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

描述（由申请人提供）：在T1 DM和T2 DM动物模型中的SS细胞的多模态成像摘要：SS细胞中成像报告基因的表达为研究SS细胞发育、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），在其ss细胞中表达三种不同的成像报告基因（EGFP-转移酶-胸苷激酶）的融合蛋白。这将使纵向非侵入性成像的ss-细胞在同一动物的CCD和microPET，并确定ss-细胞在细胞水平的荧光显微镜。该提案的目的是提供原则证明，ss细胞的多模态成像可以增强和加速广泛的1型和2型糖尿病（T1 DM和T2 DM）研究。具体目标：1）。三融合报告信号是否提供了一种非侵入性的生物标志物，在饲喂高脂饮食的MIP-TF C57 B16小鼠（一种广泛使用的T2 DM模型）中，β细胞质量增加？2）。MIP-TF C57 BL 6小鼠的ss细胞可以通过microPET进行非侵入性成像吗？3）。在MIP-TF NOD小鼠自发发展为T1 DM的过程中，三融合报告信号与ss细胞质量的损失相关吗？该项目将共同; 1）实现小鼠中ss细胞的第一个microPET成像，这将加快ss细胞成像向临床应用的转化; 2）使研究人员能够通过一种模式收集ss细胞成像数据，并使用该数据预测其他成像模式的结果，并将结果与ss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有助于其他科学家在广泛的领域推进T1 DM和T2 DM研究，包括ss细胞发育，糖尿病发病过程中的ss细胞质量，干细胞分化为ss细胞，转分化和移植后胰岛存活的研究。我们已经产生了转基因小鼠，在其ss细胞中表达一种蛋白质，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。预计这种动物模型将加速广泛的糖尿病研究，包括ss细胞发育，胚胎和成体干细胞分化为ss细胞，转分化，胰岛移植和胰岛成像的研究。

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.