Mouse model of X–linked chronic granulomatous disease, an inherited defect in phagocyte superoxide production

Gene targeting was used to generate mice with a null allele of the gene involved in X–linked CGD, which encodes the 91 kD subunit of the oxidase cytochrome b, and affected hemizygous male mice lacked phagocyte superoxide production and had an altered inflammatory response in thioglycollate peritonitis.

Abstract

Chronic granulomatous disease (CGD) is a recessive disorder characterized by a defective phagocyte respiratory burst oxidase, life-threatening pyogenic infections and inflammatory granulomas. Gene targeting was used to generate mice with a null allele of the gene involved in X-linked CGD, which encodes the 91 kD subunit of the oxidase cytochrome b. Affected hemizygous male mice lacked phagocyte superoxide production, manifested an increased susceptibility to infection with Staphylococcus aureus and Aspergillus fumigatus and had an altered inflammatory response in thioglycollate peritonitis. This animal model should aid in developing new treatments for CGD and in evaluating the role of phagocyte-derived oxidants in inflammation.