This project is directed at understanding the role of specific enzyme systems in generating and maintaining host immunity. The approach taken involves the creation of mice with discrete defects in host defenses by using homologous recombination of DNA into the host genome to disrupt relevant genes. Lesions have been introduced that correspond to previously identified mutations in humans that incapacitate important host defense systems. This project relies upon a thorough understanding of the molecular and functional organization of the NADPH oxidase system and the mutations which disable it. Further, the dissection of specific phenotypes associated with the defined genotypes may provide insight into the importance of certain functional domains of the genes of the NADPH oxidase and indicate which sites are most informative for further study. We have used the NADPH oxidase system as a paradigm for the creation of mice with a genetic defect similar to one found in humans, chronic granulomatous disease (CGD). Using homologous recombination, we have created mice by which are deficient in the p47phox gene product, a necessary component of the NADPH oxidase complex.
| Falcone, E Liana; Petts, Jennifer R; Fasano, Mary Beth et al. (2016) Methylotroph Infections and Chronic Granulomatous Disease. Emerg Infect Dis 22:404-9 |
| Hsu, Amy P; Sowerwine, Kathryn J; Lawrence, Monica G et al. (2013) Intermediate phenotypes in patients with autosomal dominant hyper-IgE syndrome caused by somatic mosaicism. J Allergy Clin Immunol 131:1586-93 |
| Kuhns, Douglas B; Alvord, W Gregory; Heller, Theo et al. (2010) Residual NADPH oxidase and survival in chronic granulomatous disease. N Engl J Med 363:2600-10 |
| Cortes, Lizette M; Mattapallil, Mary J; Silver, Phyllis B et al. (2008) Repertoire analysis and new pathogenic epitopes of IRBP in C57BL/6 (H-2b) and B10.RIII (H-2r) mice. Invest Ophthalmol Vis Sci 49:1946-56 |
| Ling, Jennifer C; Freeman, Alexandra F; Gharib, Ahmed M et al. (2007) Coronary artery aneurysms in patients with hyper IgE recurrent infection syndrome. Clin Immunol 122:255-8 |
| Freeman, Alexandra F; Collura-Burke, Christina J; Patronas, Nicholas J et al. (2007) Brain abnormalities in patients with hyperimmunoglobulin E syndrome. Pediatrics 119:e1121-5 |
| Greenberg, David E; Porcella, Stephen F; Zelazny, Adrian M et al. (2007) Genome sequence analysis of the emerging human pathogenic acetic acid bacterium Granulibacter bethesdensis. J Bacteriol 189:8727-36 |
| Woellner, Cristina; Schaffer, Alejandro A; Puck, Jennifer M et al. (2007) The hyper IgE syndrome and mutations in TYK2. Immunity 26:535;author reply 536 |
| Doerries, Carola; Grote, Karsten; Hilfiker-Kleiner, Denise et al. (2007) Critical role of the NAD(P)H oxidase subunit p47phox for left ventricular remodeling/dysfunction and survival after myocardial infarction. Circ Res 100:894-903 |
| Siddiqui, Sophia; Anderson, Victoria L; Hilligoss, Diane M et al. (2007) Fulminant mulch pneumonitis: an emergency presentation of chronic granulomatous disease. Clin Infect Dis 45:673-81 |
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