Please note, these mice should be handled in a manner consistent with CDC/ABSA/WHO guidelines for prevention of human infection with the SARS-CoV-2 virus. Proper PPE and handling methods should be used at all times when working with these mice. Additional important guidelines for using SARS-CoV-2 susceptible mouse lines.

hACE2-KI mice have a loxP-flanked human ACE2 cDNA sequence replacing the endogenous mouse Ace2 sequences on the X Chromosome. These mice express human ACE2 in place of mouse Ace2, as directed by endogenous regulatory elements of the mouse Ace2 locus. Homozygous females and hemizygous males are viable and fertile.

Human ACE2 is the receptor used for cellular entry by several coronaviruses, including severe acute respiratory syndrome coronavirus-1 (SARS-CoV), severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2; 2019 novel coronavirus) and HCoV-NL63. This hACE2-KI mouse model may be useful in studying antiviral therapies for these coronaviruses, particularly SARS-CoV-2 pathogenesis and the disease outbreak COVID-19.

The donating investigator reports that initial studies with 10-13 week old hACE2-KI heterozygous females are susceptible to SARS-CoV-2, and the virus replicates efficiently in respiratory tissues. Specifically, heterozygous females were infected intranasally with wildtype SARS-CoV-2 variants [a 1:1 ratio of SARS-CoV-2(S-614D) and SARS-CoV-2(S-614G), using 1x10^5 plaque forming units of each variant] and samples were collected at days 2-4 post-infection. This revealed high viral RNA loads in the nasal conchae and lungs. Virus RNA was also detected in olfactory bulbs and at lower levels in brain tissues. Low to undetectable levels of virus were observed in spleen, small intestine, kidneys and feces. Heterozygous females did not exhibit morbidity or mortality (e.g., no weight loss) when infected with typical wildtype SARS-CoV-2 viruses. [Zhou et al. 2021 Nature 592:122]
We will update this description as more information becomes available.

These hACE2-KI mice (Stock No. 035000) have loxP sites flanking the human ACE2 cDNA sequence. Upon exposure to Cre recombinase, the human ACE2 cDNA will be deleted - generating a knock-out allele.
Of note, ACE2-GR (Stock No. 035800) has some similarities, but differs in that it has the human ACE2 coding and regulatory/non-coding sequences replacing the endogenous mouse Ace2 coding and regulatory/non-coding sequences, and it does not have the loxP sites.