A transgenic model of Gcaves disease bearing human autoantibody genes

携带人类自身抗体基因的 Gcaves 病转基因模型

• 批准号: 14370326
• 负责人: AKAMIZU Takashi
• 金额: $ 8.96万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370326/
• 关键词: Grave's disease; Autoimmune thyroid disease; Transgenic mouse; TSH receptor; トランスジェニックマウル; TSHレセプター抗体

Graves' disease (GD) is. an organ-specific autoimmune disease characterized by hyperthyroidism. Agonistic anti-thyrotropin receptor antibodies (Thyroid-stimulating ([TS]-Ab), which mimic the TSH action, are thought to cause GD. The precise immunological mechanism of TSAb production, however, remains elusive. Previous immunization approaches using TSH receptor led to transient hyperthyroidism, but did not seem sufficient for comprehensive understanding, of the development of autoimmune responses. To create GD-related autoimmunity in mice, we here generated TSAb-transgenic mice in which a patient-derived TSAb is expressed in B cells. Expression of the human TSAb in the mice resulted in various manifestations of hyperthyroidism including increased free thyroxine levels with concomitantly decreased TSH levels, increased thyroid uptake of technetium-pertechnetate, hyperthermia and thyroid hyperplasia. We found a correlation between the serum levels of human TSAb immunoglobulin and free thyroxine. In addition, conventional B cells expressing the TSAb were partially deleted in the, periphery while B 1 cells expressing the TSAb persisted and accumulated in the peritoneal cavity, a finding consistent with previous, demonstrations that the maintenance of B 1 cells plays an important role in the development of autoimmune diseases. Thus, our transgenic mouse may provide a novel and useful animal model for elucidating the pathogenesis and pathophysiology of GD.

坟墓疾病（GD）是。一种特异性的自身免疫性疾病，其特征是甲状腺功能亢进。激动剂抗硫代蛋白受体抗体（甲状腺刺激（[[TS] -Ab）模仿TSH作用）被认为会导致GD。但是，TSAB生产的精确免疫学机制仍然难以捉摸。先前使用TSH受体的免疫能力不足以自动反应，从而有足够的自动化来理解，从而有足够的反应来理解。与GD相关的自身免疫，我们在这里产生了TSAB-转基因小鼠，其中患者衍生的TSAB在B细胞中表达。甲状腺增生性。自身免疫性疾病。因此，我们的转基因小鼠可以提供一种新颖而有用的动物模型来阐明GD的发病机理和病理生理。

项目成果

Akamizu T, Ozaki S, Hiratani H, Uesugi H, Sobajima J, Hataya Y, Kanamoto N, Saijo M, Hattori Y, Moriyama K, Ohmori K, Nakao K: "Drug-induced neutropenia associated with anti-neutrophil cytoplasmic antibodies (ANCA): possible involvement of complement in g

Akamizu T、Ozaki S、Hiratani H、Uesugi H、Sobajima J、Hataya Y、Kanamoto N、Saijo M、Hattori Y、Moriyama K、Ohmori K、Nakao K：“与抗中性粒细胞胞质抗体相关的药物诱导的中性粒细胞减少症（ANCA）

赤水 尚史: "モデル動物作製によるバセドウ病発症機序の解明"J.Clin.Immunol. 26・6. 329-335 (2003)

Naofumi Sekisui：“通过创建模型动物阐明格雷夫斯病的发病机制”J.Clin.Immunol. 26・6 (2003)。

Akamizu T: "Drug-induced neutropenia associated with anti-nrutrophil cytoplasmic antibodies (ANCA) : possible involvement of complement in granulocyte cytotoxicity"Clin Exp Immunol. 127・1. 92-98 (2002)

Akamizu T：“与抗核粒细胞胞质抗体（ANCA）相关的药物诱导的中性粒细胞减少症：补体可能参与粒细胞细胞毒性”Clin Exp Immunol.127·1（2002）。

Akamizu T: "Central effects of ghrelin and growth hormone secretagogue. Pituitary and Periphery : Communication and out"Ed CJ strasburger. 3-15 (2003)

Akamizu T：“生长素释放肽和生长激素促分泌素的中枢作用。垂体和外周：沟通和交流”Ed CJ 斯特拉斯伯格。

Moriyama K: "Thyroid hormone action is disrupted by bidphenol A as an antagonist"J Clin Endorinol Metab. 87・11. 5185-5190 (2002)

Moriyama K：“双酚 A 作为拮抗剂会破坏甲状腺激素的作用”J Clin Endorinol Metab. 87・11 (2002)。