To produce transgenic mice which express T cell receptors specific for (IRBP).

产生表达特异T细胞受体（IRBP）的转基因小鼠。

• 批准号: 7535963
• 负责人: Jerold G Woodward
• 金额: $ 25.64万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7535963
• 关键词: 5-(6)-carboxyfluorescein diacetate succinimidyl ester; Adoptive Transfer; Antigens; Applications Grants; Area; Autoantigens; Autoimmune Diseases; Autoimmune Process; Autoimmunity; Backcrossings; Biomedical Research; Breeding; Cell physiology; Cells; Cloning; Communities; Development; Diabetes Mellitus; Disease; Disease model; Effector Cell; Epitopes; Experimental Autoimmune Encephalomyelitis; Experimental Models; Exploratory/Developmental Grant; Eye; Failure; Fluorescent Dyes; Fostering; Genes; Goals; Immune; Immune Tolerance; Immune response; Immunization; In Vitro; Knockout Mice; Label; Lead; Length; Mediating; Methods; Microinjections; Microtus; Modeling; Mononuclear; Multiple Sclerosis; Mus; Numbers; Pancreas; Peripheral; Photoreceptors; Polymerase Chain Reaction; Population; Posterior Uveitis; Pre-Clinical Model; Process; Production; Property; Public Health; RIII Mouse; Receptor Gene; Research; Research Personnel; Research Project Grants; Retina; Risk; Role; Site; Source; Specificity; System; T-Cell Receptor; T-Cell Receptor Genes; T-Lymphocyte; Testing; Thymic epithelial cell; Thymus Gland; Tissues; Transfection; Transgenes; Transgenic Mice; Transgenic Organisms; Uveitis; Vision; alpha-beta T-Cell Receptor; autoimmune uveitis; beta Chain Antigen T Cell Receptor; design; in vivo; interstitial retinol-binding protein; intravital microscopy; model development; mouse interstitial retinol-binding protein; mouse model; novel; receptor; receptor expression; research study; success; zygote

DESCRIPTION (provided by applicant): Autoimmune posterior uveitis is a T cell mediated autoimmune disease characterized by mononuclear infiltrate into the retina and irreversible photoreceptor destruction. While the cause is unknown, experimental autoimmune uveitis (EAU) can be induced in mice through immunization with interphotoreceptor retinoid binding protein (IRBP). Numerous studies in the EAU field as well as other autoimmune disease models suggest that the primary cause of autoimmune disease is a failure of immune tolerance mechanisms. T cell receptor (TCR) transgenic mice have provided, and continue to provide, a wealth of important information on mechanisms of tolerance induction as well as mechanisms of autoimmune tissue destruction, particularly in the multiple sclerosis and diabetes fields. In this exploratory/developmental research grant application, the applicant proposes to develop TCR transgenic mice with specificity for IRBP as a new model for EAU. The applicant has successfully cloned full length cDNAs encoding the alpha and beta chains of the TCR from three IRBP specific T cell clones, and is in the process of cloning the receptor genes from two other T cell clones. In the first aim, the applicant will generate two lines of transgenic mice from two different T cell clones. In the second aim, the applicant will perform the initial characterization of the lines in order to establish them as useful models for EAU. These mice will be made available to the uveitis research community and create valuable new models for uveitis research. Studies using these mice may lead to new therapies for the treatment of uveitis. PUBLIC HEALTH RELEVANCE: This project will generate new transgenic mouse models for autoimmune uveitis, a severe sight threatening autoimmune disease. Similar mouse models have been produced for multiple sclerosis and diabetes and have been responsible for dramatic advances in those fields. These mice will be made available to the research community and thus foster new research into cures or treatment for autoimmune uveitis.

描述（由申请人提供）：自身免疫后葡萄膜炎是一种T细胞介导的自身免疫性疾病，其特征是单核浸润到视网膜和不可逆的光感受器破坏中。虽然原因尚不清楚，但可以通过用球类球类药物结合蛋白（IRBP）免疫来诱导小鼠的实验自身免疫性葡萄膜炎（EAU）。在EAU领域以及其他自身免疫性疾病模型中进行了大量研究表明，自身免疫性疾病的主要原因是免疫耐受机制的失败。 T细胞受体（TCR）转基因小鼠已经提供并继续提供有关耐受性诱导机制以及自身免疫组织破坏机制的大量重要信息，尤其是在多发性硬化症和糖尿病领域。在此探索性/发展研究赠款的应用中，申请人建议开发具有IRBP特异性的TCR转基因小鼠，作为EAU的新模型。申请人已成功克隆了从三个IRBP特异性T细胞克隆的TCR编码TCR的α和β链的全长cDNA，并且正在从其他两个T细胞克隆中克隆受体基因。在第一个目标中，申请人将从两个不同的T细胞克隆中生成两条转基因小鼠。在第二个目标中，申请人将执行线条的初始表征，以便将其确定为EAU的有用模型。这些小鼠将提供给葡萄膜炎研究界，并为葡萄膜炎研究创建有价值的新模型。使用这些小鼠的研究可能会导致用于治疗葡萄膜炎的新疗法。 公共卫生相关性：该项目将生成新的转基因小鼠模型，用于自身免疫性葡萄膜炎，这是一种严重的视力威胁自身免疫性疾病。已经为多发性硬化症和糖尿病产生了类似的小鼠模型，并导致了这些领域的急剧进步。这些小鼠将提供给研究界，从而促进对自身免疫性葡萄膜炎治疗或治疗的新研究。