Centre for Infection and Immunity Studies (CIIS), School of Medicine, Shenzhen Campus of Sun Yat-sen University, Guangdong, Shenzhen, China.
Department of Pathology, The International Peace Maternity & Child Health Hospital of China Welfare Institute (IPMCH), Shanghai Jiao Tong University, Shanghai, China.
J Med Virol. 2022 Aug;94(8):3605-3612. doi: 10.1002/jmv.27747. Epub 2022 Apr 13.
A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been identified as the causative agent of the current coronavirus disease 2019 pandemic. Development of animal models that parallel the clinical and pathologic features of disease are highly essential to understanding the pathogenesis of SARS-CoV-2 infection and the development of therapeutics and prophylactics. Several mouse models that express the human angiotensin converting enzyme 2 (hACE2) have been created, including transgenic and knock-in strains, and viral vector-mediated delivery of hACE2. However, the comparative pathology of these mouse models infected with SARS-CoV-2 are unknown. Here, we perform systematic comparisons of the mouse models including K18-hACE2 mice, KI-hACE2 mice, Ad5-hACE2 mice and CAG-hACE2 mice, which revealed differences in the distribution of lesions and the characteristics of pneumonia induced. Based on these observations, the hACE2 mouse models meet different needs of SARS-CoV-2 researches. The similarities or differences among the model-specific pathologies may help in better understanding the pathogenic process of SARS-CoV-2 infection and aiding in the development of effective medications and prophylactic treatments for SARS-CoV-2.
一种新型冠状病毒,严重急性呼吸系统综合征冠状病毒 2(SARS-CoV-2)已被确定为当前 2019 年冠状病毒病大流行的病原体。开发与疾病的临床和病理特征相平行的动物模型对于理解 SARS-CoV-2 感染的发病机制以及治疗和预防药物的开发非常重要。已经创建了几种表达人血管紧张素转换酶 2(hACE2)的小鼠模型,包括转基因和基因敲入品系,以及通过病毒载体介导的 hACE2 传递。然而,这些感染 SARS-CoV-2 的小鼠模型的比较病理学尚不清楚。在这里,我们对包括 K18-hACE2 小鼠、KI-hACE2 小鼠、Ad5-hACE2 小鼠和 CAG-hACE2 小鼠在内的小鼠模型进行了系统比较,这些模型揭示了感染 SARS-CoV-2 后病变的分布和肺炎特征的差异。基于这些观察结果,hACE2 小鼠模型满足了 SARS-CoV-2 研究的不同需求。特定于模型的病理学之间的相似性或差异可能有助于更好地理解 SARS-CoV-2 感染的发病机制,并有助于开发针对 SARS-CoV-2 的有效药物和预防治疗方法。