hACE2-All CDS-B6J Mice

Catalog Number: C001191

Strain Name: C57BL/6JCya-Ace2em1(hACE2)/Cya

Genetic Background: C57BL/6JCya

Reproduction: Heterozygous male x Homozygous female

 

Strain Description

Angiotensin-converting enzyme 2 (ACE2) is the predominant cell surface receptor for SARS-CoV-2 virus infection in humans, but due to interspecies differences, the SARS-CoV-2 virus is unable to bind to ACE2 receptors in most wild-type rodents, including mice. Replacement of mouse Ace2 with human ACE2 by gene editing techniques resulted in humanized ACE2 mice (hACE2) that stably express human ACE2 receptors for COVID-19 studies.

This strain is a mouse Ace2 gene humanization model that uses gene editing technology to replace the endogenous mouse Ace2 gene sequence with human ACE2 CDS, preserving the mouse signal peptide sequence and achieving hACE2 expression directed by the endogenous mouse Ace2 regulatory element. This gene is located on the mouse chromosome X and homozygous females and heterozygous males are viable and fertile.

Strain Strategy

Application

  • COVID-19 and related diseases research.
  • COVID-19 vaccine and antibody drug evaluation.

 

Validation Data

1. Detection of the expression of human ACE2 mRNA


Figure 1. The detection of the expression of human ACE2 protein in hACE2-All CDS-B6J and wild-type mice. Different tissues of hACE2-All CDS-B6J (NKI1677-163) and wild-type (WT1) mice were taken for qPCR validation, and the results showed that hACE mRNA expression was present in the small intestine, large intestine, kidney, lung, and trachea of hACE2-All CDS-B6J mice.

2. Detection of the expression of human ACE2 protein


Figure 2. Detection of the expression of human ACE2 protein in hACE2-All CDS-B6J mice. Different tissues from this model were taken and processed for immunohistochemical assays to detect the expression of human ACE2 (hACE2). The results showed that hACE2 protein was expressed in the intestine, lung, trachea, and kidney of this model.

Publication

a. Antibody Discovery


Figure 3. Efficacy of shark-derived antibody vnarbody 20G6 in preventing SARS-CoV-2 infection and  treatment after infection in hACE2-All CDS-B6J mice[1].


Figure 4. SARS-CoV-2 antibody R1-32 treatment attenuates lung inflammation in hACE2-All CDS-B6J mice after SARS-CoV-2 infection[2]

 

b. Complication studies


Figure 5. SARS-CoV-2 Spike protein induces intestinal permeability of hACE2-All CDS-B6J through VEGF overproduction[3].

 

c. Preventive drug screening


Figure 6. VitC administration reduces ACE2 protein levels and limits SARS-CoV-2 infection in hACE2-All CDS-B6J mice[4].



References:

[1]Feng Bo,Chen Zhilong,Sun Jing et al. A Class of Shark-Derived Single-Domain Antibodies can Broadly Neutralize SARS-Related Coronaviruses and the Structural Basis of Neutralization and Omicron Escape.[J] .Small Methods, 2022: e2200387.
[2]He P, Liu B, Gao X, et al. SARS-CoV-2 Delta and Omicron variants evade population antibody response by mutations in a single spike epitope[J]. Nature Microbiology. 2022 Oct;7(10):1635-1649.
[3]Zeng F M, Li Y, Deng Z, et al. SARS-CoV-2 spike spurs intestinal inflammation via VEGF production in enterocytes[J]. EMBO molecular medicine, 2022, 14(5): e14844
[4]Zuo, Yibo, et al. "Vitamin C is an efficient natural product for prevention of SARS-CoV-2 infection by targeting ACE2 in both cell and in vivo mouse models." bioRxiv (2022).
[5]Liang S, Bao C, Yang Z, Liu S, Sun Y, Cao W, Wang T, Schwantes-An TH, Choy JS, Naidu S, Luo A, Yin W, Black SM, Wang J, Ran P, Desai AA, Tang H. SARS-CoV-2 spike protein induces IL-18-mediated cardiopulmonary inflammation via reduced mitophagy. Signal Transduct Target Ther. 2023 Mar 9;8(1):108.