Animal models and experimental medicine最新文献

{"title":"Identification of ferroptosis-related genes involved in chronic obstructive pulmonary disease based on bioinformatics analysis.","authors":"Xuejing Luan, Jinghui Xie, Lu Zhang, Xiao Ma, Lichangtian Jiao, Jie Zhu","doi":"10.1002/ame2.70040","DOIUrl":"https://doi.org/10.1002/ame2.70040","url":null,"abstract":"<p><strong>Background: </strong>Chronic obstructive pulmonary disease (COPD) is a type of chronic respiratory disease. Studies confirmed that ferroptosis was involved in the progression of COPD, and its related mechanism is not clear. The aim of this study was to identify ferroptosis-related genes and reveal its pathological application in COPD.</p><p><strong>Methods: </strong>First, we downloaded two datasets from the Gene Expression Omnibus (GEO) to obtain the differential genes of COPD. Ferroptosis-related genes were obtained from the ferroptosis database, FerrDb. Next, we obtained the key genes in COPD rat to identify potential biomarkers using quantitative real-time polymerase chain reaction. Ferroptosis and inflammation were assessed using hematoxylin and eosin staining, lung function tests, and transmission electron microscopy (TEM).</p><p><strong>Results: </strong>These results were used to construct a COPD risk model with six key genes and explore the immunological characteristics of these genes. The resulting molecular subtype construction confirmed the importance of the key genes in COPD. Furthermore, we proved that ferroptosis occurred in the COPD rat model and identified the six key genes in rat lung tissue. TEM showed significant functional impairment and structural alterations in mitochondria, which is the key site of ferroptosis.</p><p><strong>Conclusion: </strong>Our COPD risk model, incorporating six key genes, highlighted their immunological roles in COPD using bioinformatics analysis and in vivo experiments. We hope to provide the basis for the treatment targeting ferroptosis in COPD.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144318934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pbs2 regulates late-stage macroautophagy in Saccharomyces cerevisiae.","authors":"Jianing Song, Haolin Zhang, Xingyu Cao, Zizhang Ren, Chao Tian, Miao Jia, Meiling Wu, Xiaoli Wang, Juan Wang","doi":"10.1002/ame2.70042","DOIUrl":"https://doi.org/10.1002/ame2.70042","url":null,"abstract":"<p><p>Autophagy is crucial for maintaining cellular homeostasis and is linked to various diseases. In Saccharomyces cerevisiae, the Polymyxin B Sensitivity 2 (Pbs2) protein is a member of the mitogen-activated protein kinase (MAPK) family and plays a role in mitophagy. To explore the potential role of Pbs2 in macroautophagy, we engineered wild-type and PBS2-deficient cells using plasmid construction and yeast transformation techniques, followed by a series of autophagy assays. First, after nitrogen starvation, the levels of autophagic activity were evaluated with the classical GFP-Atg8 cleavage assay and the Pho8Δ60 activity assay at different time points. Deleting PBS2 significantly decreased both GFP-Atg8 protein cleavage and Pho8Δ60 activity, indicating that Pbs2 is essential for macroautophagy. Furthermore, the influence of Pbs2 on macroautophagy was shown to be independent of Hog1, a well-known downstream factor of Pbs2. Second, the Atg8 lipidation assay demonstrated that Atg8 lipidation levels increased upon PBS2 deletion, suggesting that Pbs2 acts after Atg8 lipidation. Third, the proteinase K protection assay indicated that the loss of PBS2 led to a higher proportion of closed autophagosomes, implying that Pbs2 impacts the later stages of macroautophagy following autophagosome closure. In conclusion, Pbs2 regulates the late stages of macroautophagy induced by nitrogen starvation.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SOX6 enhances vascular smooth muscle cell phenotypic switching and elevates blood pressure by activating autophagy.","authors":"Qianhui Ling, Xilan Dong, Liyan Mao, Chengjun Huang, Linjing Cong, Haizeng Zhang, Jun Cai, Zhenzhen Chen","doi":"10.1002/ame2.70046","DOIUrl":"https://doi.org/10.1002/ame2.70046","url":null,"abstract":"<p><strong>Background: </strong>SOX6 has been shown to play a crucial role in the development of the cardiovascular system. However, its potential role in hypertension and vascular function remains unclear.</p><p><strong>Methods: </strong>In vascular smooth muscle cells (VSMCs), we employed gain- and loss-of-function approaches combined with RNA sequencing, autophagy flux assessment, and phenotype characterization. Additionally, we established a mouse model with Sox6 overexpression via adeno-associated virus 2 (AAV2) to validate the findings in vivo.</p><p><strong>Results: </strong>We validated the increased expression of SOX6 in hypertension both in vitro and in vivo. Genetic silencing of Sox6 in VSMCs attenuated the phenotypic switching induced by angiotensin II. Conversely, in vivo overexpression of Sox6 led to a significant elevation in blood pressure and promoted vascular remodeling. Mechanistically, SOX6 was shown to regulate phenotypic switching via an autophagy-dependent pathway. Specifically, Sox6 overexpression augmented VSMC autophagy and facilitated phenotypic switching, whereas Sox6 knockdown yielded opposite outcomes. Modulation of autophagy using 3-MA or RAPA could effectively counteract the effect mediated by SOX6.</p><p><strong>Conclusions: </strong>Our findings revealed that SOX6 regulates VSMC plasticity and elevates blood pressure by activating autophagy. Therefore, SOX6 inhibition potentially represents a novel strategy for treating hypertension and vascular remodeling.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144276949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Time- and dose-related pathological changes in knee osteoarthritis rat model induced by monosodium iodoacetate.","authors":"Wei Pu, Qi Liu, Shuyan Xue, Siyuan Li, Nan Nan, Yang Liu, Huiqin Hao","doi":"10.1002/ame2.70037","DOIUrl":"https://doi.org/10.1002/ame2.70037","url":null,"abstract":"<p><p>Knee osteoarthritis (KOA) is a chronic degenerative disease. Monosodium iodoacetate (MIA) induction is the most commonly used therapeutic effect evaluation and mechanism of action research model; we observed a lack of standardization and uniformity in current model building methods, which led us to conduct this study.</p><p><strong>Background: </strong>The aim was to investigate the time- and dose-related changes in the behavioral and pathological characteristics in the MIA-induced KOA model rat.</p><p><strong>Methods: </strong>MIA (40, 50, and 60 mg/mL) was injected into the left joint of male Sprague-Dawley rats. After 2 weeks, the changes in the KOA rat model were observed by behavioral evaluation, imaging-level evaluation, and histological-level evaluation. The changes were also compared after 40-mg/mL MIA injection for 2 and 6 weeks.</p><p><strong>Results: </strong>MIA-induced bone surface defects, osteophyte hyperplasia around the articular rim, increased subchondral bone density, thinning of the sparse trabecular bone, structural disorder, and local clustering were observed. The degree of injury gradually increased with the increase in MIA concentration. After 6 weeks, subchondral bone density and sparse trabecular bone increased in the KOA model.</p><p><strong>Conclusions: </strong>The severity of the model also increased significantly with the changes in dose and time. In dose-dependent experiments, this study revealed that 40 mg/mL was the optimal dose to induce significant pathological changes without causing undue discomfort or death in animals. This dose may induce pathological changes stably and is suitable for long-term observation.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144276950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in CRISPR-Cas9 in lineage tracing of model animals","authors":"Jingchao Cao,&nbsp;Zihang Guo,&nbsp;Xueling Xu,&nbsp;Pan Li,&nbsp;Yi Fang,&nbsp;Shoulong Deng","doi":"10.1002/ame2.70033","DOIUrl":"10.1002/ame2.70033","url":null,"abstract":"<p>Cell lineage tracing is a key technology for describing the developmental history of individual progenitor cells and assembling them to form a lineage development tree. However, traditional methods have limitations of poor stability and insufficient resolution. As an efficient and flexible gene editing tool, CRISPR-Cas9 system has been widely used in biological research. Furthermore, CRISPR-Cas9 gene editing-based tracing methods can introduce fluorescent proteins, reporter genes, or DNA barcodes for high-throughput sequencing, enabling precise lineage analysis, significantly improving precision and resolution, and expanding its application range. In this review, we summarize applications of CRISPR-Cas9 system in cell lineage tracing, with special emphasis on its successful applications in traditional model animals (e.g., zebrafish and mice), large animal models (pigs), and human cells or organoids. We also discussed its potential prospects and challenges in xenotransplantation and regenerative medicine.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"8 6","pages":"1004-1022"},"PeriodicalIF":0.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ame2.70033","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Respiratory virus mRNA vaccines: mRNA Design, clinical studies, and future challenges.","authors":"Linlin Zheng, Han Feng","doi":"10.1002/ame2.70018","DOIUrl":"https://doi.org/10.1002/ame2.70018","url":null,"abstract":"<p><p>Respiratory infectious diseases frequently erupt on a global scale, with RNA viruses, such as SARS-CoV-2, RSV, and influenza viruses, posing challenges to vaccine development due to their high mutation rates. Traditional vaccine development cycles are lengthy and struggle to keep pace with rapidly evolving viruses, whereas messenger RNA (mRNA) vaccines have demonstrated significant advantages due to their short development periods, straightforward production, and low costs. After the outbreak of the COVID-19 pandemic, multiple mRNA vaccines, including Pfizer-BioNTech and Moderna, rapidly received emergency use authorization, validating their feasibility. The Nobel Prize in Physiology or Medicine in 2023 was awarded to Katalin Karikó and Drew Weissman, underscoring the efficacy of mRNA vaccine technology. In 2024, the U.S. Food and Drug Administration (FDA) approval of Moderna's respiratory syncytial virus (RSV) mRNA vaccine marked the immense potential of mRNA technology in vaccine innovation. This review article summarizes the design, clinical research, and future challenges of mRNA vaccines for respiratory viruses, delving into antigen design, mRNA delivery systems, and advancements in vaccines for multiple respiratory viruses, including innovations in self-amplifying mRNA and circular mRNA vaccines. Additionally, the development of combination vaccines is underway, aiming to provide protection against multiple viruses through a single administration. Despite the significant progress in mRNA vaccine development, challenges remain regarding raw material costs, stability, and delivery efficiency. In the future, with technological advancements and the accumulation of clinical experience, the design strategies and delivery systems of mRNA vaccines are expected to be continuously optimized, thereby enhancing their safety and efficacy.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144227932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A hepatoprotective experiment on taro vegetable (Colocasia esculenta (L.) Schott) flower employing animal models by mitigating oxidative stress.","authors":"Mahathir Mohammad, Fahmida Tasnim Richi, Rabiul Hossain, Md Arafat, Pair Ahmed Jiko, Nazim Uddin Emon, Sayed Al Hossain Rabbi, Tirtha Khastagir, Md Hemayet Hossain, Safaet Alam","doi":"10.1002/ame2.70031","DOIUrl":"https://doi.org/10.1002/ame2.70031","url":null,"abstract":"<p><strong>Background: </strong>Colocasia esculenta (L.) Schott, known as the taro vegetable, possesses various beneficial effects and is traditionally used in folk medicine. This study explores the ameliorative antioxidant and hepatoprotective effect of a methanolic extract of the C. esculenta flower (ME-CEF) against oxidative damage and hepatotoxicity in mice.</p><p><strong>Methods: </strong>The antioxidant efficacy of ME-CEF was assessed using 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging assay. The hepatoprotective effect was investigated by an assessment of liver injury indicators (amino transferase [ALT], aspartate amino transferase [AST], alkaline phosphatase [ALP], bilirubin, creatinine) and normalizing lipid profiles (cholesterol [CHO], triglyceride [TG], high-density lipoprotein [HDL], and low-density lipoprotein [LDL]) along with histopathological study and antioxidant enzymes (CAT). A phytochemical analysis, both qualitative and quantitative, was conducted, including gas chromatography-tandem mass spectrometry (GC-MS/MS) analysis and an in silico molecular docking study.</p><p><strong>Results: </strong>The Result Showed that ME-CEF Possesses Moderate ABTS and DPPH Scavenging Activity with IC₅₀ Values of 117.18 and 160.41 μg/mL. As Illustrated by Reducing Liver Enzymes (ALT, AST, ALP, Bilirubin, Creatinine) and Lipid Profile (CHO, TG, LDL) and Raising HDL Levels (p < 0.01), ME-CEF Dose Dependently Mitigated CCl₄-Induced Acute Liver Injury. Furthermore, ME-CEF Blocked Hepatic Oxidative Stress by Boosting Antioxidant Enzymes (CAT) and Preventing Liver Tissue Damage and Apoptosis. In Silico Investigations Also Showed a Promising Binding Affinity with Tumor Necrosis Factor α (TNF-α), Interleukin 6 (IL-6), PRAP-1, and Xanthin Oxidoreductase, which Displayed Antioxidant and Hepatoprotective Candidacy while Notable Safety and Efficacy Profile Was Also Documented through ADME/T Studies. Histopathological Analysis Showed Reduced Hepatocellular Necrosis and Vascular Congestion in Silymarin and Extract Groups.</p><p><strong>Conclusion: </strong>Based on these results, our findings strongly recommend the medicinal use of the plant, highlighting its antioxidant and hepatoprotective potentials.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144176310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bifidobacterium animalis subsp. lactis modulates early-life immune response and gut metabolism","authors":"Haoming Du,&nbsp;Yiran Cai,&nbsp;Lulu Shen,&nbsp;Yuxing Zheng,&nbsp;Lingling Zhao,&nbsp;Ruibiao Hu,&nbsp;Shan Jiang,&nbsp;Jiajia Yuan,&nbsp;Chengming Hu,&nbsp;Qi Deng,&nbsp;Jiaoyan Huang,&nbsp;Jingbo Hu,&nbsp;Yuexiang Wang,&nbsp;Jing Tan,&nbsp;Jiahui Chen,&nbsp;Feitong Liu,&nbsp;Yuanyuan Duan,&nbsp;Haitao Niu","doi":"10.1002/ame2.70034","DOIUrl":"10.1002/ame2.70034","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The maturation of the immune system is critical during early life, as it involves the differentiation, maturation, and establishment of immune tolerance of immune cells. This process is influenced not only by genetic factors but also by environmental factors, particularly the symbiotic microbiota. <i>Bifidobacterium animalis</i> subsp. lactis (BB-12), originally found in dairy products, is widely used in infant formula and dietary supplements. However, its role and mechanisms in immune development during early life remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using GF mice as the experimental model, <i>B. animalis</i> subsp. lactis BB-12 was administered via gavage during early life. In the juvenile stage, changes in T-cell subsets in the spleen, thymus, and gut intraepithelial lymphocytes (IEL) were assessed using spectral flow cytometry. Additionally, targeted metabolomics analysis of tryptophan metabolism and short-chain fatty acid pathways in colonic tissue was conducted to explore how <i>B. animalis</i> subsp. lactis BB-12 influences the immune system through gut microbiota metabolism.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>BB-12 effectively modulates the gut immune microenvironment, leading to beneficial changes in T-cell subsets in key immune tissues such as the spleen, thymus, and gut IELs. Metabolomics analysis further supports these findings by showing that BB-12 intervention greatly increased the production of tryptophan derivatives and acetic acid in the colon of GF mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The findings provide theoretical evidence for the role of <i>B. animalis</i> subsp. lactis in immune system development and support its application in dietary supplements, suggesting potential as a component for infant immune health and in preventing immune-related diseases.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"8 6","pages":"965-976"},"PeriodicalIF":0.0,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ame2.70034","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144176328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A mouse model of lung ischemia-reperfusion injury with reversible left hilar entrapment.","authors":"GuangDong Weng, Yao Chen, ShanQing Bao, ChengXin Zhang, WenHui Gong","doi":"10.1002/ame2.70030","DOIUrl":"https://doi.org/10.1002/ame2.70030","url":null,"abstract":"<p><p>Lung ischemia-reperfusion injury (LIRI), an acute lung injury syndrome triggered by lung transplantation or distal organ ischemia, has long been a difficult and hot issue in clinical research. In this study, we proposed a simple and less invasive reversible LIRI surgical protocol, achieved by improving the mouse left hilar entrapment model, which significantly improved the operability of the experiment and the reproducibility of the results. The protocol achieves precise control of the ischemic and reperfusion processes by visualizing transoral intubation, using reversible ligation of live knots to clamp the left hilar, and temporary closure of the thoracic cavity during ischemia. The reversible survival model we constructed not only provides a reliable tool to study the cellular and molecular mechanisms of LIRI but also can be used to assess the stage of injury regression, experimental pneumonia, and survival in mice. In addition, it simplifies the lung portal separation clamping operation for reversible clamping and provides an easy-to-learn visual tracheal intubation method that can be quickly mastered and replicated by beginners for consistent and reliable results.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144153056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of the pathogenicity of multiple SARS-CoV-2 variants in mouse models.","authors":"Qi Lv, Ming Liu, Feifei Qi, Mingya Liu, Fengdi Li, Ran Deng, Xujian Liang, Yanfeng Xu, Zhiqi Song, Yiwei Yan, Shuyue Li, Guocui Mou, Linlin Bao","doi":"10.1002/ame2.70029","DOIUrl":"https://doi.org/10.1002/ame2.70029","url":null,"abstract":"<p><strong>Background: </strong>New variants of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)continue to drive global epidemics and pose significant health risks. The pathogenicity of these variants evolves under immune pressure and host factors. Understanding these changes is crucial for epidemic control and variant research.</p><p><strong>Methods: </strong>Human angiotensin-converting enzyme 2(hACE2) transgenic mice were intranasally challenged with the original strain WH-09 and the variants Delta, Beta, and Omicron BA.1, while BALB/c mice were challenged with Omicron subvariants BA.5, BF.7, and XBB.1. To compare the pathogenicity differences among variants, we conducted a comprehensive analysis that included clinical symptom observation, measurement of viral loads in the trachea and lungs, evaluation of pulmonary pathology, analysis of immune cell infiltration, and quantification of cytokine levels.</p><p><strong>Results: </strong>In hACE2 mice, the Beta variant caused significant weight loss, severe lung inflammation, increased inflammatory and chemotactic factor secretion, greater macrophage and neutrophil infiltration in the lungs, and higher viral loads with prolonged shedding duration. In contrast, BA.1 showed a significant reduction in pathogenicity. The BA.5, BF.7, and XBB.1 variants were less pathogenic than the WH-09, Beta, and Delta variants when infected in BALB/c mice. This was evidenced by reduced weight loss, diminished pulmonary pathology, decreased secretion of inflammatory factors and chemokines, reduced macrophage and neutrophil infiltration, as well as lower viral loads in both the trachea and lungs.</p><p><strong>Conclusion: </strong>In hACE2 mice, the Omicron variant demonstrated the lowest pathogenicity, while the Beta variant exhibited the highest. Pathogenicity of the Delta variant was comparable to the original WH-09 strain. Among BALB/c mice, Omicron subvariants BA.5, BF.7, and XBB.1 showed no statistically significant differences in virulence.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}