Multimodality imaging of beta-cell in anaimal models of T1DM and T2DM

摘要：ss细胞中影像学报告基因的表达为研究ss细胞的发育、糖尿病和胰岛移植提供了有力的工具。我们已经产生了转基因小鼠（MIP-TF小鼠），在它们的细胞中表达三种不同成像报告蛋白（EGFP-荧光素酶-胸苷激酶）的融合蛋白。这将使通过CCD和microPET对同一动物的ss细胞进行纵向无创成像，并通过荧光显微镜在细胞水平上识别ss细胞成为可能。该提案的目的是提供ss细胞的多模态成像可以扩大和加快1型和2型糖尿病（T1DM和T2DM）研究的原理证明。具体目标：1)；作为一种广泛应用的T2DM模型，融合报告信号是否为高脂饮食的MIP-TF C57Bl6小鼠提供了一种非侵入性的细胞质量增加的生物标志物？2）. MIP-TF C57BL6小鼠的细胞能否无创成像？3）. 在MIP-TF NOD小鼠T1DM自发发展过程中，融合报告信号是否与ss-细胞质量损失相关？总之，这个项目将；1)实现小鼠细胞的首次微pet成像，这将加快细胞成像向临床应用的转化；2)使研究人员能够通过一种方式收集细胞成像数据，并使用该数据预测其他成像方式的结果，并将结果与细胞质量等同起来。我们预计，该项目将产生的数据和转基因小鼠将帮助其他科学家在广泛的前沿推进T1DM和T2DM的研究，包括研究ss细胞发育，糖尿病发病过程中的ss细胞质量，干细胞向ss细胞的分化，转分化和移植后胰岛存活。摘要：我们已经产生了在其ss细胞中表达一种蛋白质的转基因小鼠，这应该使研究人员能够通过三种不同的成像技术对活体动物中的ss细胞进行成像，从而使研究人员能够在活体动物和组织切片的细胞水平上监测ss细胞。预计该动物模型将促进广泛的糖尿病研究，包括研究ss细胞发育，胚胎和成体干细胞向ss细胞分化，转分化，胰岛移植和胰岛成像。

DESCRIPTION (provided by applicant): Multimodality imaging of ss-cells in animal models of T1DM and T2DM Abstract: The expression of imaging reporter genes in ss-cells has provided powerful tools for studying ss-cell development, diabetes and islet transplantation. We have generated transgenic mice (MIP-TF mice) that express a fusion protein of three different imaging reporters (EGFP- luciferase-thymidine kinase) in their ss-cells. This should enable the longitudinal noninvasive imaging of ss-cells in the same animal by CCD and microPET, and the identification of ss-cells at the cellular level by fluorescent microscopy. The goals of this proposal are designed to provide proof-of-principle that multimodality imaging of ss-cells can augment and expedite a broad range of type 1 and type 2 diabetes mellitus (T1DM and T2DM) studies. Specific Aims: 1). Do trifusion reporter signals provide a noninvasive biomarker of the gain of ss-cell mass in MIP-TF C57Bl6 mice fed a high fat diet, a widely used model of T2DM? 2). Can the ss-cells of MIP-TF C57BL6 mice be noninvasively imaged by microPET? 3). Do trifusion reporter signals correlate with the loss of ss-cell mass during the spontaneous development of T1DM in MIP-TF NOD mice? Together, this project will; 1) enable the first microPET imaging of ss-cells in mice, which would expedite the translation of ss-cell imaging to clinical applications and; 2) enable researchers to collect ss-cell imaging data by one modality and use this data to predict the results of other imaging modalities, and equate the results with ss-cell mass. We anticipate that the data and transgenic mice that this project will generate will help other scientists to advance T1DM and T2DM research on a broad number of fronts, including studies of ss-cell development, ss-cell mass during diabetes pathogenesis, stem cell differentiation into ss-cells, transdifferentiation, and islet survival after transplantation. PUBLIC HEALTH RELEVANCE Laypersons abstract: We have generated transgenic mice that express a protein in their ss-cells that should enable researchers to image ss-cells in living animals by three different imaging techniques, allowing researchers to monitor ss-cells in living animals and at the cellular level in tissue sections. It is expected that this animal model will expedite a broad range of diabetes research, including studies of ss-cell development, embryonic and adult stem cell differentiation into ss-cells, transdifferentiation, islet transplantation and islet imaging.