FIGURE 7:

Podocyte IRE1α deletion increases susceptibility to acute anti-GBM nephritis. (A) Male mice 5 mo of age were injected with 5 μl of sheep anti–GBM antibody (αGBM). Urine was collected preinjection and at 24 h. Kidneys were harvested at 24 h. In mice that received anti-GBM antibody, there was significantly greater albuminuria in the IRE1α^{flox/flox;Cre} (M Cre) group than in controls (IRE1α^flox/flox;+; M +). Albuminuria in anti-GBM M Cre mice was also significantly greater than the preinjection (baseline) value (*p = 0.005, ANOVA; N, number of animals). (B) The net change in albumin/creatinine ratio calculated per individual mouse for 10 anti-GBM injected M Cre mice and 6 injected M + mice was significantly greater in M Cre mice (*p = 0.049). (C–F) Anti-GBM antibody and C3 deposition in mouse glomeruli were confirmed by immunofluorescence microscopy. Quantification of sheep anti-GBM fluorescence intensity showed a slight increase in M Cre mice (*p = 4.27 × 10⁻⁷; 83 glomeruli from six GBM-injected M + mice and 110 glomeruli from seven GBM-injected M Cre mice). There were no significant differences in C3 deposition. C3 fluorescence intensity was measured in 80 glomeruli from six M + mice and 98 glomeruli from seven M Cre mice. Scale bars, 50 μm.