ACE2-GR mice have the human ACE2 gene replacing the endogenous mouse Ace2 sequences. Expression is directed by the human ACE2 regulatory elements. Human ACE2 is the receptor used for cellular entry by several coronaviruses, including severe acute respiratory syndrome coronavirus-1 (SARS-CoV) and -2 (SARS-CoV-2). Because cells expressing human ACE2 are susceptible to SARS-CoV-2, these mice may be useful for studying antiviral therapies to COVID-19.
These mice should be handled in a manner consistent with CDC/ABSA/WHO guidelines for prevention of human infection with the SARS-CoV-2 virus. Proper PPE and handling methods should be used at all times when working with these mice. Additional important guidelines for using SARS-CoV-2 susceptible mouse lines.
Of note, hACE2-KI (Stock No. 035000) has some similarities to this strain, yet have floxed human ACE2 cDNA replacing the endogenous sequence. Also available are K18-hACE2 transgenic mice with human ACE2 expression directed to epithelia (Stock No. 034860).
Michael Koob, University of Minnesota
ACE2-GR mice have the human ACE2 gene replacing the endogenous mouse Ace2 sequences on the X Chromosome. These mice express human ACE2 in place of mouse Ace2, as directed by regulatory elements of the human ACE2 gene.
Human ACE2 is the receptor used for cellular entry by several coronaviruses, including severe acute respiratory syndrome coronavirus-1 (SARS-CoV), severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2; 2019 novel coronavirus) and HCoV-NL63. This ACE2-GR mouse model may be useful in studying antiviral therapies for these coronaviruses, particularly SARS-CoV-2 pathogenesis and the disease outbreak COVID-19.
Hemizygous males and homozygous females are viable and fertile.
Of note, hACE2-KI (Stock No. 035000) mice have some similarities to this strain, yet contain loxP sites flanking human ACE2 cDNA which replaces the endogenous Ace2 sequence.
The ACE2-GR allele has the entire X-linked angiotensin I converting enzyme (peptidyl-dipeptidase A) 2 gene [Ace2] replaced with the entire human ACE2 gene. First, a targeting vector was designed to replace 71 kb (70,987bp) on the mouse X chromosome stretching from, but not including, collectrin, amino acid transport regulator (Cltrn) gene to BMX non-receptor tyrosine kinase (Bmx) gene with a syntenic 66 kb (65,812bp) region from the human X chromosome. A loxN-flanked neomycin resistance (neo) cassette was inserted at the junction between the human ACE2 and mouse Bmx genes. The construct was electroporated into C57BL/6NTac-derived PRX-B6N embryonic stem (ES) cells. Correctly targeted ES cells were transiently transfected with a cre expression plasmid to delete the neo cassette. Resulting ES cells were injected into recipient blastocysts. Chimeric mice were bred to albino C57BL/6J mice (Stock No. 000058). Female mice were sent to The Jackson Laboratory Repository in 2020. Upon arrival, oocytes from these females were used with C57BL/6J sperm for IVF to generate a colony. Subsequently, the Tyrc-2J albino gene was bred out of the colony.
Currently there are no related genes or alleles for this strain.
Ace2 is X-linked. Hemizygous males and homozygous females are viable and fertile.
When using the ACE2-GR mouse strain in a publication, please cite the originating article(s) and include JAX stock #035800 in your Materials and Methods section.