TY - JOUR
T1 - Human ACE2 Gene Replacement Mice Support SARS-CoV-2 Viral Replication and Nonlethal Disease Progression
AU - Thiede, Joshua M.
AU - Dick, Jenna K.
AU - Jarjour, Nicholas N.
AU - Krishna, Venkatramana D.
AU - Qian, Lily
AU - Sangala, Jules
AU - Benzow, Kellie
AU - Karanjeet, Kul
AU - Chin, Shine
AU - Rainwater, Orion
AU - Cheeran, Maxim C.J.
AU - Hogquist, Kristin A.
AU - Jameson, Stephen C.
AU - Hart, Geoffrey T.
AU - Bold, Tyler D.
AU - Koob, Michael D.
N1 - Publisher Copyright:
Copyright © 2024 The Authors.
PY - 2024/9/1
Y1 - 2024/9/1
N2 - Many mouse models of SARS-CoV-2 infection involve expression of the human ACE2 protein, the entry receptor for SARS-CoV-2 Spike protein, in mouse tissues. However, most of these models suffer from nonphysiological regulation of ACE2 expression, which can lead to atypically severe infections and aberrant sites of viral replication. In this report, we developed and characterized an ACE2 gene replacement (ACE2-GR) mouse strain in which the mouse Ace2 genomic locus was replaced by the entire human ACE2 gene locus, and we investigated the ability of these animals to respond to SARS-CoV-2 infection. We show that ACE2-GR mice support SARS-CoV-2 viral replication, but, in stark contrast to the widely used K18-hACE2 transgenic model, this infection leads to a mild disease with no detectable involvement of the CNS. Thus, ACE2-GR mice provide a novel, to our knowledge, model to explore immune responses and long-term consequences of SARS-CoV-2 infection.
AB - Many mouse models of SARS-CoV-2 infection involve expression of the human ACE2 protein, the entry receptor for SARS-CoV-2 Spike protein, in mouse tissues. However, most of these models suffer from nonphysiological regulation of ACE2 expression, which can lead to atypically severe infections and aberrant sites of viral replication. In this report, we developed and characterized an ACE2 gene replacement (ACE2-GR) mouse strain in which the mouse Ace2 genomic locus was replaced by the entire human ACE2 gene locus, and we investigated the ability of these animals to respond to SARS-CoV-2 infection. We show that ACE2-GR mice support SARS-CoV-2 viral replication, but, in stark contrast to the widely used K18-hACE2 transgenic model, this infection leads to a mild disease with no detectable involvement of the CNS. Thus, ACE2-GR mice provide a novel, to our knowledge, model to explore immune responses and long-term consequences of SARS-CoV-2 infection.
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U2 - 10.4049/immunohorizons.2400030
DO - 10.4049/immunohorizons.2400030
M3 - Article
C2 - 39287601
AN - SCOPUS:85204418695
SN - 2573-7732
VL - 8
SP - 712
EP - 720
JO - ImmunoHorizons
JF - ImmunoHorizons
IS - 9
ER -