Generation of a Novel Transgenic Mouse Model for Bioluminescent Monitoring of Survivin Gene Activity in Vivo at Various Pathophysiological Processes Survivin Expression Overlaps with Stem Cell Markers
Generation of a Novel Transgenic Mouse Model for Bioluminescent Monitoring of Survivin Gene Activity in Vivo at Various Pathophysiological Processes Survivin Expression Overlaps with Stem Cell Markers
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DOI：
10.2353/ajpath.2010.090414
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发表时间：
2010-04-01
影响因子：
6
通讯作者：
Porter, Carl W.
中科院分区：
文献类型：
--
作者：
Li, Fengzhi;Cheng, Qiuying;Porter, Carl W.
生存已牵连发挥重要作用，在各种病理生理过程。然而，由于缺乏合适的动物模型，生存素在病理生理过程中的作用和动态表达还没有很好的定义。我们产生了一个人生存素基因启动子驱动的荧光素酶转基因小鼠模型（SPlucTg），使动态生存素基因的活性可以在各种病理生理条件下，使用体内成像监测。我们的研究结果表明，与睾丸中存活素阳性一致，在正常SPlucTg小鼠中，在雄性小鼠的睾丸中检测到荧光素酶活性。此外，类似于已知的生存素的瞬时表达的病理生理反应的要求，我们观察到一个瞬时的荧光素酶表达去势SPlucTg雄性小鼠补充雄激素后。值得注意的是，据报道，存活素表达在小鼠肝损伤和再生过程中开启;在将四氯化碳给予SPlucTg小鼠后，观察到小鼠肝脏中的瞬时和剂量依赖性荧光素酶表达。我们进一步证明了荧光素酶活性与内源性生存素表达密切相关。我们还证明，只有一个子集的细胞表达生存素，其表达与几个干细胞标志物的表达测试重叠。因此，我们已经产生了一个独特的动物模型，用于分析不同的病理生理过程和可能的干细胞分布/活性在体内。(Am J Pathol 2010，176：1629-1638; DOI：10.2353/ajpath.2010.090414）
Survival has been implicated to play an important role in various pathophysiological processes. However, because of a lack of appropriate animal models, the role and dynamic expression of survivin during pathophysiology are not well defined. We generated a human survivin gene promoter-driven luciferase transgenic mouse model (SPlucTg) so that dynamic survivin gene activity can be monitored during various pathophysiological conditions using in vivo imaging. Our results show that, consistent with survivin positivity in testis, luciferase activity in normal SPlucTg mice was detected in the testis of male mice. Furthermore, similar to the known requirement of transient expression of survivin for pathophysiological responses, we observed a transient luciferase expression in castrated SPlucTg male mice after supplement of androgen. Significantly, it was reported that survivin expression turns on during mouse liver injury and regeneration; a transient and dose-dependent luciferase expression in the mouse liver was observed after administration of carbon tetrachloride into SPlucTg mice. We further demonstrated that luciferase activity closely correlates with endogenous survivin expression. We also demonstrated that only a subset of cells expresses survivin, and its expression overlaps with the expression of several stem cell markers tested. Thus, we have generated a unique animal model for analysis of diverse pathophysiological processes and possible stem cell distribution/activity in vivo. (Am J Pathol 2010, 176:1629-1638; DOI: 10.2353/ajpath.2010.090414)