Whole body deletion of VEGFR-2 results in vascular defects, with glomerular thrombotic microangiopathy. Whole body deletion of VEGFR-2 results in vascular defects, with glomerular thrombotic microangiopathy. (A) Conditional whole body VEGFR-2 knockout mice contain five transgenes. rtTA is expressed by all cells of the body and, with DOX, binds to the tetO-regulated Cre protein. Cre induces recombination between the loxP sites on the VEGFR-2 allele and results in VEGFR-2 deletion in all cells. (B) PCR analysis of tail genomic DNA shows Cre-mediated excision of the floxed VEGFR-2 region (floxed allele, 439 bp; wild-type allele, 322 bp; deleted allele, 218 bp). (C) Light micrographs show pristine glomeruli in control mice (i through iii). Glomeruli from mutant mice show global glomerular damage [(iv through ix); black arrows in (iv)]. Features of chronic TMA include fragmented red blood cells [black arrows in (vi)], interposition of mesangial cells [white arrowhead in (viii)] and marked thickening of the wall of a capillary loop [black arrowhead in (ix)]. Top row and (viii): periodic acid–Schiff stain; (ii and v): hematoxylin and eosin stain. Bottom row: Trichrome masson stain. Original magnifications: ×100 (i and iv); ×400 (ii and v); ×800 (iii, vi, and ix); ×1000 (viii). Karen Sison et al. JASN 2010;21:1691-1701 ©2010 by American Society of Nephrology