HFH4-hACE2 is a transgenic mouse line that has FoxJ1 promoter driven human ACE2 (hACE2) over-expression. This model organism was designed in an attempt to overcome the issue of SARS-CoV-2 S protein not efficiently binding to murine ACE2. hACE2 was found to be expressed in ciliated epithelial cells in the respiratory tract as well as in central nervous system tissue. When infected with SARS-CoV-2, the following key results were observed:

• mice lost minimal weight, but only 60% were alive 5 days post infection (dpi)
• SARS-CoV-2 virus could be detected in the lung 2 dpi
• death is presumably caused by viral invasion of the brain
• whole body plethysmography (WBP) reveals that respiratory infection is not the likely cause of death

These findings suggest that HFH4-hACE2 mice are not an accurate model for COVID-19 pathogenesis.