A human-ACE2 knock-in mouse model for SARS-CoV-2 infection recapitulates respiratory disorders but avoids neurological disease associated with the transgenic K18-hACE2 model.

ABSTRACT: Animal models have been instrumental in elucidating the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and in testing coronavirus disease 2019 (COVID-19) vaccines and therapeutics. Wild-type (WT) mice are not susceptible to many SARS-CoV-2 variants, and therefore, transgenic K18-hACE2 mice have emerged as a standard model system. However, this model is characterized by a severe disease, particularly associated with neuroinfection, which leads to early humane endpoint euthanasia. Here, we established a novel knock-in (KI) mouse model by inserting the original K18-hACE2 transgene into the collagen type I alpha chain (COL1A1) locus using a recombinase-mediated cassette exchange (RMCE) system. Once the Col1a1-K18-hACE2 mouse colony was established, anima

SUBMITTER: Pons-Grifols A 

PROVIDER: S-EPMC12077128 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature