X-linked chronic granulomatous disease: correction of NADPH oxidase defect by retrovirus-mediated expression of gp91-phox. NLM AIDSLINE Important note: Information in this article was accurate in 1994. The state of the art may have changed since the publication date.

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X-linked chronic granulomatous disease: correction of NADPH oxidase defect by retrovirus-mediated expression of gp91-phox.

Blood. 1993 Oct 1;82(7):2196-202. Unique Identifier : AIDSLINE MED/94003274
Porter CD; Parkar MH; Levinsky RJ; Collins MK; Kinnon C; Division of Cell and Molecular Biology, Institute of Child; Health, London, United Kingdom.

Abstract: Chronic granulomatous disease (CGD) is an inherited immunodeficiency resulting from the inability of an individual's phagocytes to produce superoxide anions because of defective NADPH oxidase. The disease may be treated by bone marrow transplantation and as such is a candidate for somatic gene therapy. Two thirds of patients have defects in an X-linked gene (X-CGD) encoding gp91-phox, the large subunit of the membrane cytochrome b-245 component of NADPH oxidase. Epstein-Barr virus-transformed B-cell lines from patients with CGD provide a model system for the disease. We have used retrovirus-mediated expression of gp91-phox to reconstitute functionally NADPH oxidase activity in B-cell lines from three unrelated patients with X-CGD. The protein is glycosylated and membrane associated, and the reconstituted oxidase is appropriately activated via protein kinase C. The kinetics of superoxide production by such reconstituted cells is similar to that of normal B-cell lines. These data show the potential of gene therapy for this disease.
Keywords: B-Lymphocytes Base Sequence Cell Line Chemiluminescence Cytochrome b/BIOSYNTHESIS/*GENETICS DNA Primers Erythrocytes/ENZYMOLOGY Gene Transfer Granulomatous Disease, Chronic/BLOOD/*ENZYMOLOGY/*GENETICS Hela Cells Herpesvirus 4, Human/GENETICS Human Kinetics Macromolecular Systems Membrane Glycoproteins/ANALYSIS/BIOSYNTHESIS/*GENETICS Molecular Sequence Data Neutrophils/ENZYMOLOGY NADH, NADPH Oxidoreductases/*GENETICS Polymerase Chain Reaction Polyomavirus macacae/GENETICS Retroviridae Superoxides/METABOLISM Support, Non-U.S. Gov't Tetradecanoylphorbol Acetate/PHARMACOLOGY Transduction, Genetic TATA Box *X Chromosome JOURNAL ARTICLEKWDb-lymphocytesbasesequencecelllinechemiluminescencecytochromeb/biosynthesis/KWDgeneticsdnaprimerserythrocytes/enzymologygenetransfergranulomatousdisease,chronic/blood/KWDenzymology/KWDgeneticshelacellsherpesvirus4,human/geneticshumankineticsmacromolecularsystemsmembraneglycoproteins/analysis/biosynthesis/KWDgeneticsmolecularsequencedataneutrophils/enzymologynadh,nadphoxidoreductases/KWDgeneticspolymerasechainreactionpolyomavirusmacacae/geneticsretroviridaesuperoxides/metabolismsupport,non-uKWDsKWDgov'ttetradecanoylphorbolacetate/pharmacologytransduction,genetictataboxKWDxchromosomejournalarticle
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M9410682

Copyright © 1994 - National Library of Medicine. Reproduced under license with the National Library of Medicine, Bethesda, MD.

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