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. 2011 May;31(10):2162–2170. doi: 10.1128/MCB.05234-11

Fig. 4.

Fig. 4.

Podocyte-specific KO mice are predisposed to doxorubicin hydrochloride-induced nephropathy. KO, knockout mice (Pod::Cre/+; Myh9f/f); ff, control mice (+; Myh9f/f); PCre, control mice (PCre; +/+); Adr, doxorubicin hydrochloride (Adriamycin) in saline; Sal, saline only. (A) Coomassie blue-stained SDS-PAGE gel with urines 2 weeks after injection of saline or doxorubicin hydrochloride. An albumin standard is shown at 5-fold dilutions, with the arrow indicating albumin. All urines with heavy albuminuria were from KO animals. (B) Urine ELISA albumin/creatinine ratios after injection of mice with saline or doxorubicin hydrochloride (means ± standard errors of the means). Doxorubicin hydrochloride-treated KO mice had more albuminuria than all other groups at weeks 3, 4, and 6 (Welsch's t test [unpaired, not assuming equal variances, and one-tailed]). All pairwise combinations with doxorubicin hydrochloride-treated KO mice had P values of 0.05 or less, although due to the large standard error of the mean, the significance was borderline for doxorubicin hydrochloride-treated KO versus doxorubicin hydrochloride-treated ff mice at 4 weeks (P value = 0.0524) and for doxorubicin hydrochloride-treated KO versus doxorubicin hydrochloride-treated ff mice at 3 weeks (P value = 0.0526). (C) KO mice develop focal and segmental glomerulosclerosis. Some images were removed to accommodate available space. 1, global sclerosis; 2, segmental sclerosis; arrow, proteinaceous cast. Images for ff control mice and PCre+ mice injected with saline were similar to those for KO mice injected with saline and are not shown. (D) Mean glomerulosclerosis severity scores (± standard deviations), judged blindly, albeit subjectively (1 to 4+), for two mice for each condition. N, total number of glomeruli. Median scores are reported in Results. By the nonparametric Mann-Whitney test, there was no difference between saline-treated groups or between PCre controls treated with doxorubicin hydrochloride versus saline, but there was a significant difference between KO mice treated with doxorubicin hydrochloride and every other group (P < 1e−6).