Disease phenotype in FH W1206R mutant mice is mediated by AP complement. (A) FH^R/R mice with C3 or FD deficiency survived normally, whereas their FH^R/R littermates with normal C3 and FD had high mortality (FH^R/RC3^−/− n = 64, FH^R/RC3^+/+ n = 38, FH^R/RFD^−/− n = 60, and FH^R/RFD^+/+ n = 36). (B) BUN of FH^R/R mice (n = 10) was significantly increased between 5 and 10 weeks of age, whereas BUN in FH^R/RC3^−/− (n = 6) and FH^R/RFD^−/− (n = 7) mice remained the same at 5 and 10 weeks of age. (C) CBC analysis showed that FH^R/RC3^−/− (n = 9) and FH^R/RFD^−/− (n = 9) mice had normal blood platelet counts and Hb levels, whereas their FH^R/R littermates (n = 13) had thrombocytopenia and anemia compared with FH^W/W mice (n = 13). (D) Representative pictures of kidney (PAS staining) and liver (hematoxylin and eosin staining) histology, retinal funduscopy, and fluorescence angiography showing that there was no glomerular injury in the kidney or thrombosis in the liver and eye of FH^R/RC3^−/− and FH^R/RFD^−/− mice and no retinopathy. Scale bars in panel D represent 25 μm (kidney), 50 μm (liver), and 200 μm (eye). Data in panel B represent mean ± SD. Horizontal bars across scatterplots in panel C represent average values. *P < .05; **P < .01; and ***P < .001 (Mantel-Haenszel log-rank test for panel A; 1-way ANOVA and Student t test for other panels).