The research community is in a race to understand the molecular mechanisms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, to repurpose currently available antiviral drugs and to develop new therapies and vaccines against coronavirus disease 2019 (COVID-19). One major challenge in achieving these goals is the paucity of suitable preclinical animal models. Mice constitute ~70% of all the laboratory animal species used in biomedical research. Unfortunately, SARS-CoV-2 infects mice only if they have been genetically modified to express human ACE2. The inherent resistance of wild-type mice to SARS-CoV-2, combined with a wealth of genetic tools that are available only for modifying mice, offers a unique opportunity to create a versatile set of genetically engineered mouse models useful for COVID-19 research. We propose three broad categories of these models and more than two dozen designs that may be useful for SARS-CoV-2 research and for fighting COVID-19.

研究界正在竞相了解严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 感染的分子机制，重新利用现有的抗病毒药物，并开发针对 2019 年冠状病毒病 (COVID-19) 的新疗法和疫苗。实现这些目标的一个主要挑战是缺乏合适的临床前动物模型。小鼠约占生物医学研究中使用的所有实验动物物种的 70%。不幸的是，只有经过基因改造以表达人类 ACE2 的小鼠，SARS-CoV-2 才会感染它们。野生型小鼠对 SARS-CoV-2 的固有抵抗力，加上仅可用于修饰小鼠的大量遗传工具，为创建可用于 COVID-19 研究的多功能基因工程小鼠模型提供了独特的机会。我们提出了这些模型的三大类和两打以上的设计，这些设计可能对 SARS-CoV-2 研究和对抗 COVID-19 有用。