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血管内皮钙黏蛋白-CreERT2转基因小鼠:一种用于内皮细胞诱导性重组的模型。

VE-cadherin-CreERT2 transgenic mouse: a model for inducible recombination in the endothelium.

作者信息

Monvoisin Arnaud, Alva Jackelyn A, Hofmann Jennifer J, Zovein Ann C, Lane Timothy F, Iruela-Arispe M Luisa

机构信息

Department of Molecular Cellular and Developmental Biology, UCLA, Los Angeles, California 90095, USA.

出版信息

Dev Dyn. 2006 Dec;235(12):3413-22. doi: 10.1002/dvdy.20982.

Abstract

To introduce temporal control in genetic experiments targeting the endothelium, we established a mouse line expressing tamoxifen-inducible Cre-recombinase (Cre-ERT2) under the regulation of the vascular endothelial cadherin promoter (VECad). Specificity and efficiency of Cre activity was documented by crossing VECad-Cre-ERT2 with the ROSA26R reporter mouse, in which a floxed-stop cassette has been placed upstream of the beta-galactosidase gene. We found that tamoxifen specifically induced widespread recombination in the endothelium of embryonic, neonatal, and adult tissues. Recombination was also documented in tumor-associated vascular beds and in postnatal angiogenesis assays. Furthermore, injection of tamoxifen in adult animals resulted in negligible excision (lower than 0.4%) in the hematopoietic lineage. The VECad-Cre-ERT2 mouse is likely to be a valuable tool to study the function of genes involved in vascular development, homeostasis, and in complex processes involving neoangiogenesis, such as tumor growth.

摘要

为了在针对内皮细胞的基因实验中引入时间控制,我们建立了一种小鼠品系,该品系在血管内皮钙黏蛋白启动子(VECad)的调控下表达他莫昔芬诱导型Cre重组酶(Cre-ERT2)。通过将VECad-Cre-ERT2与ROSA26R报告基因小鼠杂交,记录了Cre活性的特异性和效率,在ROSA26R报告基因小鼠中,一个loxP-STOP盒被置于β-半乳糖苷酶基因的上游。我们发现,他莫昔芬特异性地诱导胚胎、新生和成年组织内皮细胞中的广泛重组。在肿瘤相关血管床和出生后血管生成试验中也记录到了重组。此外,在成年动物中注射他莫昔芬导致造血谱系中的切除率可忽略不计(低于0.4%)。VECad-Cre-ERT2小鼠可能是研究参与血管发育、稳态以及涉及新生血管生成的复杂过程(如肿瘤生长)的基因功能的有价值工具。

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