A transgenic model of ocular inflammation

描述（由申请人提供）：炎症性眼病是全球视力下降和失明的主要原因。 葡萄膜炎的动物模型相对较少，这限制了对疾病发病机制的理解。 没有生物学相关的系统筛选抗葡萄膜炎的药物活性。 现有的几种葡萄膜炎小鼠模型没有利用现代小鼠遗传学的新兴资源。 我们建议建立一个新的模型，葡萄膜炎疾病的转基因小鼠的基因工程表达特异性免疫原性蛋白质（来自眼部病原体）的特定子集的眼组织。 我们预测，这种转基因小鼠将发展眼部炎症性疾病时，这些病原体的挑战，也就是说，一个合成的葡萄膜炎模型可以产生的分子模拟。 本研究将优化酵母Gal 4-UAS反式激活系统用于哺乳动物细胞和转基因小鼠，并在酵母适应的lac-repressor系统中加入变阻器功能;建立眼组织特异性启动子控制下表达Gal 4转录激活因子的转基因小鼠和UAS上游识别序列控制下表达特异性蛋白的转基因小鼠;并分析这些小鼠品系的后代的自发性炎症以及用病原体和病原体蛋白免疫后的炎症。

DESCRIPTION (provided by applicant): Inflammatory eye disease is a major cause of decreased vision and blindness worldwide. Relatively few animal models of uveitis exist, which has limited understanding of disease pathogenesis. No biologically relevant system for screening of drugs active against uveitis is available. The few existing mouse models of uveitis do not take advantage of the burgeoning set of resources of modem mouse genetics. We propose creating a new model for uveitic disease by generating sets of transgenic mice engineered to express specific immunogenic proteins (derived from ocular pathogens) in specific subsets of ocular tissue. We predict that such transgenic mice will develop ocular inflammatory disease when challenged with those pathogens; that is, a synthetic uveitis model can be generated by molecular mimicry. This research will optimize the yeast Gal4-UAS transactivating system for use in mammalian cells and in transgenic mice, and add rheostat function with the mammalian-adapted lac-repressor system; create transgenic mice expressing the Gal4 transcriptional activator under the control of ocular tissue-specific promoters, and transgenic mice expressing specific proteins under the control of the UAS upstream recognition sequence; and analyze offspring of these mouse strains for spontaneous inflammation as well as inflammation following immunization with pathogen and pathogen protein.