A transgenic red fluorescent protein-expressing nude mouse for color-coded imaging of the tumor microenvironment.

A transgenic red fluorescent protein-expressing nude mouse for color-coded imaging of the tumor microenvironment.
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转基因红荧光蛋白表达裸小鼠,用于肿瘤微环境的颜色编码成像。

DOI:
10.1002/jcb.21999
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发表时间:
2009-02-01
影响因子:
4
通讯作者:
Hoffman, Robert M.
Hoffman, Robert M.
中科院分区:
生物学2区
文献类型:
--
作者:
Yang, Meng;Reynoso, Jose;Bouvet, Michael;Hoffman, Robert M.

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肿瘤微环境(TME)对于肿瘤的生长和进展至关重要。我们之前使用绿色荧光蛋白(GFP)转基因裸鼠作为宿主开发了 TME 的颜色编码成像。然而,大多数适合 TME 研究的细胞类型供体来源均来自表达 GFP 的小鼠。因此,表达红色荧光蛋白(RFP)的裸鼠将是移植表达GFP的基质细胞以及在细胞核中表达GFP和在细胞质中表达RFP的双标记癌细胞的合适宿主,从而创建TME的三色成像模型。 RFP裸鼠是通过非转基因裸鼠与转基因C57/B6小鼠杂交获得的,其中β-肌动蛋白启动子驱动RFP(DsRed2)在基本上所有组织中表达。在 nu/nu RFP 雄性小鼠和 nu/+ RFP 雌性小鼠的杂交中,胚胎发出红色荧光。这些小鼠的后代中大约 50% 是 RFP 裸鼠。在RFP裸鼠中,心脏、肺、脾、胰腺、食管、胃、十二指肠、雄性和雌性生殖系统均高表达RFP;脑和脊髓;以及循环系统,包括心脏和主要动脉和静脉。带皮骨骼高度表达 RFP。骨髓和脾细胞也呈 RFP 阳性。将表达 GFP 的人类癌细胞系(包括 HCT-116-GFP 结肠癌和 MDA-MB-435-GFP 乳腺癌)原位移植到转基因 RFP 裸鼠中。这些人类肿瘤在转基因 RFP 裸鼠中广泛生长。双色荧光成像使人类肿瘤与宿主相互作用的可视化成为可能。 RFP 裸鼠模型应该会极大地扩展我们对 TME 的了解。
The tumor microenvironment (TME) is critical for tumor growth and progression. We have previously developed color-coded imaging of the TME using a green fluorescent protein (GFP) transgenic nude mouse as a host. However, most donor sources of cell types appropriate for study in the TME are from mice expressing GFP. Therefore, a nude mouse expressing red fluorescent protein (RFP) would be an appropriate host for transplantation of GFP-expressing stromal cells as well as double-labeled cancer cells expressing GFP in the nucleus and RFP in the cytoplasm, thereby creating a three-color imaging model of the TME. The RFP nude mouse was obtained by crossing non-transgenic nude mice with the transgenic C57/B6 mouse in which the β-actin promoter drives RFP (DsRed2) expression in essentially all tissues. In crosses between nu/nu RFP male mice and nu/+ RFP female mice, the embryos fluoresced red. Approximately 50% of the offspring of these mice were RFP nude mice. In the RFP nude mouse, the organs all brightly expressed RFP, including the heart, lungs, spleen, pancreas, esophagus, stomach, duodenum, the male and female reproductive systems; brain and spinal cord; and the circulatory system, including the heart and major arteries and veins. The skinned skeleton highly expressed RFP. The bone marrow and spleen cells were also RFP positive. GFP–expressing human cancer cell lines, including HCT-116-GFP colon cancer and MDA-MB-435-GFP breast cancer were orthotopically transplanted to the transgenic RFP nude mice. These human tumors grew extensively in the transgenic RFP nude mouse. Dual-color fluorescence imaging enabled visualization of human tumor–host interaction. The RFP nude mouse model should greatly expand our knowledge of the TME.
DOI: 10.1073/pnas.97.3.1206
发表时间: 2000-02-01
影响因子: 11.1
作者:
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发表时间: 2003-06-01
期刊: BIOTECHNIQUES
影响因子: 2.7
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通讯作者: Laug, WE
DOI: 10.1016/j.tibtech.2007.10.006
发表时间: 2008-01-01
影响因子: 17.3
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DOI: 10.2144/05392bm02
发表时间: 2005-08-01
期刊: BIOTECHNIQUES
影响因子: 2.7
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