hACE2 AC22 Mouse

Random Transgenic

hACE2 AC22 Mouse model

Mixed C57BL/6 x C3H Background

  • Model #
  • Genotype
  • Nomenclature
  • 18225-F
    tg/wt
    B6;C3(C)-Tg(CAG-ACE2)22Ctkt
  • 18225-F
    wt/wt
    B6;C3(C)-Tg(CAG-ACE2)22Ctkt
  • 18225-M
    tg/wt
    B6;C3(C)-Tg(CAG-ACE2)22Ctkt
  • 18225-M
    wt/wt
    B6;C3(C)-Tg(CAG-ACE2)22Ctkt
  • 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, all hACE2 AC22 mice lost significant bodyweight by 6 days post-infection (dpi). 40% of AC22 mice died by 7 dpi, whereas wild type control littermates maintained bodyweight and no mice died. 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 StrainTaconic model #NomenclatureTransgene LocationTransgene Copy NumberSARS-CoV-2 Dose (US_WA-1/2020)MortalitySurvival (days post-infection)Clinical SignsSite of Viral ReplicationSex DifferencesOther Information
AC7018222B6;C3-Tg(CAG-ACE2)70CtktX chromosome1103-106 TCID50100%4-5Severe weight loss, lethal infectionPrimarily lung and brainMinimal sex differences observed 
101 TCID50100%6-10Moderate-severe weight loss, lethal infectionPrimarily lung and brain LD50: 3 TCID50
ID50: 0.5 TCID50
AC2218225B6;C3(C)-Tg(CAG-ACE2)22Ctktan unplaced scaffold region, presumably on chromosome 10~30-40105 TCID5030-40%7Moderate weight loss, lethal infection in some micePrimarily 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.

Availability: Shipments will start in April 2021.

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 200781 (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 200983 (11), 5451–5465.


A signed Acknowledgement of Biosecurity Precautions for Models Susceptible to SARS-CoV-2 is required prior to order.
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:
  • Title to these Models and biological materials derived from them remains with Taconic.
  • The Models will be used for research purposes only.
  • The Models will not be bred or cross-bred except to obtain embryos or fetuses required for research purposes unless additional rights have been granted in writing by Taconic.
  • The Models and biological materials derived from them will not be distributed to third parties or used for commercial purposes.
  • Non-profit purchasers may not use this Model and/or biological materials derived from it in sponsored research or contract research studies unless it is purchased at the for-profit price.
NOTE: Non-profit users may obtain breeding rights via execution of a limited breeding agreement. This agreement carries a modest yearly fee and permits breeding, backcrossing and crossbreeding. Contact Taconic to request an agreement.

A

Chart shows percentage change in bodyweight compared to days post-infection for the challenged mice, that were monitored daily for weight loss (% ± SEM).

B

Chart shows percentage of survival compared to days post-infection for the challenged mice, that were monitored daily for weight loss (% ± SEM).

C

Chart shows clinical score compared to post-infection for the challenged mice, that were monitored daily for weight loss (% ± SEM).
Figure 1: hACE2 AC22 mice are permissive to SARS-CoV-2 infection with 40% mortality when challenged with 105 TCID50. Female human ACE2 transgene-positive (Transgenic AC22) and -negative (Wild Type) littermates from the AC22 line were infected intranasally with 105 TCID50 of SARS-CoV-2 (US_WA-1/2020). Challenged mice were monitored daily for weight loss (% ± SEM) (A), accumulated mortality (B) and clinical score (C). Personal communication, Kent Tseng, UTMB.
Chart shows hACE2 AC22 mice generally express higher levels of human ACE2 mRNA in the lung compared to mouse Ace2 mRNA
Figure 2: hACE2 AC22 mice generally express higher levels of human ACE2 mRNA in the lung compared to mouse Ace2 mRNA.
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