Pancreatic Development in Modeling Pancreatic Disease

描述(由申请人提供)： 胰腺发育在小鼠胰腺疾病模型中的作用 2003年9月4日至5日 西北大学和西北纪念医院 胰腺既有内分泌功能，也有外分泌功能，在血糖稳态和消化方面有不同的作用。当细胞类型发生基因突变、改变细胞功能和/或诱导细胞转化时，就会出现几种几乎没有治愈措施的衰弱疾病。糖尿病、胰腺炎和胰腺癌具有严重的健康后果，从生活质量大大降低开始，最终导致死亡。这些疾病是相互关联的。例如，患有糖尿病和/或胰腺炎的人患胰腺癌的几率更高。为了引入针对这些疾病的治疗范例，关键是要评估临床外的治疗方法，其中包括使用概括这些人类疾病的动物模型。对于这些疾病，确实存在一些小鼠模型，但这些模型很少提供与人类对应的表型或分子模仿。为了更好地了解导致糖尿病、胰腺炎和胰腺癌的连续遗传和细胞事件，并设计用于治疗评估的模型，了解导致分化和细胞命运的潜在机制变得至关重要。在从祖细胞类型到胰腺的三种主要细胞：胰岛细胞、腺泡细胞和导管细胞的途径上，证据正在积累。为了改善胰腺发育和疾病模型研究，我建议召开一次会议，让两个小组聚集在一起。我希望培育一种并不完全到位的关键联系。这种联系是在探索胰腺发育的科学家和决定分化模式和细胞命运的信号之间，以及那些希望在小鼠身上建立胰腺疾病模型的研究人员之间。新的信息定义了哪种胚胎细胞(S)和/或细胞信号(S)负责在胰腺中产生成熟的内分泌和外分泌细胞，这对于设计新的糖尿病、胰腺炎和胰腺癌转基因小鼠模型至关重要。靶向具有各种基因改变的胰腺前体细胞将为发育生物学家和临床病理学家提供有价值的信息。

DESCRIPTION (provided by applicant): The Role of Pancreatic Development in Modeling Pancreatic Disease in Mice. September 4-5, 2003 Northwestern University and Northwestern Memorial Hospital The pancreas serves both an endocrine and exocrine function and has distinct roles in glucose homeostasis and digestion. Several debilitating diseases, with virtually no curative measures, arise when cell types undergo genetic mutations, altering cell function and/or inducing cellular transformation. Diabetes, pancreatitis, and pancreatic cancer have serious health consequences beginning with a greatly reduced quality of life and ending in death. These diseases are associated with each other. For example, people with diabetes and/or pancreatitis have a greater incidence of pancreatic cancer. In order to introduce curative paradigms against these diseases, it is critical to evaluate therapies outside the clinic, which include using animal models that recapitulate these human diseases. A few mouse models do exist for these diseases yet seldom do these models provide phenotypic or molecular mimicry to their human counterpart. To better understand the sequential genetic and cellular events that lead to diabetes, pancreatitis, and pancreatic cancer and engineer models for therapeutic evaluation, it becomes critical to understand the underlying mechanisms responsible for differentiation and cell fate. Evidence is accumulating on the pathway from a progenitor cell type to the three primary cells of the pancreas: islet, acinar, and ductal cells. In order to improve pancreatic development and disease modeling research, I propose holding a conference that brings both groups together. I am hoping to foster a critical link that is not entirely in place. That link is between scientists exploring pancreatic development and the signals that determine differentiation patterns and cell fate with those investigators who desire to model pancreatic disease in mice. New information that defines which embryonic cell(s) and/or cell signal(s) that are responsible for generating mature endocrine and exocrine cells in the pancreas is critical for engineering new transgenic mouse models that recapitulate diabetes, pancreatitis, and pancreatic cancer. Targeting pancreatic progenitor cells with various genetic alterations will provide valuable information for the developmental biologist and clinical pathologist alike.