Modeling Sjogrens Syndrome with Id3 Conditional Knockout Mice

描述（由申请人提供）：格林综合征是最常见的风湿性自身免疫性疾病之一，影响美国约400万人，其中大多数是中年妇女。这种疾病是由泪腺和唾液腺的慢性炎症引起的，导致持续的眼睛和嘴巴干燥，以及涉及许多其他器官（如关节、肾脏和肺）的全身问题。在我的实验室进行的研究表明，Id3-/-小鼠会患上原发性Sj" green 's综合征。该小鼠模型为进一步了解Sj"gren's综合征的病因提供了独特的遗传工具。我们最近对Id3缺陷小鼠的研究表明，34个T细胞在这种疾病模型中起作用。这一新发现特别有趣，因为在临床病例报告中有34个T细胞与格林综合征有关。我们计划使用一个Id3条件等位基因来研究Id3在疾病发展中的谱系和阶段特异性需求。拟议研究的结果应该建立特定细胞谱系中特定发育阶段的Id3功能与Sj" green 's综合征之间的因果关系。34 T细胞参与这种疾病模型，如果被证明是真的，将是特别新颖的，并指出了临床应用的新方向。相关性：本提案是为了响应国家研究资源中心的项目公告（PA-07-336），该公告呼吁开发用于研究的动物模型和相关生物材料。我们计划建立一种新的研究格林综合征的动物模型，并将该模型提供给科学界进行相关研究。格林氏综合征是最普遍的风湿性自身免疫性疾病之一，影响着美国大约400万人，其中大多数是中年妇女。这种疾病是由免疫细胞对泪腺和唾液腺的慢性攻击引起的，导致眼睛和嘴巴持续干燥。在我的实验室进行的工作表明，缺乏Id3的小鼠会患上原发性格林综合征。然而，这种动物模型的发病机制目前尚不清楚。我们最近的工作提出了一个新的假设，即34个T细胞中Id3的缺失可能足以引发Sj" green 's综合征。为了验证这一假设并建立一个更明确的动物模型，我们计划创建Id3条件敲除小鼠，在34个T细胞中完全消除Id3。我们将在这个新的动物模型中评估与Sj"gren's综合征相关的表型。

DESCRIPTION (provided by applicant): Sj"gren's syndrome is one of the most prevalent rheumatic autoimmune disease affecting approximately 4 million people in this country, mostly women reaching middle age. The disease is caused by chronic inflammation of the lachrymal and salivary glands, resulting in persistent dry eyes and mouth and systemic problems involving many other organs such as joints, kidney, and lung. Work carried out in my laboratory demonstrated that Id3-/- mice develop primary Sj"gren's syndrome. This mouse model provides a unique genetic tool for further understanding the cause of Sj"gren's syndrome. Our most recent studies of Id3 deficient mice indicate that 34 T cells play a role in this disease model. This novel finding is particularly interesting given that 34 T cells in Sj"gren's syndrome have been implicated in clinical case reports. We plan to use an Id3 conditional allele to investigate lineage and stage specific requirement of Id3 in disease development. Results from the proposed studies should establish a causal link between function of Id3 in specific cell lineage at specific stage of development and Sj"gren's syndrome. The involvement of 34 T cell in this disease model, if proves to be true, would be particularly novel and point to a new direction in clinical applications. RELEVANCE: This proposal is in response to the program announcement (PA-07-336) from National Center for Research Resources, which calls for Development of Animal Models and Related Biological Materials for Research. We plan to build a new animal model for studying Sj"gren's syndrome and make this model available for scientific community for relevant research. Sj"gren's syndrome is one of the most prevalent rheumatic autoimmune disease affecting approximately 4 million people in this country, mostly women reaching middle age. The disease is caused by chronic attack of the lachrymal and salivary glands by immune cells resulting in persistent dry eyes and mouth. Work carried out in my laboratory demonstrated that Id3 deficient mice develop primary Sj"gren's syndrome. However, the disease mechanism in this animal model is currently unknown. Our most recent work led to a new hypothesis that loss of Id3 in 34 T cells may be sufficient to initiate Sj"gren's syndrome. To test this hypothesis and to build a more defined animal model, we plan to create Id3 conditional knockout mouse which eliminates Id3 exclusively in 34 T cells. We will assess phenotypes relevant to Sj"gren's syndrome in this new animal model.