Gurtner G C, Davis V, Li H, McCoy M J, Sharpe A, Cybulsky M I
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
Genes Dev. 1995 Jan 1;9(1):1-14. doi: 10.1101/gad.9.1.1.
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.
血管细胞黏附分子-1（VCAM-1）在多种炎症条件下的血管内皮细胞上表达，并介导白细胞从血液进入组织。在本研究中，我们报告了VCAM-1在发育过程中脐带和胎盘形成中的新作用。通过靶向同源重组破坏了小鼠VCAM1基因，在缺乏VCAM-1的胚胎中发现了明显的表型。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，观察到VCAM-1在绒毛膜尿囊融合后早期胎盘形成中的作用。在少数缺乏VCAM-1的胚胎中，尿囊能够与绒毛膜融合，但尿囊间充质在绒毛膜表面分布异常。少数缺乏VCAM-1的胚胎存活下来，可能是通过规避胎盘形成缺陷。它们成为了有活力且可育的成年小鼠，缺乏VCAM-1表达，器官正常，循环血液单核白细胞数量增加。
