Abnormal angiogenesis but intact hematopoietic potential in TGF-β type I receptor-deficient mice
Abnormal angiogenesis but intact hematopoietic potential in TGF-β type I receptor-deficient mice
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DOI：
10.1093/emboj/20.7.1663
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发表时间：
2001-04-02
期刊：
影响因子：
11.4
通讯作者：
Karlsson, S
中科院分区：
文献类型：
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作者：
Larsson, J;Goumans, MJ;Karlsson, S
小鼠中转化生长因子β 1 （tgf - β 1）基因的缺失先前表明，它调节造血和血管生成。为了更精确地定义tgf - β的功能，我们通过基因靶向灭活tgf - β I型受体（T β RI）基因。缺乏T β - RI的小鼠在妊娠中期死亡，表现出卵黄囊和胎盘血管发育的严重缺陷，并且缺乏循环红细胞。然而，尽管在T β RI-/-卵黄囊中存在明显的贫血，对卵黄囊衍生的造血前体进行的克隆测定显示，与野生型和杂合的兄弟姐妹相比，T β RI-/-小鼠表现出正常的造血潜能，来自T β RI-缺陷胚胎的内皮细胞在体外表现出细胞增殖增强、迁移行为不当和纤维连接蛋白生成受损，这些缺陷与体内血管缺陷有关。因此，我们在这里证明，虽然T β RI在血管发育过程中对tgf - β的功能至关重要，并且不能由激活素受体样激酶-1 （ALK-1）补偿，但功能性造血和造血祖细胞的发育并不依赖于通过T β RI传递的tgf - β信号。
Deletion of the transforming growth factor beta1 (TGF-beta1) gene in mice has previously suggested that it regulates both hematopoiesis and angiogenesis. To define the function of TGF-beta more precisely, we inactivated the TGF-beta type I receptor (T beta RI) gene by gene targeting. Mice lacking T beta RI die at midgestation, exhibiting severe defects in vascular development of the yolk sac and placenta, and an absence of circulating red blood cells. However, despite obvious anemia in the T beta RI-/- yolk sacs, clonogenic assays on yolk sac-derived hematopoietic precursors in vitro revealed that T beta RI-/- mice exhibit normal hematopoietic potential compared with wild-type and heterozygous siblings, Endothelial cells derived from T beta RI-deficient embryos show enhanced cell proliferation, improper migratory behavior and impaired fibronectin production in vitro, defects that are associated with the vascular defects seen in vivo. We thus demonstrate here that, while T beta RI is crucial for the function of TGF-beta during vascular development and can not be compensated for by the activin receptor-like kinase-1 (ALK-1), functional hematopoiesis and development of hematopoietic progenitors is not dependent on TGF-beta signaling via T beta RI.