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• W2562840432 abstract "Proc Amer Assoc Cancer Res, Volume 46, 20056128 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. Conventional gene-targeting strategies demonstrated the essential roles of VEGFR-1 and VEGFR-2 during early embryonic development, as mouse embryos that are null for either receptor die between days 8.5 and 9.5 due to profound defects in angiogenesis and formation of a functional cardiovascular system. However, due to the early embryonic lethality of VEGFR-1 and VEGFR-2 null mice, the role of these receptors during early postnatal life and in the adult has remained unclear. To assess the role of VEGFR-1 and VEGFR-2 in postnatal development, we have utilized the Cre-LoxP system to generate conditional knockouts of either receptor. VEGFR-1-LoxP and VEGFR-2-LoxP mice, in which the first coding exon and a region of the promotor of each gene is flanked by LoxP sites, were bred with Mx-1Cre mice in which the expression of Cre-recombinase is driven by an interferon (IFN)- α inducible gene promoter. In the resulting VEGFR-1-LoxP.Mx1-Cre and VEGFR-2-LoxP.Mx1-Cre mice, induction of Cre-recombinase expression with IFN- α (or the IFN- α inducer polyinosinic-polycytidylic acid) results in LoxP recombination with 95% efficiency in bone marrow, liver and spleen, and 50% or less efficiency in various organs, including kidney, heart and lung. IFN- α adminstration to newborn VEGFR-1-LoxP(+/+).Mx1-Cre(+) and VEGFR-2-LoxP(+/+).Mx1-Cre(+) adversely affected body mass gain and survival compared to wild-type controls, demonstrating a critical role for both receptors during early postnatal development. In contrast, in these mice, short term genetic ablation of VEGFR-1 and VEGFR-2 in the liver, bone marrow and spleen, beginning at 6 weeks of age did not induce any significant changes in total body or organ mass, indicating that VEGFR-1 and VEGFR-2 are dispensible for survival and maintenance of organ function in adult mice for up to 4 weeks following induction of the knock-out. Data will be presented to illustrate and contrast the consequences of VEGFR-1 and VEGFR-2 genetic ablation in various organs and tissues of newborn and adult VEGFR-1-LoxP.Mx1-Cre and VEGFR-2-LoxP.Mx1-Cre mice injected with IFN- α." @default.
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• W2562840432 date "2005-05-01" @default.
• W2562840432 modified "2023-10-02" @default.
• W2562840432 title "Inducible gene-targeting reveals critical roles for VEGFR-1 and VEGFR-2 during early postnatal development in the mouse" @default.
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