Evidence map›Paper›PMID 39287601›Full record

ArticleImmunoHorizons2024

Human ACE2 Gene Replacement Mice Support SARS-CoV-2 Viral Replication and Nonlethal Disease Progression.

Joshua M Thiede, Jenna K Dick, Nicholas N Jarjour, Venkatramana D Krishna, Lily Qian, Jules Sangala, Kellie Benzow, Kul Karanjeet, Shine Chin, Orion Rainwater and 6 more

Abstract read
In one paragraph

Article in ImmunoHorizons, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Joshua M ThiedeCenter for Immunology, University of Minnesota Medical School, Minneapolis, MN.ORCID 0000-0002-6603-281X
Jenna K DickCenter for Immunology, University of Minnesota Medical School, Minneapolis, MN.ORCID 0000-0003-2553-7536
Nicholas N JarjourCenter for Immunology, University of Minnesota Medical School, Minneapolis, MN.ORCID 0000-0001-9400-4448
Venkatramana D KrishnaDepartment of Veterinary Population Medicine, University of Minnesota College of Veterinary Medicine, St. Paul, MN.ORCID 0000-0002-1980-5525
Lily QianCenter for Immunology, University of Minnesota Medical School, Minneapolis, MN.ORCID 0000-0002-5114-4624
Jules SangalaCenter for Immunology, University of Minnesota Medical School, Minneapolis, MN.ORCID 0000-0002-6432-4966
Kellie BenzowDepartment of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MN.
Kul KaranjeetDepartment of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MN.
Shine ChinDepartment of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MN.
Orion RainwaterDepartment of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MN.ORCID 0000-0001-7402-2366
Maxim C-J CheeranDepartment of Veterinary Population Medicine, University of Minnesota College of Veterinary Medicine, St. Paul, MN.ORCID 0000-0002-5331-4746
Kristin A HogquistCenter for Immunology, University of Minnesota Medical School, Minneapolis, MN.
Stephen C JamesonCenter for Immunology, University of Minnesota Medical School, Minneapolis, MN.ORCID 0000-0001-9137-1146
Geoffrey T HartCenter for Immunology, University of Minnesota Medical School, Minneapolis, MN.ORCID 0000-0003-0483-307X
Tyler D BoldCenter for Immunology, University of Minnesota Medical School, Minneapolis, MN.
Michael D KoobDepartment of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MN.

Funding

T Cell HomeostasisR01AI038903 · NIAID · UNIVERSITY OF MINNESOTA TWIN CITIES · PI STEPHEN C JAMESON · 2001 to 2026
$5.9M
IMMUNOLOGY TRAINING PROGRAMT32AI007313 · NIAID · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Carla Rothlin · 1989 to 2026
$5.7M
NIAID NIH HHS R01 AI038903NIAID NIH HHS T32 AI007313
6 · The paper itself

Abstract

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.

Indexed as

Angiotensin-Converting Enzyme 2COVID-19Disease Models, AnimalDisease ProgressionSARS-CoV-2Virus ReplicationAnimalsHumansMiceMice, Inbred C57BLMice, TransgenicSpike Glycoprotein, CoronavirusACE2 protein, humanAce2 protein, mouseAngiotensin-Converting Enzyme 2Spike Glycoprotein, Coronavirus

Identifiers

PMID39287601
PMCPMC11447706

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.