System Maintenance Notice

Please note that maintenance work is scheduled between 4 AM and 5 AM - CET. During this time, you may experience reduced performance. Thanks for your patience.

Publications

Journal Article Ppublish

PubMed: 39985688 DOI: 10.1007/s00335-025-10115-1

New mouse model for inducible hACE2 expression enables to dissect SARS-CoV-2 pathology beyond the respiratory system.

Mamm Genome 36(2):403-416

Authors: Federica Gambini, Dominik Arbon, Petr Nickl, Vaclav Zatecka, Olha Fedosieieva, Juraj Labaj, Vendula Novosadova, Jana Trylcova, Jan Weber, Jan Prochazka, Jana Balounova, Radislav Sedlacek

Affiliations

  • Laboratory of Transgenic Models of Diseases, Institute of Molecular Genetics of the Czech Academy of Sciences, Videnska 1083, Prague, 142 20, Czech Republic.
  • Czech Centre for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences, Prumyslova 595, Vestec, 252 50, Czech Republic.
  • Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Prague, 166 10, Czech Republic.
  • Czech Centre for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences, Prumyslova 595, Vestec, 252 50, Czech Republic.
  • Laboratory of Transgenic Models of Diseases, Institute of Molecular Genetics of the Czech Academy of Sciences, Videnska 1083, Prague, 142 20, Czech Republic.
  • Czech Centre for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences, Prumyslova 595, Vestec, 252 50, Czech Republic.

Abstract

The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection is not limited to the respiratory tract as receptors, including the angiotensin-converting enzyme 2 (ACE2), are expressed across many tissues. This study employed a new conditional mouse model, Rosa26 creERT2/chACE2, which expresses human ACE2 (hACE2) across multiple organs, to investigate the effects of SARS-CoV-2 infection beyond the respiratory system. This strain demonstrated susceptibility to SARS-CoV-2 infection in a dose and sex-dependent manner, showing that infected male mice exhibited more severe disease outcomes, including significant weight loss, pronounced lung pathology and dysfunction, and increased mortality, compared to females. In contrast to intratracheal infection, intranasal virus administration facilitated viral spread to the brain, thereby underscoring the nasal route's role in the pathogenesis of neurological manifestations. Intranasal infection also led to increased innate immune system activation as compared to intratracheal virus administration, even though both routes activated the adaptive immune response. This model provides a valuable tool to study SARS-CoV-2 in individual tissues or use a multisystemic approach, and it also advances possibilities for preclinical evaluation of antiviral therapies and vaccine strategies.

MeSH

Sars-Cov-2, Respiratory System, Pathology, Viruses, Genomic Library, Severe Acute Respiratory Syndrome-Related Coronavirus, Tissues, Genome, Human, Infections