A model to study human TLR9 function in mice

描述（由申请人提供）：本研究计划的总体目标是了解人和小鼠toll样受体9 （TLR9）差异的意义。TLR9的特异性及其在免疫细胞中的表达在这些物种之间都存在差异，这使得TLR9功能的小鼠研究难以扩展到人类。本课题将利用人TLR9转基因盒构建表达人TLR9的小鼠品系或具有人表达模式的小鼠TLR9。TLR9在这些小鼠中的功能将使用一些标准进行评估。公共卫生相关性：使用toll样受体9 （TLR9）的合成配体来治疗传染病、生产更好的疫苗和缓解过敏或哮喘症状有相当大的临床兴趣。不幸的是，人类和小鼠中TLR9功能的差异使得除了非人类灵长类动物之外，很难评估这种方法在动物模型中的有效性。本提案的重点是创建和表征“人源化”TLR9小鼠，以便比较人和小鼠之间的TLR9功能。

DESCRIPTION (provided by applicant): The overall goal of this research plan is to understand the significance of differences between human and mouse Toll-like receptor 9 (TLR9). Both the specificity of TLR9 and its expression among immune cells differ between these species, making it difficult to extend mouse studies of TLR9 function into humans. In this proposal, a human TLR9 transgenic cassette will be used to create mouse strains expressing human TLR9 or mouse TLR9 with the human expression pattern. The function of TLR9 in these mice will be evaluated using a number of criteria. PUBLIC HEALTH RELEVANCE: There is considerable clinical interest in using synthetic ligands of Toll-like receptor 9 (TLR9) to treat infectious disease, generate better vaccines, and alleviate symptoms of allergy or asthma. Unfortunately, differences in the function of TLR9 in humans and mice have made it difficult to assess the efficacy of such approaches in animal models other than non-human primates. This proposal focuses on creating and characterizing "humanized" TLR9 mice that will enable the comparison of TLR9 function between humans and mice.