Please see the K18-hACE2 datasheet (Stock No. 034860) for important safety/handling and any updated information on K18-hACE2 mice in SARS-CoV-2 research.
Please note, 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.

Stock No. 034902 K18-hACE2 ; FcRn-/- hFcRn (32) Tg is a multiple mutant strain assembled by breeding Stock Nos. 034860 and 014565. In an attempt to offer popular alleles together, mouse lines may be bred together for purpose of researchers to study and characterize. It should be noted that the phenotype of Stock No. 034902 could vary from that originally described for the individual mouse lines used to assemble it. We may modify the strain description if necessary as published results become available. Each mutant allele is briefly described below [September 2020].

K18-hACE2 transgenic mice express the receptor for severe acute respiratory syndrome (SARS), caused by a coronavirus (SARS-CoV) in airway and other epithelia under control of the human keratin 18 (KRT18) promoter. Specifically, these mice contain 2.5 kb of the KRT18 genomic sequence, including the promoter, and the first intron (with a mutation in the 3' splice acceptor site to reduce exon skipping) and a translational enhancer (TE) sequence from alfalfa mosaic virus, upstream of the human angiotensin I converting enzyme (peptidyl-dipeptidase A) 2 coding sequence (hACE2), followed by exons 6-7 and the poly(A) signal of the human K18 gene. These elements have been found to be necessary for high-level expression and epithelial cell specificity of hACE2, the primary host cell receptor for SARS-CoV. In these mice, from founder line 2, K18-hACE2 transgene expression is evident in airway epithelial cells (but not in alveolar epithelia), as well as in epithelia of other internal organs, including the liver, kidney, and gastrointestinal tract. Recent research indicates that this line may also be useful in studies related to the study of 2019 novel coronavirus (SARS-CoV-2) pathogenesis.

Addition of the FcRn-/- targeted mutation and hFcRn (32) transgene may enhance the human-like protection of humanized IgG potentially making these mice a good model for developing antibody-based therapeutics against SARS-CoV, including assessing half-life, selecting efficacious variants, and determining dosage for clinical trials. Using this model, clinicians may be able to estimate the minimum antibody dose to achieve therapeutic serum concentrations, reducing the need for potentially risky dose-escalation treatments during clinical trials.

The K18-ACE2 transgene, FcRn-/- targeted mutation and hFcRn (32) transgene are able to be maintained as homozygous in their individual mouse lines. However, because the two transgenes are located ~1.9 Mbp apart on chromosome 2, it may be difficult to generate Stock No. 034902 mice with the two transgenes in cis (on the same chromosome). As such, The Jackson Laboratory will maintain and distribute as hemizygous for the K18-ACE2 transgene, hemizygous for the hFcRn (32) transgene and homozygous for the FcRn-/- targeted mutation.