The p47phox mouse knock-out model of chronic granulomatous disease.

TLDR

Chronic granulomatous disease results from a congenital defect in phagocyte NADPH oxidase that impairs superoxide production, leading to recurrent life‑threatening bacterial and fungal infections and granuloma formation. We generated a CGD mouse model by disrupting the p47phox gene, a key component of the NADPH oxidase complex. p47phox‑/‑ mice exhibit absent superoxide production, ineffective staphylococcal killing, lethal infections, and granulomatous inflammation that closely recapitulate human CGD, confirming the essential role of phagocyte NADPH oxidase in host defense.

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.