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.

Stock No. 035041 K18-hACE2 ; Ifnar1^- is a multiple mutant strain assembled by breeding Stock Nos. 034860 and 028288. 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. 035041 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 Ifnar1^- targeted mutation may result in reduced immune response and increased susceptibility to SARS-CoV viral infection during clinical trials.

The K18-ACE2 transgene and Ifnar1^- targeted mutation are able to be maintained as homozygous in their individual mouse lines. Stock No. 035401 is viable and fertile as hemizygous K18-ACE2 and heterozygous Ifnar1^-. However, it is not yet known if Stock No. 035401 may be maintained as homozygous for both alleles [September 2020].
Of note, if homozygous null Ifnar1^- animals are maintained in low health barrier rooms, the use of medicated water (e.g., sulfatrim/trimethoprim-sulfa or enrofloxacin/Baytril) is suggested to increase overall colony health.