title: Correction of accelerated autoimmune disease by early replacement of the mutated lpr gene with the normal Fas apoptosis gene in the T cells of transgenic MRL-lpr/lpr mice.
abstract: MRL-lpr/lpr mice develop a generalized autoimmune disease which includes increased autoantibody production, glomerulonephritis, and development of lymphadenopathy. The lpr genetic defect has been identified as a mutation in the Fas apoptosis gene that results in low expression of Fas mRNA. To determine the significance of the lpr mutation and T cells in the development of the autoimmune disease, we constructed transgenic MRL-lpr/lpr mice using a full-length murine Fas cDNA under the regulation of the T-cell-specific CD2 promoter and enhancer. Here we show that the early correction of the lpr gene defect in T cells eliminates glomerulonephritis and development of lymphadenopathy and decreases the levels of autoantibodies. In this model, early correction of the lpr defect in T cells is sufficient to eliminate the acceleration of autoimmune disease even in the presence of B cells and other cells that express the mutant lpr gene.
authors.affiliation: University of Alabama at Birmingham 35294.
authors.forename: J
authors.initials: J
authors.lastname: Wu
authors.forename: T
authors.initials: T
authors.lastname: Zhou
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: J
authors.initials: J
authors.lastname: He
authors.forename: W C
authors.initials: WC
authors.lastname: Gause
authors.forename: J D
authors.initials: JD
authors.lastname: Mountz
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000235:genetics*; D017209:Apoptosis / Q000235:genetics*; D001327:Autoimmune Diseases / Q000235:genetics* / Q000628:therapy; D001483:Base Sequence; D015152:Blotting, Northern; D004247:DNA; D004742:Enhancer Elements, Genetic; D005455:Fluorescent Antibody Technique; D006801:Humans; D008232:Lymphoproliferative Disorders / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009154:Mutation; D011401:Promoter Regions, Genetic; D013601:T-Lymphocytes / Q000166:cytology*; D019014:fas Receptor
chemical_list: D000954:Antigens, Surface; D019014:fas Receptor; D004247:DNA