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bioRxiv · 10.1101/2024.11.10.622838

Generation of a biosafety mouse model infection for SARS-CoV-2 replicon delivery particles

Li, Y.·Huang, X.·Deng, J.·Tan, X.·Liu, Q.·Zhou, L.·Chen, Y.
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Abstract

Animal models are essential for understanding the pathogenesis of SARS-CoV-2 and for developing therapeutic strategies. Replicon delivery particles (RDPs) were a component of trans-complementary systems for SARS-CoV-2, which is a safe and convenient tool in researching SARS-CoV-2 in animal biosafety level-II laboratory (ABSL-2). Here, we constructed a mouse model that conditional expressing SARS-CoV-2 N on the background of the K18-hACE2 KI mice. The SARS-CoV-2 N with flanked loxP-stop-loxP sequence was under the CAG promoter, and this cassette was knocked into the Tiger locus of mouse by CRISPR-Cas9 (K18-hACE2-N KI). By mating K18-hACE2-N KI mice with Cre tool mice, the offspring can express SARS-CoV-2 N (Cre-N-hACE2 KI) systemically and in a tissue-specific manner. Cre-N-hACE2 KI exhibited susceptibility to the SARS-CoV-2 {Delta}N-GFP/HBiT infection. The viral loads in lung exhibited a mountain-like trend, peaking at 4 days post-infection, and lung injuries can be observed. Overall, we demonstrated a mouse model infection for SARS-CoV-2 {Delta}N-GFP/HBiT to understand SARS-CoV-2 pathogenesis.

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Li, Y., Huang, X., Deng, J., Tan, X., Liu, Q., Zhou, L., Chen, Y.. 2024-11-10. Generation of a biosafety mouse model infection for SARS-CoV-2 replicon delivery particles. https://doi.org/10.1101/2024.11.10.622838

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