Also known as: RAB/6N, RAB6N
Also known as: RAB/6N, RAB6N
The Rosa26-K18-hACE2 mouse model from Taconic Biosciences, developed in collaboration with Boston University, is an advanced human ACE2 knock-in model designed for SARS-CoV-2 and long COVID research. This translationally relevant model accurately reflects human COVID-19 infections, immune response, and post-acute sequelae (PASC), providing researchers with a powerful tool for the study of long-term inflammation and other systemic symptoms of long COVID.
| Model No. | Nomenclature | Genotype |
|---|---|---|
| 18675-M | C57BL/6NTac-Gt(ROSA)26Sortm7373_A-A10(KRT18-ACE2)Tac | ki/wt |
| 18675-F | C57BL/6NTac-Gt(ROSA)26Sortm7373_A-A10(KRT18-ACE2)Tac | ki/wt |
Nomenclature: C57BL/6NTac-Gt(ROSA)26Sortm7373_A-A10(KRT18-ACE2)Tac
Compared to other hACE2 models for the study of SARS-CoV-2 infection, the Taconic Rosa26-K18-hACE2 model demonstrates greater translatability to human COVID-19 infection and outcomes and demonstrates suitability for study of post-acute sequelae of SARS-CoV-2 infection (PASC), or long Covid.
This model has been submitted for publication as RAB/6N: "A Mouse Model of SARS-CoV-2-Driven Acute Maladaptive Responses and Chronic Systemic Disease"
Data from Kenney et. al. (2025) demonstrates several advantages of the Rosa26-K18-hACE2 model (RAB/6N) over K18-hACE2/6J.
| Rosa-26-K18-hACE2 (RAB/6N) | K18-hACE2/6J | |
| Improved ability to recover from acute diseases | Yes | No |
| Several days of steady lung function | Yes | No |
| Minimal incidence of severe brain infection | Yes | No |
| Suitable for study of PASC (long Covid) | Yes | No |
| Increased resistance to fatal outcomes | Yes | No |
| Fatal outcomes uncoupled from brain infection | Yes | No |
| Background strain with higher inflammatory potential | Yes | No |
Orders by weight: Taconic cannot accept orders by weight for this model. Please note that shipments may contain animals with a larger weight variation.
Recommended Controls
The recommended control for this model is C57BL/6NTac.
Origin
The Rosa26-K18-hACE2 mouse was developed by Taconic Biosciences in partnership with the National Emerging Infectious Disease Laboratories at Boston University. The model was created through targeted transgenesis to generate a constitutive Knock-In (KI) of the human angiotensin I converting enzyme 2 (ACE2) under the control of an epithelial promoter into a safe harbor locus of a C57BL6/NTac. The following elements were inserted into the Rosa26 locus (chromosome 6) using recombination-mediated cassette exchange (RMCE): the human KRT18 (keratin 18) 5’ region containing the promoter and intron 1, the human ACE2 open reading frame (ORF) with a translational enhancer, and the human KRT18 3’ region containing intron 6, exon 7 and the endogenous polyadenylation signal. This RMCE vector was transfected into a B6NTac embryonic stem cell (ESC) line equipped with RMCE docking sites at the ROSA26 locus.
Neomycin (NeoR) selection was used to isolate recombinant clones and the resulting constitutive KI allele was obtained with a single copy of human ACE2 expressed from the KRT18 promoter. The presence of the NeoR cassette terminated transcription for the ROSA26 promoter. The generated heterozygous animals were backcrossed to B6NTac and the line is maintained by crossing homozygous to wildtype B6NTac.
| hACE2 Strain | AC70 | AC22 | Rosa26-K18 | |
| Taconic Model # | 18222 | 18225 | 18675 | |
| Nomenclature | B6;C3-Tg(CAG-ACE2)70Ctkt | B6;C3(C)-Tg(CAG-ACE2)22Ctkt | C57BL/6NTac-Gt(ROSA)26Sortm7373_A-A10(KRT18-ACE2)Tac | |
| Transgene Location | X chromosome | Unplaced scaffold region, presumably on chromosome 10 | Rosa26 locus (safe harbor) on chromosome 6, under control of the K18 promoter | |
| Transgene Copy Number | 1 | ~30–40 | 1 | |
| SARS-CoV-2 Dose (US_WA-1/2020) | 103–106 TCID50 | 101 TCID50 | 105 TCID50 | 104 PFU (or ~103.8TCID50) |
| SARS-CoV-2 Dose (Delta B.1.617.2 variant) | N/A | N/A | 104 PFU (or ~103.8TCID50) | |
| SARS-CoV-2 Dose (Omicron BA.1 variant) | N/A | N/A | 104 PFU (or ~103.8TCID50) | |
| Mortality | 100% | 100% | 30–40% | WA-1 and Delta: 25% |
| Survival (days post-infection) | 4–5 | 6–10 | 7 | 15-65 depending on viral strain/titer |
| Clinical Signs | Severe weight loss, lethal infection | Moderate–severe weight loss, lethal infection | Moderate weight loss; lethal infection in some mice | Increased systemic inflammatory response |
| Site of Viral Replication | Primarily lung and brain | Primarily lung and brain | Primarily lung and brain | Primarily lung |
| Sex Differences | Minimal sex differences observed | Some sex differences observed; males display more severe disease phenotype | ||
| Other Information | LD50: 3 TCID50 ID50: 0.5 TCID50 | ID50: 101.5 TCID50 (~30 TCID50) | LD50: 1.84 x 104 PFU | |
Initial Publication:
Devin Kenney, Giulia Unali, Anna E. Tseng, Joseph Léger, Mao Matsuo, Aoife K. O’Connell, Christina McCooney, Samantha Good, Jack Norton, Fabiana Feitosa-Suntheimer, Mariano Carossino, Hans P. Gertje, Alexander Klose, Neal Paragas, Kevin P. Francis, Jennifer E. Snyder-Cappione, Anna Belkina, Jochen Welcker, Kenneth Albrecht, Ronald B. Corley, Christelle Harly, Nicholas A. Crossland, Florian Douam. (2025) A Mouse Model of SARS-CoV-2-Driven Acute Maladaptive Responses and Chronic Systemic Diseases. bioRxiv. 2025 Aug 13.670105; 670105.
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These characterization data are adapted from A Mouse Model of SARS-CoV-2-Driven Acute Maladaptive Responses and Chronic Systemic Diseases by Kenney et al, 2025. For full data and statistical analyses, please reference this source.
Figure 1: Comparison of hACE2 transgene expression between Rosa26-K18-hACE2 and K18-ACE2 mice. RT-qPCR analysis of hACE2 expression in lung, heart, kidney, brain and spleen of non-infected mice.
Figure 2: Rosa26-K18-hACE2 mice develop severe disease upon SARS-CoV-2 infection but are less susceptible to fatal outcomes than K18-hACE2 mice. 12- 22 week-old male and female Rosa26-K18-hACE2 and K18-hACE2 mice were infected intranasally with (A) SARS-CoV-2 WA-1 (B.1 variant) or (B) Delta (B.1.617.2 variant) at the indicated doses and monitored for 14 days. Survival percentages (left) and weight loss (right) are shown.
Figure 3: Fatal outcomes in Rosa26-K18-hACE2 mice are uncoupled from viral neuroinvasion. (A) Viral titers, determined by plaque-forming assay, in brain tissue at 2, 4, and 7-days post-infection. (B) Immunohistochemistry for SARS-CoV-2 Spike protein (brown stain) performed on coronal brain sections at 7 days post-infection. Reference brain sections are shown (top).
Figure 4: The lungs of Rosa26-K18-hACE2 mice display specific viral replication dynamics and histopathological features. (A) Viral titers, determined by plaque-forming assay, in lung tissue of Rosa26-K18-hACE2 and K18-hACE2 mice at 2, 4, and 7 days post-infection. (B) Quantification of the percent of CD3+ cells in lungs. (C) Percent lung consolidation.
Figure 5: Rosa26-K18-hACE2 mice display evidence of systemic and pulmonary post-acute sequelae. Rosa26-K18-hACE2 mice were infected with 1x105 PFU of SARS-CoV-2 Delta variant. Mice surviving infection (~20%) were characterized at 30 and 65 dpi. (A) Mean log2 fold-change of thirteen serum cytokine levels in surviving Rosa26-K18-hACE2 mice at 30 and 65 dpi compared to non-infected (mock) mice. (B) Quantification of CD11b+, CD19+, CD4+ and CD8+ cell numbers per mm2 of lung tissue at 30 and 65 dpi and in non-infected (mock) mice.
Figure 6: Gene network map of dysregulated disease pathways in tissues from the Rosa26-K18-hACE2 model of post-acute sequelae of SARS-CoV-2 (PASC) infection. Schematic showing select significantly upregulated (red) and downregulated (blue) genes in the lungs and brains of Rosa26-K18-hACE2 mice at 30 dpi and in the lungs and hearts at 65 dpi, which are linked to various disease pathways. Created with BioRender.com.
Conditions of Use for Taconic Transgenic Models™
Taconic Transgenic Models™ (Models) are produced and distributed under rights to patents and intellectual property licensed from various institutions. Taconic sells the Models to purchasers, grants to each purchaser a right under Taconic's rights in such licensed patents and intellectual property to use the purchased Model in consideration of purchasers' acknowledgement of and agreement to the Terms and Conditions for Taconic Models, Products and Services and the following terms of use:
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