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

Abstract

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.

• Authors: J Mathenia, E Reyes-Cortes, S Williams, I Molano, P Ruiz, D K Watson, G S Gilkeson, X K Zhang
• Journal: Clinical and experimental immunology (Clin Exp Immunol) Vol. 162 Issue 2 Pg. 362-71 (Nov 2010) ISSN: 1365-2249 [Electronic] England
• PMID: 20731671 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: © 2010 British Society for Immunology.

Chemical References

• 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

Topics

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