Knight Audrey C, Montgomery Stephanie A, Fletcher Craig A, Baxter Victoria K
Department of Pathology and Laboratory Medicine; Institute for Global Health and Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Department of Pathology and Laboratory Medicine; Division of Comparative Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Comp Med. 2021 Oct 1;71(5):383-397. doi: 10.30802/AALAS-CM-21-000031. Epub 2021 Oct 5.
Mice are an invaluable resource for studying virus-induced disease. They are a small, genetically modifiable animal for which a large arsenal of genetic and immunologic tools is available for evaluation of pathogenesis and potential vaccines and therapeutics. SARS-CoV-2, the betacoronavirus responsible for the COVID-19 pandemic, does not naturally replicate in wild-type mice, due to structural differences between human and mouse ACE2, the primary receptor for SARS-CoV-2 entry into cells. However, several mouse strains have been developed that allow for SARS-CoV-2 replication and clinical disease. Two broad strategies have primarily been deployed for developing mouse strains susceptible to COVID-19-like disease: adding in the human gene and adapting the virus to the mouse ACE2 receptor. Both approaches result in mice that develop several of the clinical and pathologic hallmarks of COVID-19, including acute respiratory distress syndrome and acute lung injury. In this review, we describe key acute pulmonary and extrapulmonary pathologic changes seen in COVID-19 patients that mouse models of SARS-CoV-2 infection ideally replicate, the essential development of mouse models for the study of Severe Acute Respiratory Syndrome and Middle Eastern Respiratory Syndrome and the basis of many of the models of COVID-19, and key clinical and pathologic features of currently available mouse models of SARS-CoV-2 infection.
小鼠是研究病毒诱导疾病的宝贵资源。它们是一种小型的、可进行基因改造的动物，有大量的基因和免疫工具可用于评估发病机制以及潜在的疫苗和治疗方法。导致 COVID-19 大流行的β冠状病毒 SARS-CoV-2，由于人类和小鼠 ACE2（SARS-CoV-2 进入细胞的主要受体）之间的结构差异，不会在野生型小鼠中自然复制。然而，已经培育出了几种允许 SARS-CoV-2 复制并引发临床疾病的小鼠品系。开发易患类 COVID-19 疾病小鼠品系主要采用了两种广泛的策略：添加人类基因以及使病毒适应小鼠 ACE2 受体。这两种方法都能使小鼠出现 COVID-19 的一些临床和病理特征，包括急性呼吸窘迫综合征和急性肺损伤。在这篇综述中，我们描述了 COVID-19 患者出现的关键急性肺部和肺外病理变化，理想情况下，SARS-CoV-2 感染小鼠模型能复制这些变化；还介绍了用于研究严重急性呼吸综合征和中东呼吸综合征的小鼠模型的重要发展情况以及许多 COVID-19 模型的基础；此外，还阐述了目前可用的 SARS-CoV-2 感染小鼠模型的关键临床和病理特征。
