生物资源2025，Vol.47Issue(6)：556-564,9.DOI:10.14188/j.ajsh.20250911001
一种对新冠病毒易感的全身性表达人源ACE2的小鼠模型
A systemic human ACE2-expressing mouse model susceptible to SARS-CoV-2
摘要
Abstract
This study introduces a novel mouse model—the systemic hACE2-luciferase transgenic mouse.This model,through the widespread expression of the human ACE2 receptor,exhibits high susceptibility to the original SARS-CoV-2 strain.Following infection with the original SARS-CoV-2 strain,the mice demonstrated a 100%mortal-ity rate within 6 days and presented notable infection symptoms.High viral loads(SARS-CoV-2 E gene,1010.59±0.27 copies/g)and severe pneumonia with neutrophil infiltration were detected in the lungs,alongside significant activa-tion of inflammatory signaling pathways such as NF-κB and tumor necrosis factor.After immunization with the mRNA vaccine,there was no significant difference in body weight between the immunized mice and the control group.Histo-pathological examination revealed only mild immune cell infiltration.The viral load in the lungs and brains of the mice was significantly reduced(the expression levels of the E gene in the lungs on days 6 and 14 post-infection were 105.24±0.26 copies/g and 105.32±0.17 copies/g,respectively),and complete avoidance of mortality was achieved.Further-more,infection with the SARS-CoV-2 Omicron BA.1 variant in this mouse model resulted in drastic body weight loss and was uniformly fatal within 10 days.The lungs exhibited high viral loads(SARS-CoV-2 E gene,108.25±0.07 copies/g)and severe pathological damage.In summary,this mouse model exhibited rapid weight loss,high mortality,and severe pulmonary pathological changes post-infection,demonstrating significant application value in assessing the pathological mechanisms of SARS-CoV-2 and the interventions of vaccines and therapeutic drugs.It represents a sys-temic human ACE2-expressing mouse model that is highly susceptible to SARS-CoV-2.关键词
新型冠状病毒/全身性表达hACE2小鼠/小鼠模型/疫苗评估Key words
SARS-CoV-2/systemic human ACE2-expressing mouse/mouse model/vaccine evaluation分类
医药卫生引用本文复制引用
陈菲,余唯艺,鲜巧阳,张贞,周立,王勇..一种对新冠病毒易感的全身性表达人源ACE2的小鼠模型[J].生物资源,2025,47(6):556-564,9.基金项目
国家重点研发计划(2022YFC2604100) （2022YFC2604100）
湖北省自然科学基金(2024AFB906) （2024AFB906）
