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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Zhen, L. et al.

Gene targeting of X chromosome-linked chronic granulomatous disease locus in a human myeloid leukemia cell line and rescue by expression of recombinant gp91phox.

The X chromosome-linked chronic granulomatous disease (X-CGD) locus, which encodes the gp91phox subunit of the phagocyte respiratory-burst oxidase cytochrome b, was disrupted by homologous recombination in the PLB-985 human myeloid cell line to develop an in vitro model of X-CGD. Superoxide formation was absent in targeted cells after differentiation to granulocytes but was rescued by stable transfection and expression of wild-type gp91phox cDNA. The targeted cell line should be useful in experiments aimed at defining functional regions within gp91phox by expression of mutant gp91phox cDNAs, complementing studies of naturally occurring mutations in X-CGD. In addition, the mutant line provides a model system in which to establish an experimental basis for the treatment of X-CGD patients with gene replacement therapy. Rescued clones containing even modest amounts of recombinant gp91phox had respiratory-burst activity comparable to the wild-type PLB-985 line, suggesting that functional correction of X-CGD neutrophils may not require high-level expression of gp91phox.[1]

References

Gene targeting of X chromosome-linked chronic granulomatous disease locus in a human myeloid leukemia cell line and rescue by expression of recombinant gp91phox. Zhen, L., King, A.A., Xiao, Y., Chanock, S.J., Orkin, S.H., Dinauer, M.C. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]

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