Nature Genetics
9, 202 - 209 (1995)
doi:10.1038/ng0295-202
Mouse model of X−linked chronic granulomatous disease, an inherited defect in phagocyte superoxide productionJonathan D. Pollock1, David A. Williams1, 2, Mary A.C. Gifford1, Ling Lin Li1, Xunxiang Du1, Jason Fisherman3, Stuart H. Orkin3, 4, Claire M. Doerschuk1
& Mary C. Dinauer1
1Herman B Wells Center for Pediatric Research, Departments of Pediatrics and of Medical and Molecular Genetics, James Whitcomb Riley Hospital for Children, Indiana University Medical Center,
2Howard Hughes Medical Institute, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
3Division of Hematology/Oncology, Children's Hospital and the Dana Farber Cancer Institute, Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115, USA
4Howard Hughes Medical Institute, Boston, Massachusetts 02115, USA Correspondence should be addressed to M.C.D. 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.
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