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. 2018 Apr;93(4):903–920. doi: 10.1016/j.kint.2017.11.014

Figure 1.

Figure 1

Temporal induction of glomerulosclerosis in CAGG-CreERTM−/+;Wt1f/ftransgenic mice following tamoxifen induction (a–d). (a) At day (D) 4 postinduction (PI), glomeruli of CAGG-CreERTM−/+;Wt1f/f transgenic mice (mutants) are morphologically similar to their controls, CAGG-CreERTM−/−;Wt1f/f transgenic mice. (See Supplementary Figure S2 for analysis of heterozygous CAGG-CreERTM−/+;Wt1f/+ littermates and Supplementary Figure S3 for analysis of severity of glomerulosclerosis). Bars = 50 μm. (a′) Quantitative graph showing mean urine albumin-creatinine ratio (μg/mg) ±SEM at D4 PI controls versus mutants (n = 14 vs. n = 10); 104.4 ± 25.71 versus 563.5 ± 443, P = 0.21, Student t-test. (b) At D5 PI, mutant mice exhibit segmental glomerulosclerosis compared with control mice (for quantitative analysis, see also Supplementary Figure S3). (b′) Quantitative graph showing mean urine albumin-creatinine ratio (μg/mg) at D5 PI in controls versus mutants (n = 14 vs. n = 14); 217 ± 157.5 versus 11,654 ± 4304, *P = 0.01, Student t-test. (c) At D6 PI, more extensive glomerulosclerosis is evident in mutants compared with control mice with hyaline-filled tubules. (c′) Quantitative graph showing mean urine albumin-creatinine ratio (μg/mg) at D6 PI in controls versus mutants (n = 5 vs. n = 6); 79.8 ± 29.8 versus 15,202 ± 7210, **P = 0.004, Student t-test. (d) By D12 PI, glomeruli of mutant mice exhibit global glomerulosclerosis, hyaline-filled tubules, and pyknotic podocyte nuclei with extensive tubulointerstitial disease (see also Supplementary Figure S5). (d′) Quantitative graph showing mean urine albumin-creatinine ratio (μg/mg) at D12 PI controls versus mutants (n = 7 vs. n = 7); 76.8 ± 13.9 versus 9469 ± 4279, *P = 0.04, Student t-test. (e) Western blot analysis from D4, D5, D6, and D12 PI shows evidence of increased albuminuria in mutant urine during disease progression in CAGG-CreERTM−/+;Wt1f/f transgenic mice compared with Cre-negative control mice. To optimize viewing of this image, please see the online version of this article at www.kidney-international.org.