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Noninvasive Monitoring of β-Cell Mass and Fetal β-Cell Genesis in Mice Using Bioluminescence Imaging

机译：利用生物发光成像技术无创监测小鼠β细胞质量和胎儿β细胞发生

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Bioluminescence imaging (BLI) has been applied in gene therapy and research to screen for transgene expression, progression of infection, tumor growth and metastasis, and transplantation. It enables real-time and relatively noninvasive localization and serial quantification of biological processes in experimental animals. In diabetes research, BLI has been employed for the quantification of β-cell mass, monitoring of islet graft survival after transplantation, and detection of reporter gene expression. Here, we explore the use of BLI in a transgenic mouse expressing luciferase under the control of the mouse insulin 1 promoter (MIP-Luc-VU). A previous report on MIP-Luc-VU mice showed luminescence intensities emitted from the islets correlated well with the number of islets in vitro and in vivo . In this study, we showed MIP-Luc-VU mice fed a high fat diet for 8 weeks gave rise to a greater bioluminescent signal than mice fed a regular diet for the same period of time. Conversely, there was a strong reduction in the signal observed in diabetic Mafa -deficient/ Mafk -transgenic mutant mice and streptozotocin-treated mice, reflecting the loss of β-cells. Furthermore, we were able to monitor fetal β-cell genesis in MIP-Luc-VU mice during the late gestational stage in a noninvasive and repetitive manner. In summary, we show that bioluminescence imaging of mice expressing a β-cell specific reporter allows detection of changes in β-cell mass and visualization of fetal β-cell neogenesis in uteri.
机译：生物发光成像（BLI）已应用于基因治疗和研究中，以筛选转基因表达，感染进展，肿瘤生长和转移以及移植。它可以对实验动物的生物过程进行实时且相对无创的定位和系列定量。在糖尿病研究中，BLI已用于量化β细胞质量，监测移植后胰岛移植物的存活以及检测报告基因的表达。在这里，我们探索在小鼠胰岛素1启动子（MIP-Luc-VU）的控制下表达荧光素酶的转基因小鼠中BLI的使用。先前有关MIP-Luc-VU小鼠的报道显示，胰岛发出的发光强度与体内和体外的胰岛数量密切相关。在这项研究中，我们显示，喂食高脂饮食8周的MIP-Luc-VU小鼠比喂食相同时间相同饮食的小鼠产生更大的生物发光信号。相反，在糖尿病Mafa缺陷/ Mafk转基因突变小鼠和链脲佐菌素治疗的小鼠中观察到的信号强烈降低，反映了β细胞的损失。此外，我们能够以无创和重复的方式监测妊娠后期MIP-Luc-VU小鼠中胎儿β细胞的发生。总而言之，我们显示了表达β细胞特异性报告基因的小鼠的生物发光成像可以检测β细胞质量的变化并可视化子宫中胎儿β细胞的新生。

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