MHC基因在甲亢易感性中的相对作用。大约50%的BALB/c和BALB.K小鼠出现甲状腺功能亢进，但DBA/2 J小鼠仅为5%，表明非MHC基因在疾病发展中起主要作用。环境微生物的影响进行了评估，通过比较疾病的发病率在BALE/c小鼠保持在无病原体的条件下与那些在非无菌，传统的住房，以及通过共同管理的微生物成分（大肠杆菌脂多糖或酵母酵母菌多糖A）作为佐剂与AdCMVTSHR。这两种类型的暴露于环境病原体的影响疾病的诱导。总之，非MHC基因，而不是传染性生物体，发挥了重要作用，这种新的小鼠模型的Graves病的病因。
The etiology of Graves' disease is multifactorial. We investigated the role of genetic and environmental factors on the susceptibility to Graves' hyperthyroidism using a new murine model. Intramuscular injection of recombinant adenovirus expressing the thyrotropin receptor (AdCMVTSHR) induces Graves'-like hyperthyroidism (thyrotropin receptor [TSHR] antibodies, elevated thyroxine, and diffuse goiter) in more than 50% of female BALB/c mice. The relative contributions of major histocompatibility complex (MHC) and non-MHC genes on the susceptibility to hyperthyroidism were studied by immunizing BALB/c (H-2d), BALB.K (H-2k), and DBA/2J (H-2d) mice with AdCMVTSHR. Hyperthyroidism developed in approximately 50% of BALB/c and BALB.K mice but only 5% of DBA/2J mice, indicating a major role for non-MHC genes in disease development. The effect of environmental microorganisms was evaluated by comparing disease incidence in BALE/c mice maintained in pathogen-free conditions versus those in nonsterile, conventional housing, as well as by coadministering microorganism components (Escherichia coli lipopolysaccharide or yeast zymosan A) as adjuvants with AdCMVTSHR. Neither type of exposure to environmental pathogens influenced disease induction. In conclusion, non-MHC genes, but not infectious organisms, play a major role in the etiology of this novel murine model of Graves' disease.