These mice express human ACE2, the receptor used by the severe acute respiratory syndrome coronavirus (SARS-CoV) to gain entry to cells. The human keratin 18 (KRT18) promoter directs expression to epithelia, including airway epithelial cells where infections typically begin. Recent research indicates the K18-hACE2 transgene may be useful in studying antiviral therapies for the 2019 novel coronavirus (SARS-CoV-2) pathogenesis and the disease outbreak COVID-19.
This strain also contains an Ifnar1- targeted mutation which may result in reduced immune response and increased susceptibility to SARS-CoV viral infection during clinical trials.
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.
Genetic Background | Generation |
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N1
|
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Null/Knockout) | Ifnar1 | interferon (alpha and beta) receptor 1 |
Allele Type |
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Transgenic (Inserted expressed sequence) |
Starting at:
$280.00 Domestic price for female 4-week |
485.00 Domestic price for breeder pair |
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.
The ~6.8 kb K18-hACE2 transgene was designed with, from 5' to 3', 2.5 kb of genomic sequence, including the promoter, and the first intron (with a mutation in the 3' splice acceptor site to reduce exon skipping) from the human keratin 18 (KRT18) gene, and a translational enhancer (TE) sequence from alfalfa mosaic virus. This was followed by the human angiotensin I converting enzyme (peptidyl-dipeptidase A) 2 (hACE2) coding sequence, and exons 6-7 and the poly(A) signal of the human K18 gene. This transgene was microinjected into fertilized (C57BL/6J x SJL/J)F2 oocytes. K18-hACE2 mice from founder line 2, with 8 copies of the transgene, were subsequently maintained by breeding transgenic mice with C57BL/6 mice for at least two generations (the genetic background of the mice sent to The Jackson Laboratory was later determined to be C57BL/6N via SNP testing). Upon arrival, three backcrosses to C57BL/6J (Stock No. 000664) were then performed to rederive, establish and expand a congenic colony at The Jackson Laboratory as Stock No. 034860. Some of these mice were bred to Ifnar1- mice (Stock No. 028288), carrying a knock-out mutation for the mouse Ifnar1 (interferon (alpha and beta) receptor 1) gene, to create this new strain as Stock No. 035041.
In May 2020, analysis commissioned by The Jackson Laboratory determined that multiple copies of the Tg(K18-ACE2)2Prlmn transgene integrated at a single site on chromosome 2 (99,209,508-99,220,724; mouse mm10). An ~11 kb duplication of the host genome (chr2:99,209,508-99,220,724) is present at both ends of the integrated transgene array. Currently, there are no genes annotated in this region. The transgene copy number of the hemizygous mouse is estimated to be 8 full copies (or 12-30 partial copies).
Allele Name | targeted mutation 1.2, Edward E Schmidt |
---|---|
Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | |
Gene Symbol and Name | Ifnar1, interferon (alpha and beta) receptor 1 |
Gene Synonym(s) | |
Strain of Origin | (C57BL/6 x 129S6/SvEvTac)F1 |
Chromosome | 16 |
Molecular Note | The targeting vector was designed to insert a self-excising FRT-Prm1pFlppol2Neo-FRT cassette and loxP site in intron 2, and a second loxP site in intron 3 of the gene. Facilitated self-excision of the cassette in the male germline and resulted in offspring with one FRT site and loxP site upstream of exon 3, and a second loxP site downstream of exon 3. Cre-mediated recombination removed the floxed neo cassette and exon 3. The resulting non-functional protein contains an exon 2-4 splice variant and frameshift leading to translation of 11 arbitrary (missense) amino acids within the N-terminal extracellular domain followed by a stop codon. |
Allele Name | transgene insertion 2, Stanley Perlman |
---|---|
Allele Type | Transgenic (Inserted expressed sequence) |
Allele Synonym(s) | K18-hACE2 |
Gene Symbol and Name | Tg(K18-ACE2)2Prlmn, transgene insertion 2, Stanley Perlman |
Gene Synonym(s) | |
Strain of Origin | (C57BL/6J x SJL/J)F2 |
Chromosome | 2 |
Molecular Note | The ~6.8 kb transgene was designed with, from 5' to 3', 2.5 kb of genomic sequence, including the promoter, and the first intron (with a mutation in the 3' splice acceptor site to reduce exon skipping) from the human K18 gene, and a translational enhancer (TE) sequence from alfalfa mosaic virus. This was followed by the human angiotensin I converting enzyme (peptidyl-dipeptidase A) 2 (hACE2) coding sequence, and exons 6-7 and the poly(A) signal of the human K18 gene. The transgene integrated at a single site on chromosome 2 (99,209,508-99,220,724; mouse mm10). An ~11 kb duplication of the host genome (chr2:99,209,508-99,220,724) is present at both ends of the integrated transgene array. Currently, there are no genes annotated in this region. The transgene copy number of the hemizygous mouse is estimated to be 8 full copies (or 12-30 partial copies). 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. |
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.
When using the K18-hACE2 ; Ifnar1- mouse strain in a publication, please cite the originating article(s) and include JAX stock #035041 in your Materials and Methods section.
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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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