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A model to study human TLR9 function in mice

研究人类 TLR9 功能的小鼠模型

基本信息

批准号：
7738989
负责人：
Gregory M Barton
金额：
$ 18.28万
依托单位：
UNIVERSITY OF CALIFORNIA BERKELEY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-06-05 至 2011-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7738989
关键词：
Address Adenoviruses Affect Animal Model Antigen-Presenting Cells Antiviral Agents Area Asthma Autoimmune Diseases B-Lymphocytes Backcrossings Biology Cells Clinical Communicable Diseases CpG dinucleotide DNA DNA Viruses Dendritic Cells Engineering Family Genome Genomics Goals Herpesviridae Human Hypersensitivity Immune Immune response Immunity Immunization Individual Injection of therapeutic agent Ligands Listeriosis Lupus Measures Modeling Mouse Strains Mus Nucleic Acids Outcome Papillomavirus Pattern Play RNA Viruses Research Research Project Grants Resistance Role Scheme Specificity Symptoms TLR9 gene Testing Therapeutic Toll-like receptors Transgenes Transgenic Mice Transgenic Organisms Vaccine Design Vaccines Viral base clinically relevant cytokine interest macrophage member mouse toll-like receptor 9 nonhuman primate preference promoter public health relevance receptor species difference

项目摘要

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.

描述（由申请人提供）：本研究计划的总体目标是了解人类和小鼠 Toll 样受体 9 (TLR9) 之间差异的重要性。 TLR9 的特异性及其在免疫细胞中的表达在这些物种之间存在差异，因此很难将 TLR9 功能的小鼠研究扩展到人类。在该提案中，人TLR9转基因盒将用于创建表达人TLR9的小鼠品系或具有人表达模式的小鼠TLR9。这些小鼠中 TLR9 的功能将使用多种标准进行评估。公共健康相关性：使用 Toll 样受体 9 (TLR9) 的合成配体治疗传染病、生产更好的疫苗以及缓解过敏或哮喘症状具有相当大的临床兴趣。不幸的是，人类和小鼠中 TLR9 功能的差异使得很难评估此类方法在非人类灵长类动物以外的动物模型中的功效。该提案的重点是创建和表征“人源化”TLR9 小鼠，以便能够比较人类和小鼠之间的 TLR9 功能。