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.
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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.)
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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
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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)
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