INTACT AND SCID MOUSE MODELS FOR GRAVES' DISEASE

格雷夫斯病的完整和 SCID 小鼠模型

• 批准号: 6380720
• 负责人: TERRY Francis DAVIES
• 金额: $ 28.45万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-01-01 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6380720
• 关键词: Graves disease; SCID mouse; antireceptor antibody; autoantibody; autoimmunity; cell transplantation; clinical research; disease /disorder model; endocrine transplantation; genetically modified animals; hormone receptor; human tissue; hyperthyroidism; immunization; laboratory mouse; model design /development; monoclonal antibody; thyrotropin; tumor infiltrating lymphocyte

DESCRIPTION: (Adapted from the applicant's abstract) This is a competing renewal application, seeking support to continue work with models of murine Graves' disease. Two murine models will be explored: 1) A homologous TSHR immunization model. This version of the Shimojo model uses, instead of immunization with hTSHR-transfected fibroblasts, a homologous system of cell surface-expressed mouse TSHR. 2) A transgenic approach to a Graves' disease model. This model involves the scid/scid transgenic mouse expressing human rather than murine TSHR antigen. These scid-hTSHR mice will be injected with intrathyroidal lymphocytes and engrafted with thyroid tissue from patients with Graves' disease, allowing the human TSHR-Abs to interact with the transgenic human TSHR and induce thyroid overactivity. The applicant believes that the development of both an intact mouse model for Graves' disease as well as the reproduction of the human disease in scid mice will allow a series of interventional procedures to be developed to further the understanding of autoimmune thyroid disease and will provide potential therapeutic approaches to human ATD.

描述：（改编自申请人的摘要）这是一个竞争性的 更新申请，寻求支持以继续研究小鼠模型 格雷夫斯病。将探索两种小鼠模型： 1）同源TSHR免疫模型。此版本的 Shimojo 模型 使用同源物代替 hTSHR 转染的成纤维细胞的免疫 细胞表面表达的小鼠 TSHR 系统。 2) 格雷夫斯病模型的转基因方法。该模型涉及 scid/scid 转基因小鼠表达人类而非小鼠 TSHR 抗原。 这些 scid-hTSHR 小鼠将被注射甲状腺内淋巴细胞并 移植了格雷夫斯病患者的甲状腺组织， 人 TSHR-Abs 与转基因人 TSHR 相互作用并诱导甲状腺 过度活跃。 申请人认为，开发完整的小鼠模型 格雷夫斯病以及人类疾病在 scid 小鼠中的繁殖 将允许开发一系列干预程序以进一步 了解自身免疫性甲状腺疾病并将提供潜力 人类 ATD 的治疗方法。