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• W2170836611 abstract "Background Somatic mutation in the X-linked phosphatidylinositol glycan class A gene (PIG-A) causes glycosyl phosphatidylinositol anchor deficiency in human patients with paroxysmal nocturnal hemoglobinuria.Design and Methods We produced an animal model of paroxysmal nocturnal hemoglobinuria by conditional Pig-a gene inactivation (Pig-a−/−) in hematopoietic cells; mice carrying two lox sites flanking exon 6 of the Pig-a gene were bred with mice carrying the transgene Cre-recombinase under the human c-fes promoter. We characterized the phenotypic and functional properties of glycosyl phosphatidylinositol-deficient and glycosyl phosphatidylinositol-normal hematopoietic cells from these Pig-a−/− mice using gene expression microarray, flow cytometry, bone marrow transplantation, spectratyping, and immunoblotting.Results In comparison to glycosyl phosphatidylinositol-normal bone marrow cells, glycosyl phosphatidylinositol-deficient bone marrow cells from the same Pig-a−/− animals showed up-regulation of the expression of immune function genes and contained a significantly higher proportion of CD8 T cells. Both characteristics were maintained when glycosyl phosphatidylinositol-deficient cells were transplanted into lethally-irradiated recipients. Glycosyl phosphatidylinositol-deficient T cells were inactive, showed pronounced Vβ5.1/5.2 skewing, had fewer γ-interferon-producing cells after lectin stimulation, and contained fewer CD4+CD25+FoxP3+ regulatory T cells. However, the levels of T-cell receptor signaling proteins from glycosyl phosphatidylinositol-deficient cells were normal relative to glycosyl phosphatidylinositol-normal cells from wild type animals, and cells were capable of inducing target cell apoptosis in vitro.Conclusions Deletion of the Pig-a gene in hematopoietic cells does not cause frank marrow failure but leads to the appearance of clonally-restricted, inactive yet functionally competent CD8 T cells." @default.
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• W2170836611 date "2009-08-13" @default.
• W2170836611 modified "2023-10-12" @default.
• W2170836611 title "Phenotypic and functional characterization of a mouse model of targeted Pig-a deletion in hematopoietic cells" @default.
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• W2170836611 doi "https://doi.org/10.3324/haematol.2009.011650" @default.
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