hACE2 AC70 Mouse

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hACE2 AC70 Mouse Model
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Mixed C57BL/6 x C3H Background

  • Model #
  • Genotype
  • Nomenclature
  • 18222-F
    tg/wt
    B6;C3-Tg(CAG-ACE2)70Ctkt
  • 18222-F
    wt/wt
    B6;C3-Tg(CAG-ACE2)70Ctkt
  • 18222-M
    tg/y
    B6;C3-Tg(CAG-ACE2)70Ctkt
  • 18222-M
    wt/y
    B6;C3-Tg(CAG-ACE2)70Ctkt

SARS-CoV-2 provokes lethal infection in hACE2 AC70 mice

SARS-CoV-2 provokes lethal infection in hACE2 AC70 mice

  • 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 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 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. A signed Acknowledgement of Biosecurity Precautions for Models Susceptible to SARS-CoV-2 is required prior to order.
  • 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.

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 and 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: Females readily available. 8+ week lead time for males at typical study ages.

Genetic Background:

C57BL/6 is the predominant background strain, with contributions from C3H. The strain background is being moved onto C57BL/6NTac via backcrossing.

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.

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.


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.

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 10 to the power of 6 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 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.
hACE2 AC70 mice express higher levels of human ACE2 mRNA in the lung compared to mouse Ace2 mRNA.
Figure 2: hACE2 AC70 mice express higher levels of human ACE2 mRNA in the lung compared to mouse Ace2 mRNA.
Image showing 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.
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.
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.
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