New Breakthrough of Cell and its Sub-Journals: Chinese Scientists Successfully Developed SARS-CoV-2 Mouse Model

June 3, 2020 /PRNewswire
BIOON /- Animal models are critical to the pathology of the virus, vaccine development, and drug screeningNon-human primate models are commonly used in preclinical experiments, but they are expensive, inconvenient to use, and require relatively complex facilities, which limit the application of this animal model in SARS-CoV-2The mouse model is a more ideal preclinical experimental model because it is cheap, more readily available, and has simple feeding conditionsBut mice did not express SARS-CoV-2 for human angiotensin conversion enzyme 2 (ACE2) that enters human cellsTherefore, the development of new mouse models for SARS-CoV-2 research will help drive related virological research and research and development of therapeutic targets and drugsrecently, in two research papers published in Cell and Cell Host and Microbe, scientists from China developed mouse models that can be used for SARS-CoV-2 and COVID-19 studies, providing a convenient, practical and affordable animal model for SARS-CoV-2 and COVID-19image source: Cellin cell (Pathogenesis of SARS-CoV-2 in transgenic mice expressing human angiotensin-converting enzyme 2.), from the Wuhan Institute of Viruses of the Chinese Academy of Sciences, the University of The Chinese Academy of Sciences, the Tongji School of Medicine of Huazhong University of Science and Technology, and the University of North Carolina at Chapel HillResearchers developed a genetically modified mouse (HFH4-hACE2 in C3B6 mice) that expressed human angiotensin conversion enzyme 2 (ACE2), and the researchers found that the intestinal, pneumonia symptoms and pathological characteristics of the mice after SARS-CoV-2 infection were similar to those in patients with COVID-19the virus was detected, the researchers determined that the lungs of the mice were the main organ of the virus, but the researchers also detected viral RNA in the eyes, heart and brain of some miceIn addition, the researchers isolated the entire genome of SARS-CoV-2 from the lungs and brain tissue of infected micefinally, researchers found that preexposure to SARS-CoV-2 prevented severe pneumonia in mice from reinfectionOverall, this study shows that this new hACE2 mouse model is a very valuable tool for studying SARS-CoV-2 vaccines and drugssecond study, published in Cell Host of SARS-CoV-2 and infectiones pathogenis, the researchers recreated the characteristics observed in human patients in a mouse model infected with SARS-CoV-2 Using CRISPR/Cas9 gene editing, the researchers were able to produce mice that were able to produce human angiotensin-conversion enzyme II (hACE2), a receptor that is combined with SARS-CoV-2 and used to enter human cells "A small animal model is very much needed to replicate the clinical processes and pathologies observed in PATIENTs with COVID-19," said Wang You-Chun, a co-senior study author at the National Institute of Food and Drug Control (NIFDC) in The animal models described here provide a useful tool for studying SARS-CoV-2 infection and spread Wang and his colleagues used CR
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R/Cas9 to produce a mouse model that expressed hACE2 According to the authors, their mouse models have some advantages in simulating SARS-CoV-2 infection sinted with other genetically engineered mice that express hACE2 hACE2 is not randomly inserted, but is precisely inserted into a specific location on the X chromosome, which completely replaces the mouse version of the protein In addition, this is a genetically stable model with little difference between individuals The viral RNA load in the lungs is much higher, and the resulting distribution of hACE2 in various tissues is more consistent with that of humans after contracting SARS-CoV-2 through the nose, genetically engineered mice showed evidence of strong replication of viral RNA in the lungs, trachea and brain "The presence of viral RNA in the brain is somewhat unexpected because only a few patients with COVID-19 have neurological symptoms," said Cheng-Feng Qin, a senior study author at the Chinese Academy of Military Medical Sciences (AMMS) "
SARS-CoV-2 S protein binds to hACE2 into host cells and is also present in lung tissue and brain cells In addition, the researchers identified the main airway cells targeted by SARS-CoV-2 as Clara cells that produce the CC10 protein "Our results provide the first evidence that SARS-CoV-2 is the primary target cell in the lungs," said Yu-Sen Zhou, co-senior study author of AMMS image source: Cell Host and Microbe
In addition, the mice also developed interstitial pneumonia, which affects the tissues and space around the lung air bag, causing inflammatory cells to leach, thickening the structure of the isolated airbags, and damage to blood vessels Older mice showed more severe lung damage and signaling molecules called cytokines than younger mice In summary, these characteristics summarize the characteristics observed in PATIENTs with COVID-19 When researchers injected SARS-CoV-2 into their stomachs, two of the mice showed high levels of viral RNA in their trachea and lungs The S protein is also present in lung tissue and shows signs of inflammation The authors believe that these findings are consistent with observed gastrointestinal symptoms such as diarrhea, abdominal pain, and vomiting in patients with COVID-19 However, a 10-fold dose of SARS-CoV-2 is required through the stomach rather than through the nose Future studies using these mouse models may help shed light on how SARS-CoV-2 invades the brain and how the virus survives in the gastrointestinal environment and invades the respiratory tract "The hACE2 mice described in our study provide a small animal model for understanding the unexpected clinical manifestations of HUMAN SARS-CoV-2 infection, which is also valuable for testing vaccines and treatments to combat SARS-CoV-2," the researchers said (biovalleybioon.com) References: ssesis of SARS-CoV-2 in transgenic mice expressing human angiotensin-converting enzyme 2 Published: May 21, 2020DOI: https://doi.org/10.10.1016/j.cell.2020.05.027
Mouse model mimics SARS-CoV-2 infection in humans
Shi-Hui-Hui-al, -A-mouse model of SARS-CoV-2, , DOI: 10.1016/j.chom.2020.05.020