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

Jianguo Wu, Tong Zhou, Jinju Zhang, Jin He, William Gause, John D. Mountz

Research output: Contribution to journalArticle

141 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2344-2348
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number6
DOIs
StatePublished - Mar 15 1994

All Science Journal Classification (ASJC) codes

  • General

Keywords

  • autoimmunity
  • systemic lupus erythematosus

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