PDGFRβ-P2A-CreER(T2) mice: a genetic tool to target pericytes in angiogenesis.
PDGFRβ-P2A-CreER(T2) mice: a genetic tool to target pericytes in angiogenesis.
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DOI：
10.1007/s10456-017-9570-9
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发表时间：
2017-11
期刊：
影响因子：
9.8
通讯作者：
Lin CS
中科院分区：
文献类型：
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作者：
Cuervo H;Pereira B;Nadeem T;Lin M;Lee F;Kitajewski J;Lin CS
周细胞是一种重要的壁细胞，其特点是与小口径血管结合，并与内皮细胞共用一层基底膜。周细胞与内皮细胞的相互作用在血管生成中起着重要的作用，然而目前很少有工具可以在小鼠模型中靶向周细胞，限制了我们理解它们的生物学能力。在血小板衍生生长因子受体β启动子的控制下，我们建立了一种新的表达他莫昔芬诱导的Cre-重组酶的小鼠系：PDGFRβ-P2A-CreerT2。将PDGFRβ-P2A-CreERT2与荧光报告基因杂交，检测其在不同时间点新生血管视网膜和脑组织中的表达。报道线显示视网膜和大脑中NG2+、Desmin+、PDGFRβ+血管周围细胞的标记，表明成功地靶向了周细胞；然而，来自报道线的信号也在视网膜和脑中的一小部分神经胶质细胞中观察到。我们还评估了肿瘤中的重组，发现与肿瘤血管相关的血管周围细胞中存在有效的重组。作为原理的证明，我们使用新生成的驱动程序删除了血管周围细胞中的Notch信号，并观察到视网膜动脉中的平滑肌细胞丢失，这与之前发表的评估Notch3基因缺失小鼠的研究一致。我们的结论是，PDGFRβ-P2A-CreERT2系是一种针对周细胞的强大的新工具，将有助于该领域对这些细胞在生理和病理环境中的作用有更深入的了解。
Pericytes are essential mural cells distinguished by their association with small caliber vessels and the presence of a basement membrane shared with endothelial cells. Pericyte interaction with the endothelium plays an important role in angiogenesis, however very few tools are currently available that allow for the targeting of pericytes in mouse models, limiting our ability to understand their biology. We have generated a novel mouse line expressing tamoxifen-inducible Cre-recombinase under the control of the platelet derived growth factor receptor β promoter: PDGFRβ-P2A-CreERT2. We evaluated the expression of the PDGFRβ-P2A-CreERT2 line by crossing it with fluorescent reporter lines and analyzed reporter signal in the angiogenic retina and brain at different time points after tamoxifen administration. Reporter lines showed labeling of NG2+, desmin+, PDGFRβ+ perivascular cells in the retina and the brain, indicating successful targeting of pericytes; however, signal from reporter lines was also observed in a small subset of glial cells both in the retina and the brain. We also evaluated recombination in tumors and found efficient recombination in perivascular cells associated with tumor vasculature. As a proof of principle, we used our newly generated driver to delete Notch signaling in perivascular cells and observed a loss of smooth muscle cells in retinal arteries, consistent with previously published studies evaluating Notch3 null mice. We conclude that the PDGFRβ-P2A-CreERT2 line is a powerful new tool to target pericytes and will aid the field in gaining a deeper understanding of the role of these cells in physiological and pathological settings.
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周细胞损失会影响小鼠的阿尔茨海默氏症样神经变性。
影响因子：
16.6
作者：
Sagare, Abhay P.;Bell, Robert D.;Zhao, Zhen;Ma, Qingyi;Winkler, Ethan A.;Ramanathan, Anita;Zlokovic, Berislav V.
通讯作者：
Zlokovic, Berislav V.
影响因子：
1.5
作者：
Cuttler, Anne S.;LeClair, Renee J.;Stohn, J. Patrizia;Wang, Qiaozeng;Sorenson, Christine M.;Liaw, Lucy;Lindner, Volkhard
通讯作者：
Lindner, Volkhard
影响因子：
3.7
作者：
Kim JH;Lee SR;Li LH;Park HJ;Park JH;Lee KY;Kim MK;Shin BA;Choi SY
通讯作者：
Choi SY
影响因子：
6
作者：
Lin, Shuei-Liong;Kisseleva, Tatiana;Duffield, Jeremy S.
通讯作者：
Duffield, Jeremy S.
DOI：
10.1038/nrg3272
发表时间：
2012-09
期刊：
Nature reviews. Genetics
影响因子：
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作者：
通讯作者：
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