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

VE-cadherin-CreERT2 transgenic mouse:: A model for inducible recombination in the endothelium
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DOI:
10.1002/dvdy.20982
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发表时间:
2006-12-01
影响因子:
2.5
通讯作者:
Iruela-Arispe, M. Luisa
Iruela-Arispe, M. Luisa
中科院分区:
生物学3区
文献类型:
--
作者:
Monvoisin, Arnaud;Alva, Jackelyn A.;Iruela-Arispe, M. Luisa

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为了在针对内皮细胞的遗传学实验中引入时间控制,我们建立了在血管内皮细胞钙粘蛋白启动子(VECad)调控下表达他莫昔芬诱导的Cre重组酶(CRE-ERT2)的小鼠系。通过将VECad-CRE-ERT2与ROSA26R报告鼠杂交,证明了Cre活性的特异性和有效性,在ROSA26R报告鼠中,β-半乳糖苷酶基因的上游放置了一个带花环的停止盒。我们发现,他莫昔芬特异性地诱导了胚胎、新生儿和成人组织内皮细胞的广泛重组。重组也被记录在肿瘤相关的血管床和出生后的血管生成试验中。此外,成年动物注射他莫昔芬对造血系的影响可以忽略不计(低于0.4%)。VECad-CRE-ERT2小鼠可能是研究涉及血管发育、动态平衡和涉及新血管生成的复杂过程(如肿瘤生长)的基因功能的有价值的工具。
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.