Loss of Endothelial Tie1 Receptor Impairs Lymphatic Vessel Development-Brief Report
Loss of Endothelial Tie1 Receptor Impairs Lymphatic Vessel Development-Brief Report
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DOI：
10.1161/atvbaha.109.196618
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发表时间：
2010-02-01
影响因子：
8.7
通讯作者：
Alitalo, Kari
中科院分区：
文献类型：
--
作者：
D'Amico, Gabriela;Korhonen, Emilia Anne;Alitalo, Kari
目的：对Tie1基因靶向胚胎的研究已证实血管完整性丧失，但Tie1与淋巴管发育的相关性尚不清楚。我们验证了Tie1突变胚胎中观察到的肿胀与淋巴管缺陷有关的假设。方法和结果-我们可以在ICR背景下延长Tie1缺陷胚胎的存活时间，这使我们能够研究它们的淋巴管发育。胚胎发育14.5d时，Tie1(-/-)胚胎出现水肿和出血，并开始死亡。免疫组织化学分析显示，它们有异常的淋巴囊。Tie1(-/-)突变体在E12.5时已经肿胀，没有出血迹象。他们的淋巴囊有异常的图案，表明淋巴管畸形先于血管缺陷。我们产生了条件Cre/loxP Tie1(Neo)基因座的小鼠，发现纯合子Tie1(neo/neo)亚型胚胎存活到E15.5，淋巴管畸形类似于Tie1(-/-)突变。结论-我们的数据表明Tie1缺失会导致血管表型之前的淋巴管异常。这些发现表明Tie1参与了淋巴管的生成，并提示在两个血管间隔中对Tie1信号的不同要求。(动脉血栓血管生物)2010；30：207-209。)
Objective-Studies of Tie1 gene-targeted embryos have demonstrated loss of blood vessel integrity, but the relevance of Tie1 in lymphatic vasculature development is unknown. We tested the hypothesis that the swelling observed in Tie1 mutant embryos is associated with lymphatic vascular defects.Methods and Results-We could extend the survival of the Tie1-deficient embryos in the ICR background, which allowed us to study their lymphatic vessel development. At embryonic day (E) 14.5, the Tie1(-/-) embryos had edema and hemorrhages and began to die. Immunohistochemical analysis revealed that they have abnormal lymph sacs. Tie1(-/-) mutants were swollen already at E12.5 without signs of hemorrhage. Their lymph sacs were abnormally patterned, suggesting that lymphatic malformations precede the blood vascular defects. We generated mice with a conditional Cre/loxP Tie1(neo) locus and found that the homozygous Tie1(neo/neo) hypomorphic embryos survived until E15.5 with lymphatic malformations resembling those seen in the Tie1(-/-) mutants.Conclusion-Our data show that loss of Tie1 results in lymphatic vascular abnormalities that precede the blood vessel phenotype. These findings indicate that Tie1 is involved in lymphangiogenesis and suggest differential requirements for Tie1 signaling in the two vascular compartments. (Arterioscler Thromb Vasc Biol. 2010; 30: 207-209.)