To demonstrate the utility of our RG-rescued SARS-CoV-2 viruses in recapitulating SARS-CoV-2 replication and dissemination in vivo and the immunopathogenesis associated with infection, we used the human angiotensin-converting enzyme 2 (hACE2)-K18 transgenic mouse model, which expresses hACE2 driven by the keratin 18 (K18) promoter. This evidence concerns the gene ACE2 and infection.