Generation of IL-33 Deficient Mice

IL-33 缺陷小鼠的产生

• 批准号: 7963648
• 负责人: KATYA RAVID
• 金额: $ 8.13万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-19 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7963648
• 关键词: Address; Affect; Allergic; Asthma; Backcrossings; Bone Marrow; Chronic; Clinical; Disease; Embryo; Endothelium; Epithelial Cells; Family; Family member; Generations; Heart Diseases; High Endothelial Venule; Human; Hypersensitivity; Immune System Diseases; Immunity; Inflammation; Inflammatory; Interleukin-1; Interleukin-1 Receptors; Interleukin-1 alpha; Interleukin-1 beta; Interleukin-18; Knock-out; Knockout Mice; Lead; Ligands; Literature; Lung; Mus; Names; Nuclear; Property; Pulmonary Fibrosis; Regulation; Research Personnel; Role; Sepsis; Sequence Alignment; Signal Transduction; Staging; Stem cells; System; Tissues; Transcription Repressor/Corepressor; Vascular Diseases; base; extracellular; member; mouse model; novel; public health relevance; receptor; research study; tool

DESCRIPTION (provided by applicant): The objective of this project is to generate IL-33 deficient mice and to subject them to initial characterization. IL-33 is a recently identified member of the interleukin-1 family, which includes IL-1- alpha, IL-1-beta and IL-18. In November 2005, IL-33 was identified as the extracellular ligand for an interleukin-1 receptor family member, ST2 (official name IL1RL1). The rapidly expanding literature on IL- 33 shows that as an extracellular ligand for the ST2 receptor, IL-33 has potent immunomodulary functions in allergy and immune diseases. IL-33 is identical to a molecule discovered in 2003 called Nuclear Factor of High Endothelial Venules (NF-HEV), a nuclear factor highly expressed in the endothelium with transcriptional repressor properties. Endogenous nuclear IL-33 is expressed in endothelial and epithelial cells representing an addition mode of IL-33 regulation in chronic inflammation. Prior to the identification of IL-33 as the ligand for the ST2 receptor, the ST2 receptor had been associated with inflammatory asthma, pulmonary fibrosis, vascular diseases, sepsis and heart disease in clinical and experimental studies. While an ST2 receptor knockout mouse is currently available, it cannot address the roles of IL-33 in bone marrow progenitor cell egress and expansion, regulation of IL-33/ST2L signaling, and nuclear functions of IL-33 in the regulation of chronic inflammation. Based on the viability of ST2 receptor knockout mice, we anticipate that IL-33 knockout mice will be viable. An IL-33 knockout mouse, which is currently not available, has a high potential to identify novel regulatory mechanisms in human chronic inflammatory diseases. PUBLIC HEALTH RELEVANCE: PROJECT NARRATIVE The objective of this project is to generate IL-33 deficient mice. IL-33 is a member of the interleukin-1 family that was recently identified as the extracellular ligand for an interleukin-1 receptor family member, ST2. The rapidly expanding literature on IL-33 shows that as an extracellular ligand for the ST2 receptor, IL-33 has potent immunomodulary functions in allergy and immune diseases. An IL-33 knockout mouse, which is currently not available, has a high potential to identify novel regulatory mechanisms in human pulmonary and chronic inflammatory diseases.

描述（由申请人提供）：该项目的目的是生成IL-33不足的小鼠，并使它们具有初始特征。 IL-33是白介素-1家族的最近确定的成员，其中包括IL-1-Alpha，IL-1-β和IL-18。 2005年11月，IL-33被确定为白介素-1受体家族成员ST2（官方名称IL1RL1）的细胞外配体。 IL-33上快速扩展的文献表明，作为ST2受体的细胞外配体，IL-33在过敏和免疫疾病中具有有效的免疫调节功能。 IL-33与2003年发现的分子相同，称为高内皮静脉（NF-HEV）的核因子，这是一种在内皮中高度表达具有转录抑制剂特性的核因子。内源性核IL-33在代表慢性炎症中IL-33调控的加法模式的内皮和上皮细胞中表达。在将IL-33鉴定为ST2受体的配体之前，在临床和实验研究中，ST2受体与炎症性哮喘，肺纤维化，血管疾病，败血症和心脏病有关。虽然目前有ST2受体敲除小鼠，但它无法解决IL-33在骨髓祖细胞出口中的作用和扩张，IL-33/ST2L信号的调节以及IL-33在慢性炎症调节中的核功能。基于ST2受体基因敲除小鼠的生存能力，我们预计IL-33敲除小鼠将是可行的。目前尚不可用的IL-33敲除小鼠具有识别人类慢性炎症性疾病中新型调节机制的高潜力。 公共卫生相关性：项目叙事该项目的目的是产生IL-33不足的小鼠。 IL-33是白介素-1家族的成员，最近被确定为白介素-1受体家族成员ST2的细胞外配体。 IL-33上快速扩展的文献表明，作为ST2受体的细胞外配体，IL-33在过敏和免疫疾病中具有有效的免疫调节功能。目前尚不可用的IL-33敲除小鼠具有识别人类肺部和慢性炎症性疾病中新型调节机制的高潜力。