Angiotensin-converting enzyme 2 (ACE2) is the predominant cell surface receptor for SARS-CoV-2 virus infection in humans, but due to species differences, the SARS-CoV-2 virus is unable to bind to the ACE2 receptor in most wild-type rodents. By inserting the "K18 promoter-human ACE2 CDS-P2A-CreERT2-rBGpA" sequence into the safety harbor of the mouse genome through gene editing technology, humanized ACE2 mice (K18-hACE2) that stably express the human ACE2 receptor can be obtained. This mouse model expresses human ACE2 protein in epithelial cells under the regulation of the human keratin K18 promoter, including the most initially infected airway epithelial cells. This model also carries the CreERT2 element, which can be induced by tamoxifen to express the Cre recombinase, so this strain can be used either alone for COVID-19 and related studies or in combination with flox mice for studying the role of specific host genes in response to SARS-CoV-2 virus infection.

K18-hACE2 mice can be infected with the SARS-CoV-2 virus, resulting in severe disease characterized by weight loss, rapid respiration, hunched posture, and immobility. This strain responds to viral attack in a dose-dependent manner, thus allowing the study of severe acute respiratory disease in mice heavily infected by high doses of the virus, as well as the long-term effects of low doses of mild infection.

The model should be handled in strict accordance with the guidelines for the prevention of SARS-CoV-2 virus infection in humans as specified by CDC, ABSA, and WHO, and appropriate personal protective equipment (PPE) and handling methods should always be used when using these mice for research.