key: cord-1055978-rm721i3a
authors: Liu, Feng-Liang; Wu, Kaixin; Sun, Jiaoyang; Duan, Zilei; Quan, Xiongzhi; Kuang, Junqi; Chu, Shilong; Pang, Wei; Gao, Han; Xu, Ling; Li, Ying-Chang; Zhang, Hai-Lin; Wang, Xue-Hui; Luo, Rong-Hua; Feng, Xiao-Li; Schöler, Hans R; Chen, Xinwen; Pei, Duanqing; Wu, Guangming; Zheng, Yong-Tang; Chen, Jiekai
title: Rapid generation of ACE2 humanized inbred mouse model for COVID-19 with tetraploid complementation
date: 2020-11-24
journal: Natl Sci Rev
DOI: 10.1093/nsr/nwaa285
sha: 673f11726a7db655188b492d1862d7a1b515b93e
doc_id: 1055978
cord_uid: rm721i3a

nan

Although monkeys and pigs can be infected with SARS-CoV-2, they generally have a long growth cycle and a large size that is difficult to handle in large quantities. However, the readily available rats and mice are not susceptible to SARS-CoV-2 due to the difference in ACE2 (angiotensin-converting enzyme 2), the receptor mediating cell-entry of SARS-CoV-2(1). Thus, the key to establishing a mouse model of COVID-19 is to make the mice to express human ACE2 protein and therefore become SARS-CoV-2 susceptible.

However, the recent reported COVID-19 mouse models using random insertion transgene approach (2, 3) or adenoviral approach to express hACE2 (4) , lack the tissue-specificity of hACE2 expression and might not replicate (E) Testis, small intestine and lung of hACE2 mice were stained for hACE2 (red), ACTIN filaments (green) and DAPI (blue). Scale bars, 50μm.

(F) Lung, airway, small intestine and Fecal samples were collected after mice sacrifice at the indicated days post-infection. Total RNA was extracted and subjected to qRT-PCR for viral loading assay. The left y-axis showed the viral loading of each tissue or per gram feces, while the right y-axis showed the percentage of tissues containing SARS-CoV-2.

SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice

Pathogenesis of SARS-CoV-2 in Transgenic Mice Expressing Human Angiotensin-Converting Enzyme 2

Generation of a Broadly Useful Model for COVID-19 Pathogenesis, Vaccination, and Treatment

Comparison of tetraploid blastocyst microinjection of outbred Crl:CD1(ICR), hybrid B6D2F1/Tac, and inbred C57BL/6NTac embryos for generation of mice derived from embryonic stem cells

Fecal specimen diagnosis 2019 novel coronavirusinfected pneumonia

Infectious SARS-CoV-2 in Feces of Patient with Severe COVID-19

Multiorgan and Renal Tropism of SARS-CoV-2

Pathological findings of COVID-19 associated with acute respiratory distress syndrome

A human neutralizing antibody targets the receptor binding site of SARS-CoV-2

The authors declare no competing interests.