Mast cell effects on islet cell destruction in NOD mice

描述（由申请人提供）：肥大细胞是在变态反应研究领域得到最好研究的强效炎症细胞。最近的证据已经确定了肥大细胞在自身免疫性疾病如多发性硬化症和关节炎的小鼠模型中的作用。肥大细胞通常存在于胰腺中，并且在胰腺的炎性病症如胰腺炎中数量增加。此外，它们是介体的重要生产者，已知介体调节T细胞反应，引发导致糖尿病的炎症。假设肥大细胞影响导致胰岛β细胞破坏的炎症事件。为了测试这一点，我们将利用肥大细胞缺陷小鼠模型。将产生肥大细胞缺陷表型（两种不同的ckit突变）的基因繁殖到NOD/Lt小鼠背景中，并评价对糖尿病前期和糖尿病指数的影响。具体目标是：1.开发和表征肥大细胞缺陷NOD小鼠系2。探讨肥大细胞缺乏对自发性胰岛炎和糖尿病发生的影响。3.确定肥大细胞在糖尿病发生发展中的作用部位。

DESCRIPTION (provided by applicant): Mast cells are potent inflammatory cells that have been best studied in the realm of allergy research. Recent evidence has established a role for mast cells in murine models of autoimmune diseases such as multiple sclerosis and arthritis. Mast cells are normally present in the pancreas and increase in numbers in inflammatory conditions of the pancreas such as pancreatitis. In addition, they are important producers of mediators that are known to regulate T cell responses that initiate the inflammation that contributes to diabetes. It is hypothesized that mast cells influence inflammatory events that lead to pancreatic islet beta cell destruction. To test this, we will utilize a mast cell-deficient mouse model. Genes that give rise to a mast cell-deficient phenotype (two distinct ckit mutations) will be bred onto the NOD/Lt mouse background and the effects on indices of pre-diabetes and diabetes will be evaluated. The specific aims are: 1. To develop and characterize a line of mast cell-deficient NOD mice 2. To examine the consequencess of mast cell-deficiency on the development of spontaneous insulitis and diabetes. 3. To determine the sites of mast cell influence on diabetes development.