Transgenic Animal Models Of Human Immune Defects

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Abstract

We seek to understand the role of enzyme systems in host immune defense, specifically the NADPH oxidase. We study the NADPH oxidase in the generation and control of inflammation and its role in protection from infection. This is important to understand how to manipulate the 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 the disease caused by NADPH oxidase deficiency in humans, chronic granulomatous disease (CGD). We also follow a large number of patients with CGD, and thus are able to examine the same features in animal models and the human disease. We are also pursuing the genetic and cellular basis of another host defense defect, hyper-IgE and recurrent infection syndrome (Job syndrome or HIE), an autosomal dominant disease characterized by extremely elevated IgE, recurrent sino- pulmonary infections, osteopenia, kyphoscoliosis, pulmonary cysts, and dental abnormalities. 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. Appropriate candidate genes will be disrupted in mice and functional studies will be performed.