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The p47phox mouse knock-out model of chronic granulomatous disease
S H Jackson1, J I Gallin, S M Holland
1Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-1886, USA.
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.
Insights
Researchers developed a mouse model for Chronic Granulomatous Disease (CGD) by disrupting the p47phox gene. This model accurately replicates CGD, confirming the crucial role of phagocyte NADPH oxidase in host defense against infections.
Area of Science:
- Immunology
- Genetics
- Infectious Diseases
Background:
- Chronic Granulomatous Disease (CGD) results from defective phagocyte NADPH oxidase, leading to severe infections.
- Patients experience recurrent bacterial and fungal infections and granuloma formation.
Purpose of the Study:
- To create and validate a mouse model for CGD.
- To confirm the essential role of the phagocyte NADPH oxidase in host defense.
Main Methods:
- Targeted disruption of the p47phox gene in mice.
- Analysis of leukocyte superoxide production and bacterial killing.
- Observation of infection susceptibility and inflammatory responses.
Main Results:
- p47phox-/- mice exhibited no superoxide production by leukocytes.
- These mice showed ineffective killing of staphylococci.
- p47phox-/- mice developed lethal infections and granulomatous inflammation, mirroring human CGD.
Conclusions:
- The p47phox-/- mouse is a valid model for studying human CGD.
- This model confirms the critical role of phagocyte NADPH oxidase in combating infections.
- Findings underscore the importance of this enzyme complex in mammalian host defense.