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2582 Vascular endothelial growth factor receptor (VEGFR)-1 and VEGFR-2, also known as fms-like tyrosine kinase (Flt-1) and fetal liver kinase 1 (Flk-1)/kinase insert domain receptor (KDR) respectively, are receptor tyrosine kinases that bind with high affinities to members of the VEGF family. Although both receptors bind the original member of the family, VEGF-A, they display distinct binding specificities for other VEGFs, as VEGFR-1 also binds placenta growth factor (PlGF) and VEGF-B, whereas VEGFR-2 binds VEGF-C and VEGF-D in addition to VEGF. VEGFR-1 and VEGFR-2 are predominantly expressed on vascular endothelium, but their expression has also been demonstrated on other cell types, most notably cells of the hematopoietic lineages. Targeted disruption of VEGFR-1 and VEGFR-2 expression in mice demonstrates the critical role of these receptors in vascular development. Homozygous null VEGFR-1 mice die at midgestation due to defects in hemangioblast differentiation and consequently impaired vascular formation. VEGFR-2 knockout mice fail to develop significant numbers of hematopoietic precursors and angioblasts and die at E8.5. Although the generation of such conventional knockouts has been critical for our understanding of the role of these receptors during early embryonic development, their early embryonic lethality precludes the study of the role of VEGFR-1 and VEGFR-2 during later stages of embryogenesis, in adult tissues, and during pathological situations. In addition, more recent studies focusing on the role of these receptors in hematopoiesis and endothelial cell progenitor (EPC) recruitment suggest that these receptors have important functions in addition to their role in classical vascular development. The capacity to generate tissue- or time-specific deletions of VEGFR-1 and/or VEGFR-2 would also greatly benefit these relatively new areas of research. To this end, we have generated two lines of mice, denoted VEGFR-1-LOX and VEGFR-2-LOX, in which the first coding exon and a region of the promotor of each gene is flanked by LoxP sites. To generate conditional knockouts of either receptor, mice are bred to strains that express Cre-recombinase driven by inducible (MX1-CRE) or cell-specific promoters (Tie2-CRE), resulting in excision of the DNA sequence intervening the LoxP sites and resulting in a null VEGFR-1 or VEGFR-2 allele at sites of Cre-recombinase expression. VEGFR-1-LOX and VEGFR-2-LOX mice are important tools for in vivo studies that will aid our understanding of the role of these receptors in various physiological processes.