Application Areas:
Live production of model 18222 has ceased. This model is now available via Taconic’s Cryopreserved Repository. Customers who need continued access may inquire about licensing options for in-house breeding or cryorecovery.
hACE2 AC70 Mouse
View:
Select One
- Description
- Data
- Price & Licensing
- Overview
- Genetics
- Guides & Publications
- Applications & Therapeutic Areas
Overview
Nomenclature: B6;C3-Tg(CAG-ACE2)70Ctkt
- Mice expressing human ACE2 are susceptible to infection by SARS-CoV-2, the virus that causes COVID-19. The hACE2 AC70 mouse model expresses human ACE2 cDNA under the control of the CAG promoter.
- ACE2 is the receptor bound by SARS-CoV-2 and SARS-CoV spike proteins during viral entry into host cells; these spike proteins have much higher binding affinity to human ACE2 compared to mouse ACE2.
- Following intranasal infection with 106 TCID50 SARS-CoV-2, hACE2 AC70 mice lost significant bodyweight by 3 days post-infection (dpi) and 100% of mice died by 5 dpi, whereas wild type control littermates maintained bodyweight and no mice died. Personal communication, Kent Tseng, UTMB. Please see hACE2 AC22 if interested in a lethality-resistant SARS-CoV-2 infection model.
- According to published reports, hACE2 AC70 mice express human ACE2 in lungs, kidneys, liver, heart, skeletal muscle, spleen, lymph nodes, pancreas, gastrointestinal smooth muscle and ganglia, vascular endothelium, adrenal and central nervous system tissues. Taconic has confirmed hACE2 mRNA expression in hemizygous male and female mice in the following tissues: lung, brain, stomach, small intestine, cecum, colon, kidney, heart and muscle. For most tissues, mRNA expression of human ACE2 is significantly higher than that of mouse Ace2.
- Due to the susceptibility of this mouse to SARS-CoV-2, these mice should be handled in a manner consistent with appropriate guidelines for prevention of human infection with the SARS-CoV-2 virus. Proper PPE and handling methods should be used at all times. Learn more here.
- TThe hACE2 AC70 line is also susceptible to SARS-CoV, the virus which causes SARS. Following intra-nasal infection with SARS-CoV, hACE2 AC70 mice rapidly lose weight and die within days. SARS-CoV virus replicates primarily in lung and brain, and hACE2 AC70 mice develop moderate interstitial pneumonia.
- The AC70 transgene is located on the X chromosome, with one intact copy of the transgene.
- Learn more about hACE2 mice for COVID-19 research.
- Non-profit researchers may obtain breeding rights by executing a limited breeding license. This license carries a nominal fee.
| 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 | |
Orders by weight: Taconic cannot accept orders by weight for this model. Please note that shipments may contain animals with a larger weight variation.
Availability: Females readily available. 8+ week lead time for males at typical study ages.
Recommended Controls
The recommended control for this model is wild type (WT) littermates.
Origin
The hACE2 AC70 Mouse was generated by Kent Tseng et al. at the University of Texas Medical Branch at Galveston via pronuclear microinjection of a transgene into C57BL/6J x C3H/HeJ F1 zygotes. The transgene consists of human ACE2 cDNA under the control of the CAG promoter, consisting of the cytomegalovirus immediate-early enhancer and the chicken beta-actin promoter with the rabbit globin splicing and polyadenylation site. Multiple founder lines were established, including the AC70 line, which was subsequently backcrossed to C57BL/6. Taconic received the line in 2020, and the line was expanded via IVF rapid expansion using C57BL/6NTac females and hemizygous males. Taconic maintains breeding using C57BL/6NTac females by hemizygous males and/or hemizygous females by C57BL/6NTac males.
SARS-CoV-2 provokes lethal infection in hACE2 AC70 mice
Genetics
Guides & Publications
Initial Publication:
- Tseng, C.-T. K.; Huang, C.; Newman, P.; Wang, N.; Narayanan, K.; Watts, D. M.; Makino, S.; Packard, M. M.; Zaki, S. R.; Chan, T.-S.; Peters, C. J. Severe Acute Respiratory Syndrome Coronavirus Infection of Mice Transgenic for the Human Angiotensin-Converting Enzyme 2 Virus Receptor. Journal of Virology 2007, 81 (3), 1162–1173.
- Yoshikawa, N.; Yoshikawa, T.; Hill, T.; Huang, C.; Watts, D. M.; Makino, S.; Milligan, G.; Chan, T.; Peters, C. J.; Tseng, C.-T. K. Differential Virological and Immunological Outcome of Severe Acute Respiratory Syndrome Coronavirus Infection in Susceptible and Resistant Transgenic Mice Expressing Human Angiotensin-Converting Enzyme 2. Journal of Virology 2009, 83 (11), 5451–5465.
Applications & Therapeutic Areas
- Infectious Disease
- Vaccine Research
Data
Download document: Virulence of SARS-CoV-2 variants Washington (US_WA-1/2020), Delta (B.1.617.2), and Omicron sub-variants (BA.4/.5) in the hACE2 AC70 mouse. Data provided by Bioqual, Inc.
Figure 1: SARS-CoV-2 infection of human ACE2 transgenic AC70 mice resulted in an acute onset of disease and mortality. Human ACE2 transgene-positive (Transgenic AC70) and -negative (Wild type) littermates from the AC70 line were infected intranasally with 106 TCID50 of SARS-CoV-2 (US_WA-1/2020). Challenged mice were monitored daily for weight loss (% ± SEM) (A) and accumulated mortality (B). Personal communication, Kent Tseng, UTMB.
Figure 2: hACE2 AC70 mice express higher levels of human ACE2 mRNA in the lung compared to mouse Ace2 mRNA.
Figure 3: Immunohistochemical analysis of paraffin-embedded brain (left), spleen (middle), and lung (right) from wild type (wt/wt, top)and hACE2 AC70 (tg/wt, bottom) mice using ACE2 (E5O6J) XP® Rabbit mAb #92485 from Cell Signaling Technology, Inc.
- Pricing
- Licensing
- Select my Health Standard
- Get Custom Pricing Guide
Pricing
Cryopreserved models are invoiced upon shipment of recovered animals. Once orders are placed, the full purchase price will be applied if the order is canceled. For orders greater than 4 animals, please contact Taconic for options.
Fees for Taconic Transit Cages™ and freight are in addition to the price above.
Licensing
Customers may purchase this model by signing the appropriate Terms of Sale (below) and providing a PO.
This model is sold under terms which grant perpetual use rights.
This model is sold under terms which grant perpetual use rights.
Select my Health Standard
Need help choosing the right Taconic Biosciences health standard for your research?
Use the Health Standard Selector to enter your exclusion list. The tool will tell you which health standards meet your requirements.
Get custom pricing guide
Schedule A Scientific Consultation
Connect directly with a member of our Scientific Solutions team who can help you select the most appropriate model and maximize your experimental success.
