title: The p47phox mouse knock-out model of chronic granulomatous disease.
abstract: Chronic granulomatous disease (CGD) is caused by a congenital defect in phagocyte reduced nicotinamide dinucleotide phosphate (NADPH) oxidase production of superoxide and related species. It is characterized by recurrent life-threatening bacterial and fungal infections and tissue granuloma formation. We have created a mouse model of CGD by targeted disruption of p47phox, one of the genes in which mutations cause human CGD. Identical to the case in human CGD, leukocytes from p47phox-/- mice produced no superoxide and killed staphylococci ineffectively. p47phox-/- mice developed lethal infections and granulomatous inflammation similar to those encountered in human CGD patients. This model mirrors human CGD and confirms a critical role for the phagocyte NADPH oxidase in mammalian host defense.
authors.affiliation: Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-1886, USA.
authors.forename: S H
authors.initials: SH
authors.lastname: Jackson
authors.forename: J I
authors.initials: JI
authors.lastname: Gallin
authors.forename: S M
authors.initials: SM
authors.lastname: Holland
mesh_terms: D000038:Abscess / Q000209:etiology; D000818:Animals; D001424:Bacterial Infections / Q000276:immunology; D001483:Base Sequence; D004198:Disease Susceptibility; D004789:Enzyme Activation; D005260:Female; D006099:Granuloma / Q000209:etiology; D006105:Granulomatous Disease, Chronic / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009181:Mycoses / Q000276:immunology; D009247:NADH, NADPH Oxidoreductases / Q000737:chemistry / Q000172:deficiency* / Q000378:metabolism; D009252:NADPH Dehydrogenase / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D019255:NADPH Oxidases; D010586:Phagocytes / Q000201:enzymology*; D010587:Phagocytosis; D010750:Phosphoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D016897:Respiratory Burst; D013481:Superoxides / Q000378:metabolism
chemical_list: D010750:Phosphoproteins; D017382:Reactive Oxygen Species; D013481:Superoxides; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D009252:NADPH Dehydrogenase