BXSB-type genome causes murine autoimmune glomerulonephritis: pathological correlation between telomeric region of chromosome 1 and Yaa.
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.
Laboratory of Anatomy, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
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Kimura
Laboratory of Anatomy, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
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Ichii
1] Laboratory of Anatomy, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan [2] Section of Biological Safety Research, Chitose Laboratory, Japan Food Research Laboratories, Chitose, Japan.
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Nakamura
Department of Endocrinology, Metabolism and Nephrology, Kochi Medical School, Kochi University, Nankoku, Japan.
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Horino
Laboratory of Anatomy, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
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Otsuka
Laboratory of Anatomy, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
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Kon
D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology; D033481:Chromosomes, Mammalian; D005260:Female; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D005921:Glomerulonephritis / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D007677:Kidney Function Tests; D007678:Kidney Glomerulus / Q000276:immunology / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D050199:Podocytes / Q000378:metabolism / Q000473:pathology; D016615:Telomere; D014998:Y Chromosome