- Mice expressing human ACE2 are susceptible to infection by SARS-CoV-2, the virus that causes COVID-19. The hACE2 AC22 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.
- hACE2 AC22 are lethality-resistant and may be useful for studies of sublethal SARS-CoV-2 infection. A SARS-CoV-2 dose (105 TCID50) that is fully lethal in hACE2 AC70 mice results in only partial lethality in hACE2 AC22 mice, and viral titration will likely provide sharper resolution to sublethal effects of SARS-CoV-2 in the AC22 line. For experiments where a lethal SARS-CoV-2 infection model is preferred, we recommend hACE2 AC70.
- Following intranasal infection with 105 TCID50 SARS-CoV-2, 40% of AC22 mice died by 7 dpi. Personal communication, Kent Tseng, UTMB.
- hACE2 AC22 mice express human ACE2 in lungs, kidney, brain, stomach, small intestine, cecum, colon, muscle and heart.
- Due to the susceptibility of this mouse to SARS-CoV-2 and the current prevalence of this virus in the human population, special biosecurity precautions are required for housing and husbandry for hACE2 mice — both naïve mice and mice used in infection studies. A signed Acknowledgement of Biosecurity Precautions for Models Susceptible to SARS-CoV-2 is required prior to order.
- The hACE2 AC22 line is also susceptible to SARS-CoV, the virus which causes SARS. Following intra-nasal infection with SARS-CoV, hACE2 AC22 mice lose weight (~30%) but recover without observed mortality. SARS-CoV virus replicates primarily in lung and, to a lesser extent, brain, and hACE2 AC22 mice develop moderate interstitial pneumonia.
- The AC22 transgene is integrated into an unplaced scaffold region, presumably on chromosome 10. It is estimated at 30-40 copies.
- 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.
| Susceptibility to SARS-CoV-2 |
|---|
| hACE2 Strain | Taconic model # | Nomenclature | Transgene Location | Transgene Copy Number | SARS-CoV-2 Dose (US_WA-1/2020) | Mortality | Survival (days post-infection) | Clinical Signs | Site of Viral Replication | Sex Differences | Other Information |
| AC70 | 18222 | B6;C3-Tg(CAG-ACE2)70Ctkt | X chromosome | 1 | 103-106 TCID50 | 100% | 4-5 | Severe weight loss, lethal infection | Primarily lung and brain | Minimal sex differences observed | |
| 101 TCID50 | 100% | 6-10 | Moderate-severe weight loss, lethal infection | Primarily lung and brain | | LD50: 3 TCID50
ID50: 0.5 TCID50 |
| AC22 | 18225 | B6;C3(C)-Tg(CAG-ACE2)22Ctkt | an unplaced scaffold region, presumably on chromosome 10 | ~30-40 | 105 TCID50 | 30-40% | 7 | Moderate weight loss and lethal infection in some mice | Primarily lung and brain | | ID50: 101.5 TCID50
(~30 TCID50) |
Orders by weight: Taconic cannot accept orders by weight for this model. Please note that shipments may contain animals with a larger weight variation.
Genetic Background:
C57BL/6 is the predominant background strain, with contributions from C3H and BALB/c, as determined by data from our 2050-SNP panel background characterization. The strain background is being moved onto C57BL/6NTac via backcrossing. Origin:
The hACE2 AC22 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 AC22 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. Color:
Black and Black Agouti Species:
Mouse 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.
