Impact of Fli-1 transcription factor on autoantibody and lupus nephritis in NZM2410 mice

Clin Exp Immunol. 2010 Nov;162(2):362-71. doi: 10.1111/j.1365-2249.2010.04245.x. Epub 2010 Aug 20.


The transcription factor Fli-1 is implicated in the pathogenesis of both murine and human lupus. Increased levels of Fli-1 mRNA were present in the peripheral blood lymphocytes from lupus patients; furthermore, transgenic overexpression of Fli-1 in normal mice resulted in the development of a lupus-like disease. Lupus nephritis is a major cause of death in both lupus patients as well as in animal models. In this study, we generated Fli-1 heterozygous knockout (Fli-1(+/)⁻ ) NZM2410 mice (of which the wild-type is a widely used lupus murine model) that expressed decreased levels of Fli-1 and investigated the impact of Fli-1 expression on lupus nephritis development and survival. Ninety-three per cent of the Fli-1(+/)⁻ NZM2410 mice survived to the age of 52 weeks compared to only 35% of wild-type NZM2410 mice. Autoantibodies, including anti-dsDNA and anti-glomerular basement antigen, in Fli-1(+/)⁻ NZM2410 mice were statistically significantly lower when compared to wild-type NZM2410 mice at the ages of 30 and 34 weeks. Total B cell and activated B cell populations in the spleens from Fli-1(+/)⁻ NZM2410 mice were decreased significantly compared to wild-type NZM2410 mice. Fli-1(+/)⁻ NZM2410 mice also had remarkably diminished proteinuria and decreased renal pathological scores when compared with wild-type NZM2410 mice. Expression of early growth response 1 (Egr-1) was decreased significantly in the kidneys from Fli-1(+/)⁻ NZM2410 mice when compared to wild-type littermates. Our data indicate that expression of Fli-1 plays an important role in lupus disease development in NZM2410 mice.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antibodies, Antinuclear / blood
  • Antibody Formation / genetics*
  • Antibody Formation / immunology
  • Autoantibodies / blood*
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology
  • Cell Count
  • Early Growth Response Protein 1 / genetics
  • Female
  • Gene Expression / genetics
  • Immunoglobulin G / blood
  • Kidney / metabolism
  • Kidney / pathology
  • Lupus Nephritis / immunology*
  • Lupus Nephritis / metabolism
  • Lupus Nephritis / pathology
  • Lupus Nephritis / urine
  • Male
  • Mice
  • Mice, Inbred MRL lpr
  • Mice, Knockout
  • Proteinuria / urine
  • Proto-Oncogene Protein c-fli-1 / genetics*
  • Spleen / cytology
  • Spleen / immunology
  • Survival Analysis
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology


  • Antibodies, Antinuclear
  • Autoantibodies
  • Early Growth Response Protein 1
  • Egr1 protein, mouse
  • Fli1 protein, mouse
  • Immunoglobulin G
  • Proto-Oncogene Protein c-fli-1
  • antiglomerular basement membrane antibody