Use of the ODD-luciferase transgene for the non-invasive imaging of spontaneous tumors in mice.
Use of the ODD-luciferase transgene for the non-invasive imaging of spontaneous tumors in mice.
复制标题
DOI：
10.1371/journal.pone.0018269
复制
发表时间：
2011-03-29
期刊：
影响因子：
3.7
通讯作者：
Jin S
中科院分区：
文献类型：
--
作者：
Goldman SJ;Chen E;Taylor R;Zhang S;Petrosky W;Reiss M;Jin S
在人类中，肿瘤的成像提供了对肿瘤生长和位置的快速、准确的评估。然而，在实验动物中，自发发生的肿瘤的成像继续带来许多技术和后勤问题。最近建立了一种小鼠模型，在该模型中，由HIF-1α氧依赖降解结构域(ODD)与荧光素酶融合而成的嵌合蛋白在所有组织中普遍表达。低氧应激导致奇-荧光素酶在该模型小鼠的组织中积累，这可以通过非侵入性生物发光测量来识别。由于实体肿瘤通常包含缺氧区，我们进行了原则验证实验，以测试该转基因小鼠模型是否可以用作自发实体肿瘤的非侵入性成像分析的通用平台。用MMTV-neu/BELIN1+/−小鼠培育奇荧光素酶转基因小鼠。注射荧光素后，用IVIS光谱成像仪非侵入性地测量转基因小鼠正常组织的生物发光背景和自发性乳腺癌的生物发光信号。手动测量肿瘤体积，并对肿瘤组织进行组织学分析。我们的结果表明，奇数荧光素酶转基因小鼠的自发乳腺肿瘤产生了大量的生物发光信号，这些信号与背景组织的发光明显区分开来。此外，我们还证明了生物发光肿瘤轮廓和可触及的肿瘤体积之间存在很强的定量相关性。我们进一步证明，使用该系统可以定量地确定自发性肿瘤对化疗的反应体积的缩小。最后，我们表明，自发性肿瘤的生长和发展可以在几周内进行纵向监测。因此，我们的结果表明，该模型可能为小鼠自发性实体瘤的成像提供一种实用、可靠和经济有效的非侵入性定量方法。
In humans, imaging of tumors provides rapid, accurate assessment of tumor growth and location. In laboratory animals, however, the imaging of spontaneously occurring tumors continues to pose many technical and logistical problems. Recently a mouse model was generated in which a chimeric protein consisting of HIF-1α oxygen-dependent degradation domain (ODD) fused to luciferase was ubiquitously expressed in all tissues. Hypoxic stress leads to the accumulation of ODD-luciferase in the tissues of this mouse model which can be identified by non-invasive bioluminescence measurement. Since solid tumors often contain hypoxic regions, we performed proof-of-principle experiments testing whether this transgenic mouse model may be used as a universal platform for non-invasive imaging analysis of spontaneous solid tumors. ODD-luciferase transgenic mice were bred with MMTV-neu/beclin1+/− mice. Upon injection of luciferin, bioluminescent background of normal tissues in the transgenic mice and bioluminescent signals from spontaneously mammary carcinomas were measured non-invasively with an IVIS Spectrum imaging station. Tumor volumes were measured manually and the histology of tumor tissues was analyzed. Our results show that spontaneous mammary tumors in ODD-luciferase transgenic mice generate substantial bioluminescent signals, which are clearly discernable from background tissue luminescence. Moreover, we demonstrate a strong quantitative correlation between the bioluminescent tumor contour and the volume of palpable tumors. We further demonstrate that shrinkage of the volume of spontaneous tumors in response to chemotherapeutic treatment can be determined quantitatively using this system. Finally, we show that the growth and development of spontaneous tumors can be monitored longitudinally over several weeks. Thus, our results suggest that this model could potentially provide a practical, reliable, and cost-effective non-invasive quantitative method for imaging spontaneous solid tumors in mice.
登录
查看更多内容
影响因子：
9.2
作者：
MULLER, WJ
通讯作者：
MULLER, WJ
影响因子：
2.5
作者：
Albanell, J;Baselga, J
通讯作者：
Baselga, J
DOI：
10.1073/pnas.2436255100
发表时间：
2003-12-09
影响因子：
11.1
作者：
Yue, ZY;Jin, SK;Heintz, N
通讯作者：
Heintz, N
影响因子：
64.5
作者：
MULLER, WJ;SINN, E;LEDER, P
通讯作者：
LEDER, P
影响因子：
2.5
作者：
Stern, David F.
通讯作者：
Stern, David F.