ACE2 and infection: SARS-CoV-2 exhibits low infectivity to wild-type mice; therefore, to study the infectivity and spread of SARS-CoV-2 in this species, either mice must be engineered to express human ACE2, or SARS-CoV-2 virus must be mice-adapted.239,240 Currently, multiple engineered mouse models have been established to study SARS-CoV-2 invasion.240–244 SARS-CoV-2 can infect the olfactory epithelium of mice expressing human ACE2 (hACE2), and whether infection further progresses to the brain is likely dependent on promoter type, which controls hACE2 expression.