TRANSGENIC ANIMAL MODELS OF HUMAN IMMUNE DEFECTS

人类免疫缺陷的转基因动物模型

• 批准号: 6099002
• 负责人: Steven M Holland
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6099002
• 关键词: NAD(P)H dehydrogenase; child (0-11); chronic granulomatous disease; enzyme activity; gene therapy; genetically modified animals; human subject; human tissue; immunity; interferon gamma; laboratory mouse; model design /development; nonhuman therapy evaluation; recombinant DNA

This project is aimed at understanding the role of enzyme systems in host immune defense, specifically the NADPH oxidase. We are interested in understanding the role of the NADPH oxidase in the generation and control of inflammation and its role in protection from infection. This work will be informative on how to manipulate the host immune system pharmacologically, immunologically, and genetically. We have used a mouse created in my laboratory that is deficient in the NADPH oxidase that closely mimics NADPH oxidase deficiency in humans, chronic granulomatous disease (CGD). In addition to our work on the NADPH oxidase, we are pursuing the underlying basis of another host defense defect, hyper-IgE and recurrent infection syndrome (Job syndrome or HIERIS). This is an autosomal dominant disease characterized by extremely elevated IgE, recurrent sino-pulmonary infections, osteopenia, kyphoscoliosis, pulmonary cysts, and dental abnormalities. Identification of the gene(s) involved will be critically important to our understanding of innate immunity, the host immune response, skeletal growth and development, and dental exfoliation. Once appropriate candidate genes are identified, they will be disrupted in mice and further studies will be carried out.

该项目旨在了解 宿主免疫防御中的酶系统，特别是NADPH 氧化酶。我们有兴趣了解NADPH的作用 氧化酶在炎症的产生和控制中及其在 保护免受感染。这项工作将为如何提供信息 通过药理学操纵宿主免疫系统， 免疫学和遗传学。我们使用了创建的鼠标 我的实验室在NADPH氧化酶中不足 模仿人类的NADPH氧化酶缺乏症，慢性 肉芽肿性疾病（CGD）。除了我们在 NADPH氧化酶，我们正在追求另一个的基础 宿主防御缺陷，超级IGE和复发性感染综合征 （工作综合症或Hieris）。这是一种常染色体显性疾病 以极高升高的IgE，反复发作的中肺特征 感染，骨质减少症，脑感觉，肺囊肿和牙齿 异常。涉及的基因的识别将是批判性的 对我们对先天免疫的理解至关重要 免疫反应，骨骼生长和发育以及牙齿 去角质。一旦确定了适当的候选基因，他们就会 将在小鼠中破坏，并将进行进一步的研究。