The generation of the endothelial specific cdc42-deficient mice and the effect of cdc42 deletion on the angiogenesis and embryonic development
The generation of the endothelial specific cdc42-deficient mice and the effect of cdc42 deletion on the angiogenesis and embryonic development
复制标题
内皮特异性cdc42缺陷小鼠的产生以及cdc42缺失对血管生成和胚胎发育的影响
DOI：
10.3760/cma.j.issn.0366-6999.2011.24.007
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发表时间：
2011-12-20
影响因子：
6.1
通讯作者：
Zhang Lin
中科院分区：
文献类型：
--
作者：
Hu Guo-dong;Chen Ying-hua;Zhang Lin
背景高微血管通透性在感染性休克、急性肺损伤和急性呼吸窘迫综合征、烧伤等多种疾病的病理过程中起重要作用。抑制高渗透性对于控制这些条件是重要的。Cdc 42作为小Rho GT3家族的主要成员，在控制和调节内皮连接通透性方面起着关键作用。我们的目的是通过Cre/loxp重组方法产生和鉴定内皮特异性cdc 42缺陷小鼠，用于在动物模型中检查cdc 42基因在微血管屏障功能中的贡献。（Flox/Flox）小鼠与表达内皮细胞特异性Cre重组酶的小鼠，将基因型为cdc 42（Flox/+）Tie 2Cre（+/-）的后代与cdc 42（Flox/Flox）小鼠回交。F2代中的cdc 42（Flox/Flox）Tie 2Cre（+/-）小鼠是靶小鼠。结果Cdc 42（Flox/Flox）Cre（+/-）小鼠与cdc 42（Flox/Flox）小鼠交配，存活的子代中无cdc 42（Flox/Flox）Cre（+/-）靶小鼠。在E7.5-E16.5期发现了内皮特异cdc 42缺陷的胚胎。我们观察到cdc 42缺陷的胚胎更小，有更少的血管，并有点肿胀相比wild-type embryos.Conclusions内皮特异性敲除cdc 42导致胚胎死亡，小鼠没有存活到出生。与野生型胚胎相比，目标胚胎要小得多，血管更少，肿胀程度更高。这些结果表明cdc 42在胚胎发育和微血管发育以及微血管通透性中起重要作用。中华医学杂志2011;124（24）：4155-4159
Background High microvascular permeability plays an essential role in pathological process of multiple diseases such as septic shock, acute lung injury and acute respiratory distress syndrome, and burns. Inhibiting hyperpermeability is significant for controlling these conditions. Cdc42, as a main member of the small Rho GTPase family, plays a critical role in controlling and regulating the endothelial junctional permeability. We aimed to generate and identify endothelial specific cdc42-deficient mice by the Cre/loxp recombination approach, for examination in an animal model of the contribution of the cdc42 gene in the microvascular barrier function.Methods We crossed cdc42(Flox/Flox) mice with mice expressing endothelial cell-specific Cre recombinase, and the offspring with the genotype cdc42(Flox/+)Tie2Cre(+/-) were back-crossed with the cdc42(Flox/Flox) mice. The cdc42(Flox/Flox)Tie2Cre(+/-) mice in the F2 generation were the target mice. If the cdc42 deficient mice did not survive, we would observe the cdc42 deficient mice embryos, and compare them with wild-type mice embryos.Results Cdc42(flox/+)Cre(+/-) mice were mated with the cdc42(Flox/Flox) mice and among the living offspring there were no cdc42(Flox/Flox)Cre(+/-) target mice. We found the endothelial special cdc42 deficient embryos at the E7.5-E16.5 stage. We observed that cdc42 deficient embryos were much smaller, had fewer vessels and were a little more swollen compared with the wild-type embryos.Conclusions Endothelial specific knockout of cdc42 caused embryonic lethality and the mice did not survive to birth. The target embryos were much smaller, had fewer vessels and were a little more swollen compared with the wild-type embryos. These results demonstrated that the cdc42 plays an important role in development of embryos and in development of microvessels as well as microvascular permeability. Chin Med J 2011;124(24):4155-4159