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Updated: Aug 2, 2025
Live Imaging and Quantification of Viral Infection in K18 hACE2 Transgenic Mice Using Reporter-Expressing Recombinant SARS-CoV-2
Published on: November 5, 2021
A tissue specific-infection mouse model of SARS-CoV-2
Bo Yang1,2, Chao Liu2,3, Xiaohui Ju4
1Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical Center, Shenzhen, Guangdong, China.
A novel mouse model expressing human ACE2 and SARS-CoV-2 N allows for studying COVID-19 pathogenesis in specific tissues. This model supports viral replication and aids in evaluating antiviral therapies and understanding SARS-CoV-2 effects on male reproduction.
Area of Science:
- Virology and Immunology
- Genetics and Animal Models
- Pathogenesis Research
Background:
- Current animal models for SARS-CoV-2 research have limitations in studying specific organ pathogenesis.
- A need exists for versatile models to investigate COVID-19 mechanisms and therapeutic efficacy.
- Understanding SARS-CoV-2 tropism is crucial for developing targeted interventions.
Purpose of the Study:
- To generate and characterize a novel inducible human ACE2 and SARS-CoV-2 N knockin mouse line.
- To utilize this model for studying SARS-CoV-2 pathogenesis in tissue-specific contexts.
- To evaluate the efficacy of antiviral drugs and monoclonal antibodies in vivo.
Main Methods:
- Generation of a human ACE2 and SARS-CoV-2 NF/F knockin mouse line.
- Creation of lung-specific (Sftpc-hACE2-NF/F) and constitutive (EIIa-hACE2-NF/F) expressing mice.
- Intranasal infection with a SARS-CoV-2 GFP/ΔN strain and assessment of viral replication and tissue tropism.
- Generation of Sertoli cell-specific N expressing mice to study male reproductive effects.
Main Results:
- Both Sftpc-hACE2-NF/F and EIIa-hACE2-NF/F mice supported SARS-CoV-2 replication.
- Lung-specific replication was observed in Sftpc-hACE2-NF/F mice; multi-tissue infection occurred in EIIa-hACE2-NF/F mice.
- The model successfully evaluated therapeutic monoclonal antibodies and antiviral drugs.
- SARS-CoV-2 infection in Sertoli cells led to spermatogenic defects and blood-testis barrier destruction.
Conclusions:
- The human ACE2 and SARS-CoV-2 NF/F knockin mouse line is a valuable tool for in vivo antiviral evaluation.
- This model enables detailed study of SARS-CoV-2 pathogenesis in specific organs, including male reproductive tissues.
- The findings highlight the potential for SARS-CoV-2 to impact male fertility.
