Fig 1: delFH-FHR mice coexpressing hFH and FHR5mut recapitulate CFHR5 nephropathy. (A) Schematic showing the generation of the hFH-FHR5 and hFH-FHR5mut strains. The transgenic cassette contained each cDNA in tandem, separated by an IRES, under the control of a loxP-dependent cytomegalovirus early enhancer/chicken β-actin promoter (pCAG). (B) Plasma hFH and (C) FHR5 levels. Bars denote the mean, and whiskers denote the SD. P values are derived from ANOVA with Bonferroni multiple comparisons test. (D) Western blot of FHR5 demonstrating the expression of WT and mutant FHR5 protein. Normal mouse sera (NMS), normal human sera (NHS), and FHR5 nephropathy serum (R5M) are shown. (E) Plasma C3 levels by ELISA. Bars denote the mean, and whiskers denote the SD. P values are derived from ANOVA with Bonferroni multiple comparisons test. (F) Representative glomerular immunostaining images of C3b/iC3b/C3c, C3d, FHR5/FHR5mut, FH, IgG, and properdin in 3-mo-old mice. (G) Representative glomerular images from Periodic acid–Schiff–stained renal sections from 12-mo-old mice. hFH-FHR5mut male mice show conspicuous capillary wall thickening (arrows). Scoring of capillary wall double contours in 12-mo-old mice. Bars denote the median, and whiskers denote the interquartile range. ****P < 0.0001; P values are derived from Kruskal–Wallis test with Dunn’s multiple comparisons test. (H) Representative glomerular electron microscopy images from hFH-FHR5 and hFH-FHR5mut 12-mo-old male mice. Male hFH-FHR5mut show large subendothelial electron-dense deposits (asterisks) and multiple electron-dense deposits in the mesangium (m). Smaller subendothelial deposits are seen in female hFH-FHR5mut animals. The hFH-FHR5 mice show no abnormalities apart from occasional small mesangial deposits (arrow).