Generation of IL-33 Deficient Mice

描述（由申请方提供）：本项目的目的是产生IL-33缺陷小鼠并对其进行初步表征。IL-33是最近鉴定的白细胞介素-1家族的成员，其包括IL-1-α、IL-1-β和IL-18。2005年11月，IL-33被鉴定为白细胞介素-1受体家族成员ST 2（正式名称IL 1 RL 1）的细胞外配体。关于IL- 33的迅速扩展的文献表明，作为ST 2受体的细胞外配体，IL-33在变态反应和免疫疾病中具有有效的免疫调节功能。IL-33与2003年发现的称为高内皮小静脉核因子（NF-HEV）的分子相同，NF-HEV是一种在内皮中高度表达的具有转录阻遏物性质的核因子。内源性核IL-33在内皮细胞和上皮细胞中表达，代表慢性炎症中IL-33调节的附加模式。在IL-33被鉴定为ST 2受体的配体之前，ST 2受体在临床和实验研究中与炎性哮喘、肺纤维化、血管疾病、败血症和心脏病相关。虽然目前可获得ST 2受体敲除小鼠，但其不能解决IL-33在骨髓祖细胞流出和扩增、IL-33/ST 2L信号传导的调节以及IL-33在慢性炎症调节中的核功能中的作用。基于ST 2受体敲除小鼠的生存能力，我们预期IL-33敲除小鼠将是存活的。IL-33基因敲除小鼠，这是目前还没有，有很大的潜力，以确定新的调节机制，在人类慢性炎症性疾病。 公共卫生相关性：项目叙述本项目的目的是产生IL-33缺陷小鼠。IL-33是白细胞介素-1家族的成员，最近被鉴定为白细胞介素-1受体家族成员ST 2的细胞外配体。关于IL-33的迅速扩展的文献表明，作为ST 2受体的细胞外配体，IL-33在变态反应和免疫疾病中具有有效的免疫调节功能。IL-33基因敲除小鼠，目前还没有，具有很高的潜力，以确定新的调节机制，在人类肺部和慢性炎症性疾病。

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.