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

Genes & Immunity volume 15, pages 182–189 (2014)Cite this article

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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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Acknowledgements

This work was supported by a Grants-in-Aid for Scientific Research from Graduate School of Veterinary Medicine, Hokkaido University, a Grant-in-Aid for JSPS Fellows (No. 25000961), a Grant-in-Aid for Young Scientist (No. 24688033) and a Grant-in-Aid for Scientific Research B (No. 24380156) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

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Authors and Affiliations

  1. Department of Biomedical Sciences, Laboratory of Anatomy, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan

    J Kimura, O Ichii, T Nakamura, S Otsuka & Y Kon

  2. Section of Biological Safety Research, Chitose Laboratory, Japan Food Research Laboratories, Chitose, Japan

    T Nakamura

  3. Department of Endocrinology, Metabolism and Nephrology, Kochi Medical School, Kochi University, Nankoku, Japan

    T Horino

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  1. J Kimura
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Correspondence to Y Kon.

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Kimura, J., Ichii, O., Nakamura, T. et al. BXSB-type genome causes murine autoimmune glomerulonephritis: pathological correlation between telomeric region of chromosome 1 and Yaa. Genes Immun 15, 182–189 (2014). https://doi.org/10.1038/gene.2014.4

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