TRANSGENIC MODEL OF INDUCIBLE DIABETES

诱导性糖尿病的转基因模型

• 批准号: 7100952
• 负责人: PEDRO L HERRERA
• 金额: $ 59.4万
• 依托单位: UNIVERSITY OF GENEVA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7100952
• 关键词: biotechnology; cell differentiation; disease /disorder model; genetically modified animals; insulin dependent diabetes mellitus; laboratory mouse; model design /development; pancreatic islet function; pancreatic islets

DESCRIPTION (provided by applicant): We propose the generation of a transgenic model of rapid inducible diabetes. The major aim of this proposal is to determine the origin of insulin-producing beta-cells in adult mice. In these animals, complete, or partial, selective destruction of pancreatic beta-cells will be induced, either during development, during postnatal growth or in adults, upon administration of an inducer drug. These animals will not be engineered to study the pathogenesis of Type I diabetes and the autoimmune mechanisms, nor inflammation; rather, they will be useful to accurately assess islet (beta-cell) neoformation in adult pancreas during the regeneration process that should follow the treatment with the inducer agent. They will also be used in reconstitution assays to determine the differentiation potential of injected stem / progenitor cells, whether i.v. or directly into the pancreas, derived either from pancreatic or extra-pancreatic tissues (e. g. hepatic, neural or hematopoietic stem cells, or ES cell clones). Incidentally, this transgenic model will represent a unique tool to study the involvement of beta-cells in pancreas homeostasis, besides their role of producing insulin. The specific aims are: i) generation of a transgenic model of beta-cell ablation, which will be useful to ii) study beta-cell regeneration and to iii) perform in vivo clonogenic reconstitution assays of transplanted cells. Beyond the basic processes of organ growth and maintenance, this study may have implications for cell replacement therapy in diabetes and for all ethical issues related to the use of embryonic or adult stem cells. Once generated, these transgenic strains will be put into the "public" Beta Cell Biology Consortium (BCBC) mouse repository, so as to become available to the broad scientific community, as we have already done with other transgenic mice that we produced in the past

描述（由申请人提供）： 我们建议建立快速诱导型糖尿病的转基因模型。该提案的主要目的是确定成年小鼠中产生胰岛素的β细胞的起源。在这些动物中，在发育期间、出生后生长期间或在成人中，在给予诱导药物后，将诱导胰腺β细胞的完全或部分选择性破坏。这些动物不会被改造来研究 I 型糖尿病的发病机制和自身免疫机制，也不会研究炎症；相反，它们将有助于准确评估成人胰腺在诱导剂治疗后的再生过程中的胰岛（β细胞）新生。它们还将用于重构测定，以确定注射的干细胞/祖细胞的分化潜力，无论是静脉注射还是注射。或直接进入胰腺，源自胰腺或胰腺外组织（例如肝、神经或造血干细胞，或 ES 细胞克隆）。顺便说一句，除了β细胞产生胰岛素的作用外，这种转基因模型将代表一种独特的工具来研究β细胞在胰腺稳态中的作用。具体目标是：i) 生成 β 细胞消融的转基因模型，这将有助于 ii) 研究 β 细胞再生和 iii) 进行移植细胞的体内克隆重建测定。除了器官生长和维护的基本过程之外，这项研究可能对糖尿病的细胞替代疗法以及与使用胚胎或成体干细胞相关的所有伦理问题产生影响。一旦产生，这些转基因品系将被放入“公共”Beta细胞生物学联盟（BCBC）小鼠储存库，以便为广大科学界提供，就像我们对过去生产的其他转基因小鼠所做的那样