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Onset of autoimmune glomerulonephritis derived from the telomeric region of MRL-chromosome 1 is associated with the male sex hormone in mice

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

A Konno

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

N Sasaki

Laboratory of Experimental Animal Science, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan

D Endoh

Department of Veterinary Radiology, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido, Japan

Y Hashimoto

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

Y Kon

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

Female B6.MRLc1(82–100) congenic mice develop more severe autoimmune glomerulonephritis (AGN) than males. We assessed the effects of gonadectomy on the pathogenesis of AGN in these mice. One-month-old male and female mice were divided into sham-operated group (SG) and gonadectomized group (GG), and the pathological changes were investigated at 8 months. SG females showed higher spleen and thymus weights, serum total IgG and autoantibody levels, glomerular damage scores and percent IgG- and CD3-positive glomeruli as compared with SG males. Gonadectomy showed more remarkable effects in males than in females. Spleen and thymus weights, urinary albumin excretion, glomerular damage scores, percent IgG- and CD3-positive glomeruli, and CD3-positive areas in the spleen were significantly higher in GG males than in SG males. CD3-positive cells were observed in both the thymic cortex and medulla in all animals except SG males. The expression ratio of active Fc gamma receptor (Fcgr) 3 to inhibitory Fcgr2b in the kidneys, which we have previously demonstrated to have a great impact on pathogenesis in B6.MRLc1(82–100), was significantly higher in GG males than in SG males. These results suggested that the differences in the pathogenesis of AGN are primarily because of the inhibitory roles of the male sex hormones.

Key Words: autoimmune glomerulonephritis • gonadectomy • kidney • MRL mouse • sex differences

Lupus, Vol. 18, No. 6, 491-500 (2009)
DOI: 10.1177/0961203308098989


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