Abstract |
The autoimmune-prone BXSB/MpJ-Yaa mouse is a model of membranous proliferative glomerulonephritis (MPGN). Severe MPGN has been reported only in male BXSB/MpJ-Yaa mice because of the Y-linked autoimmune accelerator (Yaa) locus. However, we show that female BXSB/MpJ mice develop age-related MPGN without Yaa. Female BXSB/MpJ mice clearly developed MPGN characterized by increased mesangial cells, thickening of the glomerular basement membrane (GBM), double contouring and spike formation of GBM with T-cell infiltrations and podocyte injuries corresponding with increased autoantibody production and albuminuria. Analysis of the renal levels of the Fc gamma receptor (Fcgr) and interferon-activated gene 200 (Ifi200) family genes, which are MPGN candidate genes localized to the telomeric region of chromosome 1 (Chr.1), showed that Fcgr2b levels decreased, whereas Fcgr3 and Ifi202b levels increased in female BXSB/MpJ mice compared with healthy C57BL/6 mice. Furthermore, in isolated glomeruli, microarray analysis revealed that Fcgr3, Fcgr4 and Ifi202b expression was higher in male BXSB/MpJ-Yaa mice than in male BXSB/MpJ mice. These findings indicate that the BXSB/MpJ-type genome causes age-related MPGN with significant contribution from the telomeric region of Chr.1, and Yaa enhances the expression of genes localizing to this locus, thereby leading to severe MPGN in male mice.
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Authors | J Kimura, O Ichii, T Nakamura, T Horino, S Otsuka, Y Kon |
Journal | Genes and immunity
(Genes Immun)
2014 Apr-May
Vol. 15
Issue 3
Pg. 182-9
ISSN: 1476-5470 [Electronic] England |
PMID | 24477164
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Topics |
- Animals
- Autoimmune Diseases
(genetics, immunology)
- Chromosomes, Mammalian
- Female
- Gene Expression
- Genetic Predisposition to Disease
- Glomerulonephritis
(genetics, immunology, pathology, physiopathology)
- Kidney Function Tests
- Kidney Glomerulus
(immunology, pathology, ultrastructure)
- Male
- Mice
- Mice, Inbred C57BL
- Podocytes
(metabolism, pathology)
- Telomere
- Y Chromosome
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