Graves病（GD）是一种常见的自身免疫性甲状腺疾病，机体产生促甲状腺素受体（TSHR）抗体是该病主要发病机理，但至今尚无针对其病因的有效治疗方法。建立GD动物模型是探索该病发病机制及防治方法有效工具。目前，以表达TSHR A亚单位重组腺病毒诱导的小鼠GD模型最为常用。但腺病毒表达目的基因持续时间短，需反复注射，易产生中和抗体而降低表达效率。此外小鼠遗传背景和人类相差较大，小鼠模型不能确切模拟人类GD疾病过程。因此，建立更为理想的动物模型至关重要。本课题拟在前期工作基础上，获取长期稳定表达TSHR A亚单位的重组腺相关病毒，以不同剂量免疫小鼠，探索诱导GD模型新方法，并在此基础上制备与人类基因背景更为相似的树鼩GD模型，评估成模效果，比较小鼠及树鼩GD模型在疾病特征，组织病理、淋巴细胞免疫功能、T细胞免疫组库及单细胞全转录组测序等方面异同，为GD发病机制、新的防治方法等研究提供最佳工具。

Graves’disease（GD）is a common autoimmune thyroid disease and the antibody of thyrotropin receptor (TSHR) against the body itself is the main pathogenesis , yet still without efficient therapies against its causes presently. It is an effective tool to build GD animal model to explore the pathogenesis or the prevention and treatment of the disease. Up to now, the most commonly used animal model is the mice GD model induced by recommended adenovirus expressing TSHR A subunit. However the target gene expressed by adenovirus can only sustain a short time, which needs repeated injection, furthermore the mice are liable to produce virus neutralizing antibody to reduce the expressing efficiency，that is unfavorable to establish the GD model . In addition, being obvious the difference of genetic background , the mice model cannot exactly simulate the process of humans GD. Therefore, it is of vitally important to build a more perfect GD animal model. On the basis of previous work, the recombinant adeno-associated viruses that can express TSHR A subunit stably in the long term will be obtained. Then the new method will be explored to induce GD model in the mice treated with these adeno-associated viruses in different doses. According to these data, GD model of tree shrews, more similar to human genetic background, are to be established. After that, the effects of the models of mice and tree shrews will be assessed, as well as similarities and differences of some aspects, such as disease characteristics, histological pathology, lymphocyte immune function, T cell immunerepertoire and single-cell transcriptome analysis, to provide an ideal tool to investigate Graves’ disease.