K18-hACE2-2A-CreERT2 Mice

Catalog Number: C001244

Strain Name: C57BL/6JCya-Igs2em1(K18-hACE2-2A-CreERT2)/Cya

Genetic Background: C57BL/6JCya

Reproduction: Homozygote x Homozygote

 

Strain Description

 Angiotensin-converting enzyme 2 (ACE2) is the predominant cell surface receptor for SARS-CoV-2 virus infection in humans, but due to species differences, the SARS-CoV-2 virus is unable to bind to the ACE2 receptor in most wild-type rodents. By inserting the "K18 promoter-human ACE2 CDS-P2A-CreERT2-rBGpA" sequence into the safety harbor of the mouse genome through gene editing technology, humanized ACE2 mice (K18-hACE2) that stably express the human ACE2 receptor can be obtained. This mouse model expresses human ACE2 protein in epithelial cells under the regulation of the human keratin K18 promoter, including the most initially infected airway epithelial cells. This model also carries the CreERT2 element, which can be induced by tamoxifen to express the Cre recombinase, so this strain can be used either alone for COVID-19 and related studies or in combination with flox mice for studying the role of specific host genes in response to SARS-CoV-2 virus infection.

K18-hACE2 mice can be infected with the SARS-CoV-2 virus, resulting in severe disease characterized by weight loss, rapid respiration, hunched posture, and immobility. This strain responds to viral attack in a dose-dependent manner, thus allowing the study of severe acute respiratory disease in mice heavily infected by high doses of the virus, as well as the long-term effects of low doses of mild infection.

The model should be handled in strict accordance with the guidelines for the prevention of SARS-CoV-2 virus infection in humans as specified by CDC&ABSA&WHO, and appropriate personal protective equipment (PPE) and handling methods should always be used when using these mice for research.

Allele Type

The "K18 promoter-Kozak-human ACE2 CDS-P2A-CreERT2-rBGpA" gene expression element was inserted into the H11 safety harbor in C57BL/6JCya mice.


Application

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

 

Validation Data

1. Detection of the expression of human ACE2 protein


Figure 1. The detection of the expression of human ACE2 protein in K18-hACE2 mice. After the model was established, different tissues of the humanized model were verified by western blot (WB), and the results showed that the expression was found in the kidney, brain, lung, trachea, colon, and small intestine, indicating that the humanized model could successfully express human ACE2 protein.

 

2. SARS-CoV-2 virus infection


Figure 2. Viral infection test by dropping SARS-CoV-2 virus into K18-hACE2 mice through the nasal cavity. Experimental data show that K18-hACE2 mice can be successfully infected by the wild strain of SARS-CoV-2 and produce high virus titers in vivo, and the experiment was conducted in a high-level biosafety laboratory.

 

Publication
[1] Yu S, Zheng X, Zhou B, Li J, Chen M, Deng R, Wong G, Lavillette D, Meng G. SARS-CoV-2 spike engagement of ACE2 primes S2' site cleavage and fusion initiation. Proc Natl Acad Sci U S A. 2022 Jan 4;119(1):e2111199119.