However, the hACE2Tg mouse model cannot fully explain: <b>1)</b> low expression of ACE2 observed in human lung and heart, but lung or heart failure occurs frequently in severe COVID-19 patients; <b>2)</b> low expression of ACE2 on immune cells, but lymphocytopenia occurs frequently in COVID-19 patients; and <b>3)</b> hACE2Tg mice do not mimic the natural course of SARS-CoV-2 infection in humans. The gene discussed is ACE2; the disease is COVID-19.