Transgenic Mouse Model for the Common Cold

普通感冒转基因小鼠模型

基本信息

批准号：
7545868
负责人：
Matthias Gromeier
金额：
$ 23.4万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-01-01 至 2010-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7545868
关键词：
Acute Acute respiratory infection Age Animal Model Antiviral Agents Asthma Benign Characteristics Chronic Obstructive Airway Disease Common Cold Consultations Coxsackie Viruses Development Disease model Enterovirus Epithelial Cells Exhibits Family Picornaviridae Genes Health Expenditures Healthcare Human Immune response Individual Infection Intercellular adhesion molecule 1 Lesion Life Lung Lung diseases Modeling Morbidity - disease rate Mus Pathogenesis Patients Physicians Primates Public Health Receptor Cell Research Respiratory System Respiratory Tract Infections Respiratory tract structure Risk Seasons Structure of respiratory epithelium Testing Transgenic Mice Tropism Viral Viral Respiratory Tract Infection chemotherapy drug development improved mouse model novel therapeutic intervention prevent receptor respiratory volunteer

项目摘要

DESCRIPTION (provided by applicant): Viral respiratory tract infections are the most common cause of acute morbidity in individuals of all ages worldwide. Picornaviruses alone are responsible for ~80% of all acute respiratory infections during peak season and are a major cause for restricted activity and physician consultation. Despite the generally benign course of the common cold caused by picornaviruses, it is the main culprit for acute exacerbation of serious respiratory system disorders, for example bronchial asthma or chronic obstructive pulmonary disease. The mechanisms of primary picornaviral respiratory tract infection or secondary exacerbation of pulmonary disease are not fully understood. Moreover, no specific anti-viral chemotherapy is available. A major impediment to advances in research of pathogenic mechanisms and anti-viral drug development is the absence of a practical animal model for the common cold. Generally, studies of pathogenesis and pharmacologic testing rely on deliberate infection of volunteers. We generated mice transgenic for the human intercellular adhesion molecule-1 (hICAM-1) gene, which exhibit hICAM-1 expression in respiratory epithelium similar to humans. These mice in principle are susceptible to infection with the vast majority of picornaviruses, which recognize hICAM-1 as a cellular receptor. This project aims to establish a murine model for the common cold by generating picornaviruses with respiratory tropism capable of propagating and eliciting characteristic lesions and host responses in the respiratory tract of hICAM-1 transgenic mice. Our research intends to generate a practical small animal model for the common cold, a major cause for pulmonary illness and associated health care expenditure worldwide. This disease model would provide far improved opportunities to unravel mechanisms of viral respiratory tract infection and to test new therapeutic approaches benefiting patients at risk from exacerbation of underlying pulmonary disease.

描述（由申请人提供）：病毒性呼吸道感染是全世界所有年龄段个体急性发病的最常见原因。仅小核糖核酸病毒就导致旺季约 80% 的急性呼吸道感染，也是限制活动和医生咨询的主要原因。尽管小核糖核酸病毒引起的普通感冒病程通常是良性的，但它是严重呼吸系统疾病（例如支气管哮喘或慢性阻塞性肺病）急性恶化的罪魁祸首。原发性小核糖核酸病毒呼吸道感染或肺部疾病继发性恶化的机制尚不完全清楚。此外，尚无特异性抗病毒化疗方案。致病机制研究和抗病毒药物开发进展的一个主要障碍是缺乏针对普通感冒的实用动物模型。一般来说，发病机制和药理学测试的研究依赖于志愿者的故意感染。我们培育了人类细胞间粘附分子 1 (hICAM-1) 基因转基因小鼠，其呼吸道上皮细胞中的 hICAM-1 表达与人类相似。这些小鼠原则上容易受到绝大多数小核糖核酸病毒的感染，这些病毒将 hICAM-1 识别为细胞受体。该项目旨在通过产生具有呼吸道趋向性的小核糖核酸病毒，能够在 hICAM-1 转基因小鼠的呼吸道中传播并引起特征性病变和宿主反应，建立普通感冒的小鼠模型。我们的研究旨在为普通感冒建立实用的小动物模型，普通感冒是全球肺部疾病和相关医疗保健支出的主要原因。这种疾病模型将为揭示病毒性呼吸道感染的机制和测试新的治疗方法提供更好的机会，使面临潜在肺部疾病恶化风险的患者受益。

项目成果

期刊论文数量（1）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Adaptation of an ICAM-1-tropic enterovirus to the mouse respiratory tract.

ICAM-1 嗜性肠道病毒对小鼠呼吸道的适应。

DOI：
10.1128/jvi.01502-10
发表时间：
2011
期刊：
Journal of virology
影响因子：
5.4
作者：
Wang,EricS;Dobrikova,Elena;Goetz,Christian;Dufresne,AndrewT;Gromeier,Matthias
通讯作者：
Gromeier,Matthias