Angiotensin-converting enzyme 2 (ACE2) is a member of the angiotensin-converting enzyme (ACE) family of dipeptidyl carboxypeptidases. ACE2 is expressed in a variety of human tissues and has a high affinity for angiotensin I (Ang I) and angiotensin II (Ang II) receptors. ACE2 catalyzes the cleavage of Ang I to angiotensin 1-9 (Ang 1-9) and Ang II to angiotensin 1-7 (Ang 1-7), which have vasodilatory and hypotensive effects ^[1]. ACE2 plays a role in regulating blood pressure, fluid balance, inflammation, cell proliferation, hypertrophy, and fibrosis, as well as in the regulation of cardiovascular and renal function and fertility ^[2]. ACE2 is also the common functional receptor for the spike protein of human coronaviruses HCoV-NL63, SARS-CoV, and SARS-CoV-2 ^[3]. However, due to species differences, the SARS-CoV-2 virus cannot bind to the ACE2 receptor of wild-type rodents ^[4-5]. Replacement of mouse Ace2 with human ACE2 by gene editing techniques resulted in humanized ACE2 mice (hACE2) that stably express human ACE2 receptors for COVID-19 studies.

This strain is a human ACE2 (hACE2) conditional overexpression model generated by integrating the hACE2 gene expression element into the mouse ROSA26 safe harbor site. Under normal conditions, the expression of hACE2 is blocked by the upstream loxP-Stop-loxP expression stop cassette. Upon mating with Cre mice, the Cre recombinase mediates the deletion of the sequence between the loxP sites, including the stop cassette, thereby enabling the expression of hACE2. When bred with tissue-specific Cre mice, overexpression of the hACE2 gene and protein can be achieved in specific tissues of the offspring mice. Homozygous ROSA26-LSL-hACE2 mice are viable and fertile.