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

Q3 Medicine ImmunoHorizons Pub Date : 2024-09-01 DOI:10.4049/immunohorizons.2400030
Joshua M Thiede, Jenna K Dick, Nicholas N Jarjour, Venkatramana D Krishna, Lily Qian, Jules Sangala, Kellie Benzow, Kul Karanjeet, Shine Chin, Orion Rainwater, Maxim C-J Cheeran, Kristin A Hogquist, Stephen C Jameson, Geoffrey T Hart, Tyler D Bold, Michael D Koob
{"title":"Human ACE2 Gene Replacement Mice Support SARS-CoV-2 Viral Replication and Nonlethal Disease Progression.","authors":"Joshua M Thiede, Jenna K Dick, Nicholas N Jarjour, Venkatramana D Krishna, Lily Qian, Jules Sangala, Kellie Benzow, Kul Karanjeet, Shine Chin, Orion Rainwater, Maxim C-J Cheeran, Kristin A Hogquist, Stephen C Jameson, Geoffrey T Hart, Tyler D Bold, Michael D Koob","doi":"10.4049/immunohorizons.2400030","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"8 9","pages":"712-720"},"PeriodicalIF":0.0000,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447706/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ImmunoHorizons","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.4049/immunohorizons.2400030","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 0

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.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
人类 ACE2 基因替代小鼠支持 SARS-CoV-2 病毒复制和非致命性疾病进展。
许多 SARS-CoV-2 感染小鼠模型都涉及在小鼠组织中表达人 ACE2 蛋白,即 SARS-CoV-2 Spike 蛋白的进入受体。然而,这些模型中的大多数都存在 ACE2 表达的非生理性调节问题,这可能会导致非典型的严重感染和异常的病毒复制位点。在本报告中,我们开发并鉴定了一种 ACE2 基因替代(ACE2-GR)小鼠品系,在该品系中,小鼠 Ace2 基因组位点被整个人类 ACE2 基因位点所替代,我们还研究了这些动物对 SARS-CoV-2 感染的反应能力。我们的研究表明,ACE2-GR 小鼠支持 SARS-CoV-2 病毒复制,但与广泛使用的 K18-hACE2 转基因模型形成鲜明对比的是,这种感染导致的疾病较轻,中枢神经系统未受影响。因此,据我们所知,ACE2-GR 小鼠为探索 SARS-CoV-2 感染的免疫反应和长期后果提供了一种新的模型。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
CiteScore
3.70
自引率
0.00%
发文量
0
审稿时长
4 weeks
期刊最新文献
Comparison of B Cell Variable Region Gene Segment Characteristics in Neuro-autoantibodies. α-Hemolysin from Staphylococcus aureus Changes the Epigenetic Landscape of Th17 Cells. Estimates of Sequences with Ultralong and Short CDR3s in the Bovine IgM B Cell Receptor Repertoire Using the Long-read Oxford Nanopore MinION Platform. Improving Reliability of Immunological Assays by Defining Minimal Criteria for Cell Fitness. Bruton Tyrosine Kinase Inhibition Decreases Inflammation and Differentially Impacts Phagocytosis and Cellular Metabolism in Mouse- and Human-derived Myeloid Cells.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1