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。 二○ ○三年九月四日至五日 西北大学和西北纪念医院 胰腺具有内分泌和外分泌功能，在葡萄糖稳态和消化中具有不同的作用。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，会出现几种几乎没有治疗措施的衰弱性疾病。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到死亡结束。这些疾病是相互关联的。例如，患有糖尿病和/或胰腺炎的人有更高的胰腺癌发病率。为了引入针对这些疾病的治疗范例，至关重要的是评估临床之外的疗法，包括使用重现这些人类疾病的动物模型。一些小鼠模型确实存在这些疾病，但这些模型很少提供表型或分子模拟其人类对应物。为了更好地理解导致糖尿病、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，理解负责分化和细胞命运的潜在机制变得至关重要。关于从祖细胞类型到胰腺的三种主要细胞（胰岛、腺泡和导管细胞）的途径的证据正在积累。为了改善胰腺发育和疾病建模研究，我建议召开一次会议，将两个小组聚集在一起。我希望促成一个尚未完全到位的关键环节。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与那些希望在小鼠中建立胰腺疾病模型的研究人员之间建立的。定义哪些胚胎细胞和/或细胞信号负责在胰腺中产生成熟的内分泌和外分泌细胞的新信息对于工程化重现糖尿病、胰腺炎和胰腺癌的新转基因小鼠模型至关重要。靶向具有各种遗传改变的胰腺祖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.