| First Author | Yang B | Year | 2023 |
| Journal | Cell Discov | Volume | 9 |
| Issue | 1 | Pages | 43 |
| PubMed ID | 37080957 | Mgi Jnum | J:338826 |
| Mgi Id | MGI:7512713 | Doi | 10.1038/s41421-023-00536-0 |
| Citation | Yang B, et al. (2023) A tissue specific-infection mouse model of SARS-CoV-2. Cell Discov 9(1):43 |
| abstractText | Animal models play crucial roles in the rapid development of vaccines/drugs for the prevention and therapy of COVID-19, but current models have some deficits when studying the pathogenesis of SARS-CoV-2 on some special tissues or organs. Here, we generated a human ACE2 and SARS-CoV-2 N(F/F) knockin mouse line that constitutively expresses human ACE2 and specifically expresses SARS-CoV-2 N gene induced by Cre-recombinase. By crossing with Cre transgenic lines allowing for lung-specific and constitutive expression, we generated lung-specific (Sftpc-hACE2-N(F/F)) and constitutive SARS-CoV-2 N (EIIa-hACE2-N(F/F)) expressing mice. Upon intranasal infection with a SARS-CoV-2 GFP/DeltaN strain which can only replicate in SARS-CoV-2 N expressed cells, we demonstrated that both the Sftpc-hACE2-N(F/F) and EIIa-hACE2-N(F/F) mice support viral replication. Consistent with our design, viral replication was limited to the lung tissues in Sftpc-hACE2-N(F/F) mice, while the EIIa-hACE2-N(F/F) mice developed infections in multiple tissues. Furthermore, our model supports different SARS-CoV-2 variants infection, and it can be successfully used to evaluate the effects of therapeutic monoclonal antibodies (Ab1F11) and antiviral drugs (Molnupiravir). Finally, to test the effect of SARS-CoV-2 infection on male reproduction, we generated Sertoli cell-specific SARS-CoV-2 N expressed mice by crossing with AMH-Cre transgenic line. We found that SARS-CoV-2 GFP/DeltaN strain could infect Sertoli cells, led to spermatogenic defects due to the destruction of blood-testis barrier. Overall, combining with different tissue-specific Cre transgenic lines, the human ACE2 and SARS-CoV-2 N(F/F) line enables us to evaluate antivirals in vivo and study the pathogenesis of SARS-CoV-2 on some special tissues or organs. |
