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。

基本信息

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
项目类别：
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

项目摘要

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）：自身免疫性后葡萄膜炎是一种 T 细胞介导的自身免疫性疾病，其特征是单核细胞浸润到视网膜和不可逆的光感受器破坏。虽然原因尚不清楚，但通过使用光感受器间视黄醇结合蛋白 (IRBP) 进行免疫接种，可以在小鼠中诱导实验性自身免疫性葡萄膜炎 (EAU)。 EAU 领域以及其他自身免疫性疾病模型的大量研究表明，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）转基因小鼠已经并将继续提供关于耐受诱导机制以及自身免疫组织破坏机制的大量重要信息，特别是在多发性硬化症和糖尿病领域。在这项探索性/发展性研究资助申请中，申请人提议开发具有IRBP特异性的TCR转基因小鼠作为EAU的新模型。申请人已经从三个IRBP特异性T细胞克隆中成功克隆了编码TCR的α和β链的全长cDNA，并且正在从另外两个T细胞克隆中克隆受体基因。第一个目标是，申请人将从两个不同的 T 细胞克隆中产生两个转基因小鼠品系。在第二个目标中，申请人将对生产线进行初步表征，以便将它们建立为 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带来治疗葡萄膜炎的新疗法。公共健康相关性：该项目将为自身免疫性葡萄膜炎（一种严重威胁视力的自身免疫性疾病）产生新的转基因小鼠模型。类似的小鼠模型已经针对多发性硬化症和糖尿病产生，并为这些领域的巨大进步做出了贡献。这些小鼠将提供给研究界，从而促进自身免疫性葡萄膜炎的治愈或治疗的新研究。