TARGETED DISRUPTION OF THE MURINE VCAM1 GENE - ESSENTIAL ROLE OF VCAM-1 IN CHORIOALLANTOIC FUSION AND PLACENTATION
TARGETED DISRUPTION OF THE MURINE VCAM1 GENE - ESSENTIAL ROLE OF VCAM-1 IN CHORIOALLANTOIC FUSION AND PLACENTATION
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DOI：
10.1101/gad.9.1.1
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发表时间：
1995-01-01
影响因子：
10.5
通讯作者：
CYBULSKY, MI
中科院分区：
文献类型：
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作者：
GURTNER, GC;DAVIS, V;CYBULSKY, MI
血管细胞粘附分子-1（VCAM-1）在多种炎症条件下表达于血管内皮上，并介导白细胞从血液募集到组织中。在这项研究中，我们报告了一个新的作用VCAM-1在形成的脐带和胎盘在发展过程中。小鼠VCAM 1基因被破坏的靶向同源重组，并在VCAM-1缺陷的胚胎中发现一个独特的表型。在妊娠8.5天时，尿囊未能与绒毛膜融合，导致胎盘发育异常，胚胎在1-3天内死亡。此外，还观察到VCAM-1在绒膜尿囊融合后早期胎盘形成中的作用。在少数VCAM-1缺陷的胚胎中，尿囊能够与绒毛膜融合，但尿囊中胚层异常分布在绒毛膜表面。少数VCAM-1缺陷的胚胎存活下来，可能是通过绕过胎盘形成缺陷。它们变成了可存活和可生育的成年小鼠，缺乏VCAM-1表达，器官正常，循环血液单核白细胞数量增加。
Vascular cell adhesion molecule-1 (VCAM-1) is expressed on vascular endothelium in a variety of inflammatory conditions and mediates leukocyte recruitment from blood into tissues. In this study we report a novel role for VCAM-1 in the formation of the umbilical cord and placenta during development. The murine VCAM1 gene was disrupted by targeted homologous recombination, and a distinct phenotype was found in VCAM-1-deficient embryos. At 8.5 days of gestation, the allantois failed to fuse to the chorion, resulting in abnormal placental development and embryonic death within 1-3 days. In addition, a role for VCAM-1 in early placental formation after chorioallantoic fusion was observed. In a minority of VCAM-1-deficient embryos, the allantois was able to fuse with the chorion, but the allantoic mesoderm was abnormally distributed over the chorionic surface. A small number of VCAM-1-deficient embryos survived, presumably by circumventing the placentation defects. They became viable and fertile adult mice with lack of VCAM-1 expression, normal organs, and an elevated number of circulating blood mononuclear leukocytes.