FAILURE OF BLOOD-ISLAND FORMATION AND VASCULOGENESIS IN FLK-1-DEFICIENT MICE
FAILURE OF BLOOD-ISLAND FORMATION AND VASCULOGENESIS IN FLK-1-DEFICIENT MICE
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DOI：
10.1038/376062a0
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发表时间：
1995-07-06
期刊：
影响因子：
64.8
通讯作者：
SCHUH, AC
中科院分区：
文献类型：
--
作者：
SHALABY, F;ROSSANT, J;SCHUH, AC
酪氨酸激酶受体Flk-1（参考文献1）被认为在内皮细胞的发育中起关键作用。Flk-1受体的表达仅限于内皮细胞及其胚胎前体细胞（2-5），并与其配体血管内皮生长因子（VEGF）互补（2,3），后者是内皮特异性丝裂原。flk-1的最高表达水平出现在胚胎血管生成和血管生成（2-5），以及与新生血管形成相关的病理过程，如肿瘤血管生成（7,8）。由于早在性交后7天就可以在假定的中胚层卵黄囊血岛祖细胞中检测到flk-1的表达，因此flk-1可能标志着假定的常见胚胎内皮细胞和造血前体细胞，即成血管细胞，因此也可能参与早期造血(4)。本文报道了在胚胎干细胞中利用同源重组破坏Flk-1基因而产生Flk-1缺陷的小鼠。由于造血细胞和内皮细胞发育的早期缺陷，这种突变的纯合子胚胎在性交后8.5至9.5天内死亡。7.5 d时卵黄囊血岛消失，胚内及卵黄囊内均未见有组织血管，酸性造血祖细胞严重减少。这些结果表明，Flk-1在小鼠胚胎卵黄囊心境岛形成和血管发生中起重要作用。
THE receptor tyrosine kinase Flk-1 (ref. 1) is believed to play a pivotal role in endothelial development. Expression of the Flk-1 receptor is restricted to endothelial cells and their embryonic precursors(2-5), and is complementary to that of its ligand, vascular endothelial growth factor (VEGF)(2,3), which, is aa endothelial-specific mitogen. Highest levels of flk-1 expression are observed during embryonic vasculogenesis and angiogenesis(2-5), and dating pathological processes associated with neovascularization, such its tumour angiogenesis(7,8). Because flk-1 expression can be detected in presumptive mesodermal yolk-sac blood-island progenitors as early as 7.0 days postcoitum, Flk-1 may mark the putative common embryonic endothelial and haematopoietic precursor, the haemangioblast, and thus may also be involved in early haematopoiesis(4). Here rye report the generation of mice deficient in Flk-1 by disruption of the gene using homologous recombination in embryonic stem (ES) cells. Embryos homozygous for this mutation die in utero between 8.5 and 9.5 days post-coitum, as a result of an early defect in the development of haematopoietic and endothelial cells. Yolk-sac blood islands were absent at 7.5 days, organized blood vessels could not be observed in the embryo or yolk sac at any stage, acid haematopoietic progenitors were severely reduced. These results indicate that Flk-1 is essential for yolk-sac Mood-island formation and vasculogenesis in the mouse embryo.