Nomenclature: MGI:1917258

• ARDS is a serious complication of COVID-19 and present in a large percentage of COVID-19 deaths. ACE2 is protective against ARDS.
• Binding of viral spike SARS protein to ACE2 in mice downregulates ACE2 expression. Loss of ACE2 expression is associated with severe lung failure. Ace2 knockout mice have been used in ARDS and SARS research.
• This model does NOT carry the human ACE2 gene and thus is likely not permissive for infection by clinical isolates of SARS-CoV-2. Taconic has mice that express human ACE2 (hACE2) available now. Learn more about hACE2 mice for COVID-19 research and mouse-adapted SARS-CoV-2 viruses.
• The Ensembl database shows two isoforms of mouse ACE2 protein, one starting from Exon 2 of the gene (805 aa) and the second starting from Exon 6 (521 aa). The modification in this model targets the second exon (first coding exon) of Ace2, which is expected to result in a loss-of-function allele for the full-length isoform. It is unknown whether the second isoform will be produced in this model and if produced whether it is functional or not and can compensate for the loss of the full-length isoform. Correct targeting of the allele was confirmed by Southern blot analysis. Several publications have described phenotypic differences between wild type and homozygous mutant animals for this modification, consistent with interference with Ace2 function. It is recommended that researchers confirm loss-of-function status of the allele in their experimental system or tissue of interest.
• This line was generated on a mixed genetic background (B6;129S5). Researchers should be aware that phenotypes such as hypertension may vary for specific Ace2 knockout alleles on different inbred genetic backgrounds (Gurley and Coffman, 2007). Thus, as the result of a mixed genetic background the Ace2 knockout mice may show considerable inter-animal variation in phenotypes. It is recommended to carefully consider the impact of the genetic background when planning and interpreting experiments. Taconic can advise on backcross strategies and provide testing for marker-assisted speed congenic breeding. Generation of a fully congenic line can take 12-18 months.
• The murine Ace2 gene is located on the X chromosome. Female knockouts are homozygous (ko/ko). Male knockouts are hemizygous (ko/y).