Glomerular-specific alterations of VEGF-A expression lead to distinct congenital and acquired renal diseases
J. Clin. Invest. Vera Eremina, et al. 111:707 doi:10.1172/JCI17423 [Go to this article.]

Figure 2
Heterozygous VEGF-loxP^+/–,Neph-Cre^+/– mice develop nephrotic syndrome and end-stage renal failure by 9 weeks of age. (a) SDS-PAGE analysis was performed using 2 μl of mouse urine. Lane 1 contains molecular weight markers, lane 2 shows urine from a VEGF-loxP^–/–,Neph-Cre^+/– control aged 9 weeks, and lane 3 shows urine from a 9-week-old sick VEGF-loxP^+/–,Neph-Cre^+/– animal. The presence of a large amount of albumin measuring 66.2 kDa is identified in the sick mouse and demonstrates damage to the kidney filter. In contrast, low–molecular-weight proteins, which are normally found in mouse urine, are not different. (b) Bar graph showing elevated creatinine (more than ten times higher than normal), elevated urea, and decreased hemoglobin (Hgb) in VEGF-loxP^+/–,Neph-Cre^+/– mice (VEGF-pod^+/–) at 9 weeks of age compared with VEGF-loxP^+/–,Neph-Cre^–/– and VEGF-loxP^–/–,Neph-Cre^+/– mice (combined for analysis and considered as wild type). (c) Whole-mount image of a kidney from a sick 9-week-old VEGF-loxP^+/–,Neph-Cre^+/– (+/–) mouse compared with that of a wild-type littermate (+/+). The affected kidney is pale and shrunken. Magnification: ×60. (d) A wild-type glomerulus. Note the open capillary loops (Cap). ×350. (e) A glomerulus from a heterozygous VEGF-A mouse. All the glomeruli are grossly distorted morphologically. Note the empty cytoplasmic vacuoles (v) that are present in podocytes. No patent capillary loops can be seen. Dilated tubules (t) can be seen and in most places are packed with proteinaceous material, consistent with nephrotic syndrome. Magnification: ×375.