Details

Autor(en) / Beteiligte

• Kimura, J
• Ichii, O
• Nakamura, T
• Horino, T
• Otsuka, S
• Kon, Y

Titel

BXSB-type genome causes murine autoimmune glomerulonephritis: pathological correlation between telomeric region of chromosome 1 and Yaa

Ist Teil von

• Genes and immunity, 2014-04, Vol.15 (3), p.182-189

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2014

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.