tetano
Editor, Senior Moderator
Mamm Genome
. 2024 Mar 15.
doi: 10.1007/s00335-024-10033-8. Online ahead of print. Generation of a humanized mAce2 and a conditional hACE2 mouse models permissive to SARS-COV-2 infection
I-Wen Song[SUP] 1 [/SUP], Megan Washington[SUP] 1 [/SUP], Carolina Leynes[SUP] 1 [/SUP], Jason Hsu[SUP] 2 [/SUP], Kempaiah Rayavara[SUP] 3 [/SUP], Yangjin Bae[SUP] 1 [/SUP], Nele Haelterman[SUP] 1 [/SUP], Yuqing Chen[SUP] 1 [/SUP], Ming-Ming Jiang[SUP] 1 [/SUP], Aleksandra Drelich[SUP] 3 [/SUP], Vivian Tat[SUP] 4 [/SUP], Denise G Lanza[SUP] 1 [/SUP], Isabel Lorenzo[SUP] 1 [/SUP], Jason D Heaney[SUP] 1 [/SUP], Chien-Te Kent Tseng[SUP] 3 [/SUP], Brendan Lee[SUP] 1 [/SUP], Ronit Marom[SUP] 5 [/SUP]
Affiliations
The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) remains a public health concern and a subject of active research effort. Development of pre-clinical animal models is critical to study viral-host interaction, tissue tropism, disease mechanisms, therapeutic approaches, and long-term sequelae of infection. Here, we report two mouse models for studying SARS-CoV-2: A knock-in mAce2[SUP]F83Y,H353K[/SUP] mouse that expresses a mouse-human hybrid form of the angiotensin-converting enzyme 2 (ACE2) receptor under the endogenous mouse Ace2 promoter, and a Rosa26 conditional knock-in mouse carrying the human ACE2 allele (Rosa26[SUP]hACE2[/SUP]). Although the mAce2[SUP]F83Y,H353K[/SUP] mice were susceptible to intranasal inoculation with SARS-CoV-2, they did not show gross phenotypic abnormalities. Next, we generated a Rosa26[SUP]hACE2[/SUP];CMV-Cre mouse line that ubiquitously expresses the human ACE2 receptor. By day 3 post infection with SARS-CoV-2, Rosa26[SUP]hACE2[/SUP];CMV-Cre mice showed significant weight loss, a variable degree of alveolar wall thickening and reduced survival rates. Viral load measurements confirmed inoculation in lung and brain tissues of infected Rosa26[SUP]hACE2[/SUP];CMV-Cre mice. The phenotypic spectrum displayed by our different mouse models translates to the broad range of clinical symptoms seen in the human patients and can serve as a resource for the community to model and explore both treatment strategies and long-term consequences of SARS-CoV-2 infection.
. 2024 Mar 15.
doi: 10.1007/s00335-024-10033-8. Online ahead of print. Generation of a humanized mAce2 and a conditional hACE2 mouse models permissive to SARS-COV-2 infection
I-Wen Song[SUP] 1 [/SUP], Megan Washington[SUP] 1 [/SUP], Carolina Leynes[SUP] 1 [/SUP], Jason Hsu[SUP] 2 [/SUP], Kempaiah Rayavara[SUP] 3 [/SUP], Yangjin Bae[SUP] 1 [/SUP], Nele Haelterman[SUP] 1 [/SUP], Yuqing Chen[SUP] 1 [/SUP], Ming-Ming Jiang[SUP] 1 [/SUP], Aleksandra Drelich[SUP] 3 [/SUP], Vivian Tat[SUP] 4 [/SUP], Denise G Lanza[SUP] 1 [/SUP], Isabel Lorenzo[SUP] 1 [/SUP], Jason D Heaney[SUP] 1 [/SUP], Chien-Te Kent Tseng[SUP] 3 [/SUP], Brendan Lee[SUP] 1 [/SUP], Ronit Marom[SUP] 5 [/SUP]
Affiliations
- PMID: 38488938
- DOI: 10.1007/s00335-024-10033-8
The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) remains a public health concern and a subject of active research effort. Development of pre-clinical animal models is critical to study viral-host interaction, tissue tropism, disease mechanisms, therapeutic approaches, and long-term sequelae of infection. Here, we report two mouse models for studying SARS-CoV-2: A knock-in mAce2[SUP]F83Y,H353K[/SUP] mouse that expresses a mouse-human hybrid form of the angiotensin-converting enzyme 2 (ACE2) receptor under the endogenous mouse Ace2 promoter, and a Rosa26 conditional knock-in mouse carrying the human ACE2 allele (Rosa26[SUP]hACE2[/SUP]). Although the mAce2[SUP]F83Y,H353K[/SUP] mice were susceptible to intranasal inoculation with SARS-CoV-2, they did not show gross phenotypic abnormalities. Next, we generated a Rosa26[SUP]hACE2[/SUP];CMV-Cre mouse line that ubiquitously expresses the human ACE2 receptor. By day 3 post infection with SARS-CoV-2, Rosa26[SUP]hACE2[/SUP];CMV-Cre mice showed significant weight loss, a variable degree of alveolar wall thickening and reduced survival rates. Viral load measurements confirmed inoculation in lung and brain tissues of infected Rosa26[SUP]hACE2[/SUP];CMV-Cre mice. The phenotypic spectrum displayed by our different mouse models translates to the broad range of clinical symptoms seen in the human patients and can serve as a resource for the community to model and explore both treatment strategies and long-term consequences of SARS-CoV-2 infection.