loxP-hACE2-CDStm Mouse

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 contains a loxP-hACE2 CDS-loxP gene expression cassette inserted at the endogenous mouse Ace2 gene locus, which enables the regulation of human ACE2 gene (hACE2) expression by the mouse endogenous Ace2 regulatory element. When bred with relevant tissue-specific Cre mouse mating, knockout of the hACE2 gene can be achieved in specific tissues of the offspring mice. Homozygous LoxP-hACE2-CDS^tm mice are viable and fertile.