Strain Distribution Pattern of Susceptibility to Immune-Mediated Nephritis

The genetic basis of immune-mediated nephritis is poorly understood. Recent studies have demonstrated that the NZW mouse strain is more prone to immune-mediated nephritis compared with C57BL/6 and BALB/c strains. The present study extends these findings by challenging 12 additional inbred strains of mice with rabbit anti-mouse glomerular basement membrane (GBM) reactive sera. Compared with control sera-injected mice and anti-GBM-injected A/J, AKR/J, C3H/HeJ, DBA/2J, MRL/MpJ, NOD/LtJ, P/J, SJL/J, and SWR/J mice, the anti-GBM-injected BUB/BnJ, DBA/1J, and 129/svJ mice developed severe proteinuria and azotemia. Their kidneys exhibited pronounced glomerulonephritis, with crescent formation, as well as tubulointerstitial disease, with these phenotypes being particularly profound in 129/svJ mice. However, these strains did not appear to differ in the nature of their xenogeneic immune response to the administered rabbit sera, either quantitatively or qualitatively. Collectively, these findings allude to the presence of genetic elements in the BUB/BnJ, DBA/1J, and 129/svJ genomes that may potentially confer susceptibility to immune-mediated nephritis. Detailed studies to dissect out the immunological and genetic basis of renal disease in these three strains are clearly warranted.