Autoimmune glomerulonephritis with spontaneous formation of splenic germinal centers in mice lacking the estrogen receptor alpha gene

Gil Jin Shim, Loránd Levente Kis, Margaret Warner, Jan Åke Gustafsson

Research output: Contribution to journalArticlepeer-review

77 Scopus citations

Abstract

In mice, ovariectomy accelerates the progression of the end-stage renal disease glomerulosclerosis. In women, the incidence of this disease increases after menopause, and estrogen alters its progression. Polymorphisms in the human estrogen receptor α (ERα) gene have been suggested to constitute a genetic predisposition for lupus nephritis. Here we show that by 1 year of age, mice lacking ERα (ERα-/-) but not those lacking ERβ (ERβ-/-) exhibit immune complex-type glomerulonephritis, proteinuria, and destruction of tubular cells with severe infiltration of B lymphocytes in the kidney and the presence of anti-DNA antibodies in serum. No gender difference occurred in the incidence or severity of these symptoms. However, in female but not in male ERα-/- mice there were elevated serum levels of IgG3. Other prominent features of these mice were (i) spontaneous formation of germinal centers in the spleen in the absence of antigen challenge and (ii) infiltration of plasma cells in the kidney and plasmacytosis in the spleen, Immunohistochemistry indicated a selective expression of ERα protein in the germinal centers but not in the follicular mantle zone of murine spleens and human tonsils. Our results indicate that ERα has indispensable functions in the kidney and in germinal centers, and that defective ERα signaling results in glomerulonephritis.

Original languageEnglish (US)
Pages (from-to)1720-1724
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number6
DOIs
StatePublished - Feb 10 2004

Keywords

  • Bone marrow
  • Fidney
  • Plasma cells
  • Plasmacytosis

ASJC Scopus subject areas

  • Genetics
  • General

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