Mice with F83Y/H353K mutations in the mouse ACE2 supported the infection of SARS-CoV-2, but the infected mice did not manifest symptoms; in addition, further conditional hybrid CMV-Cre derived Rosa26 hACE2 mice were generated, and these mice were more susceptible to the infection of SARS-CoV-2, with reduced body weight, survival rate, and obvious clinical symptoms. This evidence concerns the gene ACE2 and infection.