Animal Core

动物核心

• 批准号: 7790043
• 负责人: LEE Mark WETZLER
• 金额: $ 28.99万
• 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: 2010-08-01 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7790043
• 关键词: Acute; Acute Pneumonia; Animals; ApoE knockout mouse; Apolipoprotein E; Arterial Fatty Streak; Atherosclerosis; Bacterial Infections; Blood; Blood Platelets; Blood specimen; Bone Marrow; Bone Marrow Transplantation; Breeding; Cells; Chlamydophila pneumoniae; Chronic; Collecting Cell; Communities; Development; Endothelial Cells; Foam Cells; Gene Deletion; Goals; IL1R1 gene; Image; Immune; Immune response; In Vitro; Infection; Inflammation; Inflammatory; Inflammatory Response; Interleukin-1; Interleukin-1 Receptors; Knock-out; Knockout Mice; Letters; Lipids; Magnetic Resonance Imaging; Megakaryocytes; Mouse Strains; Mus; Natural Immunity; Oral; Pneumonia; Porphyromonas gingivalis; Research; Research Project Grants; Robin bird; Role; Signal Pathway; Signal Transduction; Specificity; TLR2 gene; Tissues; Transgenic Mice; atherothrombosis; bone loss; in vivo; macrophage; mouse model; novel; osteoclastogenesis; pathogen; programs; receptor expression; response

The purpose of the Animal Core of this Program Project is to support the four research projects by maintaining and breeding mice, collecting cells, tissues and blood from mice, performing bacterial infection with Porphyromonas gingivalis and Chlamydia pneumoniae, and performing in vivo imaging studies by MRI / MRA. To define cell specificity of IL-lp signaling in the development of inflammatory atherosclerotic plaque, the Animal Core will perform bone marrow transplantation to produce bone marrow chimeric mice in which either the donor cells or the recipient mice are IL-1p KO, and challenge these mice with C. pneumoniae or P. gingivalis. The Animal Core will generate two novel transgenic mice, in which TLR2 or IL-1 receptor (IL- 1R) expression is targeted specifically to endothelial cells. These mice will be used to examine endothelial cell TLR2 or IL-IR signaling in inflammatory responses to P. gingivalis and C. pneumoniae infection. We currently maintain some of these KO mice in our mouse colony, including the ApoE, TLR2, IL-1 R single KO mice as well as ApoE/TLR2 double KO mice. We will obtain IL-ip, LXRa, LXRp single KO mice, and LXRa/p double KO mice.We will cross KO mice to generate double KO mice: ApoE x LXRa, ApoE x LXRp, ApoE X IL-IR, and ApoE x IL-1 p. To support the four Projects of the Program, we propose the following Aims for the Animal Core: AIM 1. Maintain and breed knockout mouse lines. AIM 2.Obtain cell, tissue and blood samples from mice for analysis by each project. AIM 3. Perform infection of P. gingivalis or C. pneumoniae, generate bone marrow chimeric mice by bone marrow transplantation, and perform MRI / MRA for each project. AIM 4.Construct novel transgenic mice strains in which TLR2 or IL-IR expression is targeted to endothelial cells. RELEVANCE

本计划项目的动物核心的目的是支持四个研究项目， 小鼠的饲养繁殖，收集小鼠的细胞、组织和血液，进行细菌感染， 牙龈卟啉单胞菌和肺炎衣原体，并通过MRI /MRI进行体内成像研究。 MRA。为了确定炎性动脉粥样硬化斑块发展中IL-1 p信号传导的细胞特异性， 动物中心将进行骨髓移植以产生骨髓嵌合小鼠，其中 无论是供体细胞还是受体小鼠都是IL-1 β KO，并用C.肺炎或 P.牙龈炎动物中心将产生两个新的转基因小鼠，其中TLR 2或IL-1受体（IL-1 R） 1 R）表达特异性靶向内皮细胞。这些小鼠将用于检查内皮细胞 细胞TLR 2或IL-1 R信号转导对牙龈卟啉单胞菌和C.肺炎感染。我们 目前在我们的小鼠群体中保留了一些这些KO小鼠，包括ApoE、TLR 2、IL-1 R单KO 小鼠以及ApoE/TLR 2双KO小鼠。我们将获得IL-1 β、LXR α、LXR β单基因敲除小鼠， 我们将杂交KO小鼠以产生双KO小鼠：ApoE x LXRa，ApoE x LXRp， ApoE X IL-1 p和ApoE X IL-1 R。为了支持该计划的四个项目，我们提出了以下目标 动物核心：AIM 1。保持和繁殖敲除小鼠品系。目的2.获取细胞、组织和血液 每个项目从小鼠身上采集样本进行分析。AIM 3.进行牙龈卟啉单胞菌或C.肺炎， 通过骨髓移植产生骨髓嵌合体小鼠，并对每个小鼠进行MRI / MRA， 项目目的4.构建靶向表达TLR 2或IL-1 R的新型转基因小鼠品系， 内皮细胞 相关性