Pub Date : 2025-12-01Epub Date: 2025-12-09DOI: 10.1002/ame2.70114
Yu Peng, Ying Zhang, Shenhui Yang, Lu He, Shuangxi Chen
Background: Brachial plexus root avulsion (BPRA), a well-known form of peripheral nerve injury, results in motor function loss in the affected forelimb due to motoneuron (MN) death, which may be influenced by neuroinflammation following a lesion in the spinal cord. Although synthase-stimulator of interferon genes (STING) signaling can contribute to chronic inflammation and tissue damage in a number of pathological conditions, the essential role of STING signaling in BPRA remains to be reported. Based on our previous findings that the STING mRNA level is upregulated in the anterior horn of the segment of the affected spinal cords of mice with BPRA, STING may be associated with motor recovery in BPRA.
Methods: In the present study, STING knockout transgenic mice were used to establish a BPRA re-implantation model, which was followed by behavioral tests, histochemical staining and quantitative reverse transcription polymerase chain reaction.
Results: The results demonstrated that STING deficiency can increase the body weight, promote motor recovery, decrease MN death, inhibit pyroptosis and neuroinflammation, increase remyelination, and reduce the atrophy of the biceps brachii in mice with BPRA.
Conclusion: These combined results suggest that inhibition of STING may be a promising strategy for treating BPRA.
{"title":"STING deficiency promotes motor recovery in mice following brachial plexus root avulsion.","authors":"Yu Peng, Ying Zhang, Shenhui Yang, Lu He, Shuangxi Chen","doi":"10.1002/ame2.70114","DOIUrl":"10.1002/ame2.70114","url":null,"abstract":"<p><strong>Background: </strong>Brachial plexus root avulsion (BPRA), a well-known form of peripheral nerve injury, results in motor function loss in the affected forelimb due to motoneuron (MN) death, which may be influenced by neuroinflammation following a lesion in the spinal cord. Although synthase-stimulator of interferon genes (STING) signaling can contribute to chronic inflammation and tissue damage in a number of pathological conditions, the essential role of STING signaling in BPRA remains to be reported. Based on our previous findings that the STING mRNA level is upregulated in the anterior horn of the segment of the affected spinal cords of mice with BPRA, STING may be associated with motor recovery in BPRA.</p><p><strong>Methods: </strong>In the present study, STING knockout transgenic mice were used to establish a BPRA re-implantation model, which was followed by behavioral tests, histochemical staining and quantitative reverse transcription polymerase chain reaction.</p><p><strong>Results: </strong>The results demonstrated that STING deficiency can increase the body weight, promote motor recovery, decrease MN death, inhibit pyroptosis and neuroinflammation, increase remyelination, and reduce the atrophy of the biceps brachii in mice with BPRA.</p><p><strong>Conclusion: </strong>These combined results suggest that inhibition of STING may be a promising strategy for treating BPRA.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":"2222-2231"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12884437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145717033","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}
Pub Date : 2025-12-01Epub Date: 2025-06-17DOI: 10.1002/ame2.70040
Xuejing Luan, Jinghui Xie, Lu Zhang, Xiao Ma, Lichangtian Jiao, Jie Zhu
Background: 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.
Methods: 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).
Results: 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.
Conclusion: 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.
背景:慢性阻塞性肺疾病(COPD)是一种慢性呼吸系统疾病。研究证实,铁下垂参与COPD的发展,其相关机制尚不清楚。本研究的目的是鉴定铁沉相关基因并揭示其在COPD中的病理应用。方法:首先,我们从Gene Expression Omnibus (GEO)下载两个数据集,获取COPD的差异基因。从铁中毒数据库FerrDb中获得铁中毒相关基因。接下来,我们获得COPD大鼠的关键基因,利用实时定量聚合酶链反应鉴定潜在的生物标志物。通过苏木精和伊红染色、肺功能检查和透射电镜(TEM)评估铁下垂和炎症。结果:利用这些结果构建了包含6个关键基因的COPD风险模型,并探讨了这些基因的免疫学特征。由此产生的分子亚型构建证实了关键基因在COPD中的重要性。此外,我们证实了在COPD大鼠模型中发生铁下垂,并鉴定了大鼠肺组织中的6个关键基因。透射电镜显示,线粒体是铁下垂的关键部位,其功能损伤和结构改变明显。结论:我们的COPD风险模型包含6个关键基因,通过生物信息学分析和体内实验,突出了它们在COPD中的免疫作用。希望为COPD患者铁下垂的靶向治疗提供依据。
{"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":"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":"2232-2252"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12884441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144318934","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}
Pub Date : 2025-12-01Epub Date: 2026-01-07DOI: 10.1002/ame2.70135
Rodel Jonathan S Vitor, John Sylvester B Nas, Bryan John A Magoling, Frances C Recuenco, Sharon Yvette Angelina M Villanueva, Catherine T Albano, Delwin D Capuyo, Sebastian Jose David, Ma Danica Ines-Ramil, Alisha Wehdnesday B Reyes, Cherry P Fernandez-Colorado
As the Philippines celebrated the 2nd Asia Laboratory Animal Day (ALAD) last November 29, 2025, the Philippine Association for Laboratory Animal Sciences (PALAS) reflected on a year marked by growth, collaboration, and renewed commitment to ethical and scientific excellence in animal-based research. Throughout 2025, PALAS has continued to strengthen the laboratory animal science community by advancing education, capacity building, policy advocacy, and regional cooperation. These efforts underscore PALAS' vital role in shaping a culture of responsible animal research aligned with international standards.
{"title":"Advancing laboratory animal science in the Philippines: PALAS initiatives and partnerships leading to Asia Laboratory Animal Day 2025.","authors":"Rodel Jonathan S Vitor, John Sylvester B Nas, Bryan John A Magoling, Frances C Recuenco, Sharon Yvette Angelina M Villanueva, Catherine T Albano, Delwin D Capuyo, Sebastian Jose David, Ma Danica Ines-Ramil, Alisha Wehdnesday B Reyes, Cherry P Fernandez-Colorado","doi":"10.1002/ame2.70135","DOIUrl":"10.1002/ame2.70135","url":null,"abstract":"<p><p>As the Philippines celebrated the 2nd Asia Laboratory Animal Day (ALAD) last November 29, 2025, the Philippine Association for Laboratory Animal Sciences (PALAS) reflected on a year marked by growth, collaboration, and renewed commitment to ethical and scientific excellence in animal-based research. Throughout 2025, PALAS has continued to strengthen the laboratory animal science community by advancing education, capacity building, policy advocacy, and regional cooperation. These efforts underscore PALAS' vital role in shaping a culture of responsible animal research aligned with international standards.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":"2184-2186"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12884435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145919346","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}
Pub Date : 2025-12-01Epub Date: 2026-01-08DOI: 10.1002/ame2.70136
John Shia Kwong Siew
Malaysia's commemoration of the second Asia Laboratory Animal Day (ALAD) in 2025 marked a notable step forward in strengthening national and regional laboratory animal science, ethical governance, and humane research practices. Celebrated a day earlier on 28 November, an initiative led by the Laboratory Animal Science Association of Malaysia (LASAM), comprised a coordinated three-month programme from September to November. A series of targeted activities were conducted, including professional exchange visits, competency-based rodent care and use workshops, refinement-centred blood sampling training, and institutional lectures on ethics and welfare. These engagements involved researchers, technicians, ethics committee members, and undergraduate trainees; reflecting ALAD's aim of fostering ethical awareness and technical proficiency across all levels of research personnel. A major highlight of the campaign was the signing of a Memorandum of Understanding between LASAM and Universiti Teknologi MARA (UiTM), strengthening long-term collaboration in training, welfare standard harmonisation, and shared ethical governance. The programme also delivered measurable outcomes: over 92% of participants improved their understanding of the 3Rs and humane endpoints, more than 95% attained competency in basic rodent handling, and national interest in laboratory animal science increased, as reflected by rising LASAM membership. Malaysia's ALAD initiatives emphasise the importance of grassroots engagement, refinement-based training, and strong institutional partnerships in advancing ethical and humane science. The country's experience provides a replicable framework for other Asian regions seeking to enhance welfare capacity, harmonise standards, and cultivate responsible research communities. Malaysia remains committed to supporting ALAD's ongoing mission to advance scientific integrity and animal welfare across Asia.
{"title":"Malaysia's commemorative activities for the second Asia Laboratory Animal Day (ALAD).","authors":"John Shia Kwong Siew","doi":"10.1002/ame2.70136","DOIUrl":"10.1002/ame2.70136","url":null,"abstract":"<p><p>Malaysia's commemoration of the second Asia Laboratory Animal Day (ALAD) in 2025 marked a notable step forward in strengthening national and regional laboratory animal science, ethical governance, and humane research practices. Celebrated a day earlier on 28 November, an initiative led by the Laboratory Animal Science Association of Malaysia (LASAM), comprised a coordinated three-month programme from September to November. A series of targeted activities were conducted, including professional exchange visits, competency-based rodent care and use workshops, refinement-centred blood sampling training, and institutional lectures on ethics and welfare. These engagements involved researchers, technicians, ethics committee members, and undergraduate trainees; reflecting ALAD's aim of fostering ethical awareness and technical proficiency across all levels of research personnel. A major highlight of the campaign was the signing of a Memorandum of Understanding between LASAM and Universiti Teknologi MARA (UiTM), strengthening long-term collaboration in training, welfare standard harmonisation, and shared ethical governance. The programme also delivered measurable outcomes: over 92% of participants improved their understanding of the 3Rs and humane endpoints, more than 95% attained competency in basic rodent handling, and national interest in laboratory animal science increased, as reflected by rising LASAM membership. Malaysia's ALAD initiatives emphasise the importance of grassroots engagement, refinement-based training, and strong institutional partnerships in advancing ethical and humane science. The country's experience provides a replicable framework for other Asian regions seeking to enhance welfare capacity, harmonise standards, and cultivate responsible research communities. Malaysia remains committed to supporting ALAD's ongoing mission to advance scientific integrity and animal welfare across Asia.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":"2180-2183"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12884429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145919382","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}
Background: Alzheimer's disease (AD) represents the most prevalent neurodegenerative disorder, with mitochondrial dysfunction being observed in both AD patients and mouse models. Nonetheless, further investigation is required to elucidate the pathogenic genes associated with AD and to develop early diagnostic methodologies centered on mitochondrial function.
Methods: In this study, the dataset GSE132903 was retrieved from the GEO database, encompassing both non-demented (ND) control and AD samples. Through the combination of differential expression gene analysis, weighted gene co-expression network analysis, and intersection with mitochondrial database gene sets, four hub genes associated with AD were identified. These four hub genes were subsequently validated in APP/PS1 and 5xFAD mouse models using molecular biology techniques.
Results: The hub genes identified through bioinformatics analysis include SYNJ2BP, VDAC1, NUBPL, and COX19. Within the GSE132903 dataset, the expression levels of SYNJ2BP, NUBPL, and COX19 were significantly elevated in the AD group compared to the non-demented (ND) group, whereas VDAC1 expression was reduced in the AD group relative to the ND group. Furthermore, in the hippocampus of APP/PS1 and 5xFAD mouse models, the expression patterns of SYNJ2BP and NUBPL were consistent with the bioinformatics analysis results.
Conclusion: Hub genes identified here through bioinformatics and molecular biology may help early diagnosis of AD patients and may also help build new AD models to explore its pathogenesis.
{"title":"Hub genes and diagnostic model associated with mitochondrial function in Alzheimer's disease.","authors":"Xuchao Zhu, Ling Zhang, Chuan Qin","doi":"10.1002/ame2.70104","DOIUrl":"https://doi.org/10.1002/ame2.70104","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) represents the most prevalent neurodegenerative disorder, with mitochondrial dysfunction being observed in both AD patients and mouse models. Nonetheless, further investigation is required to elucidate the pathogenic genes associated with AD and to develop early diagnostic methodologies centered on mitochondrial function.</p><p><strong>Methods: </strong>In this study, the dataset GSE132903 was retrieved from the GEO database, encompassing both non-demented (ND) control and AD samples. Through the combination of differential expression gene analysis, weighted gene co-expression network analysis, and intersection with mitochondrial database gene sets, four hub genes associated with AD were identified. These four hub genes were subsequently validated in APP/PS1 and 5xFAD mouse models using molecular biology techniques.</p><p><strong>Results: </strong>The hub genes identified through bioinformatics analysis include SYNJ2BP, VDAC1, NUBPL, and COX19. Within the GSE132903 dataset, the expression levels of SYNJ2BP, NUBPL, and COX19 were significantly elevated in the AD group compared to the non-demented (ND) group, whereas VDAC1 expression was reduced in the AD group relative to the ND group. Furthermore, in the hippocampus of APP/PS1 and 5xFAD mouse models, the expression patterns of SYNJ2BP and NUBPL were consistent with the bioinformatics analysis results.</p><p><strong>Conclusion: </strong>Hub genes identified here through bioinformatics and molecular biology may help early diagnosis of AD patients and may also help build new AD models to explore its pathogenesis.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145643772","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}
Background: The golden Syrian hamster is a valuable animal model for studying carcinogenesis, metabolic disorders, cardiovascular diseases, and viral infections due to its biological and pathological similarities to humans. However, the development of genetically engineered hamsters has lagged behind that of mice and rats, largely because of an embryonic development block at the two-cell stage in vitro. Although CRISPR/Cas9-mediated gene knockout has been achieved in hamsters, precise DNA fragment insertion or conditional knockout (cKO) models have not previously been reported, likely due to technical limitations in embryo manipulation and insufficient efficiency of homology-directed repair (HDR).
Methods: In this study, we generated conditional alleles of the ApoF gene in golden Syrian hamsters. A two-cut strategy was applied using Cas9 protein, two sgRNAs, and a single donor plasmid containing exon 2 flanked by loxP sites and two ~0.8 kb homology arms. A mixture of Cas9 protein, sgRNAs, and the donor plasmid was microinjected into the pronuclei of one-cell stage hamster embryos.
Results: The efficiency of CRISPR/Cas9-mediated loxP knock-in reached up to 27%, and the genetically modified floxed alleles were successfully transmitted through the germline. The functionality of the inserted loxP sites was validated by in vivo Cre-mediated recombination following local administration of AAV vectors, including AAV-cTnT-Cre in the heart and AAV-CMV-Cre in the brain.
Conclusions: To our knowledge, this work represents the first successful establishment of a conditional knockout model in the golden Syrian hamster, providing a valuable tool for mechanistic studies of gene function and disease modeling.
{"title":"Generating golden Syrian hamsters with conditional alleles via zygote microinjection of CRISPR/Cas9.","authors":"Wei Chen, Xu Zhang, Rui Fan, Xia Li, Feifei Guan, Gefan Wan, Weining Kong, Xiaolong Qi, Shuo Pan, Sijing Shi, Yuanlong Su, Shan Gao, Wei Huang, Xunde Xian, Jiangning Liu, Yuhui Wang, Yuanwu Ma","doi":"10.1002/ame2.70107","DOIUrl":"https://doi.org/10.1002/ame2.70107","url":null,"abstract":"<p><strong>Background: </strong>The golden Syrian hamster is a valuable animal model for studying carcinogenesis, metabolic disorders, cardiovascular diseases, and viral infections due to its biological and pathological similarities to humans. However, the development of genetically engineered hamsters has lagged behind that of mice and rats, largely because of an embryonic development block at the two-cell stage in vitro. Although CRISPR/Cas9-mediated gene knockout has been achieved in hamsters, precise DNA fragment insertion or conditional knockout (cKO) models have not previously been reported, likely due to technical limitations in embryo manipulation and insufficient efficiency of homology-directed repair (HDR).</p><p><strong>Methods: </strong>In this study, we generated conditional alleles of the ApoF gene in golden Syrian hamsters. A two-cut strategy was applied using Cas9 protein, two sgRNAs, and a single donor plasmid containing exon 2 flanked by loxP sites and two ~0.8 kb homology arms. A mixture of Cas9 protein, sgRNAs, and the donor plasmid was microinjected into the pronuclei of one-cell stage hamster embryos.</p><p><strong>Results: </strong>The efficiency of CRISPR/Cas9-mediated loxP knock-in reached up to 27%, and the genetically modified floxed alleles were successfully transmitted through the germline. The functionality of the inserted loxP sites was validated by in vivo Cre-mediated recombination following local administration of AAV vectors, including AAV-cTnT-Cre in the heart and AAV-CMV-Cre in the brain.</p><p><strong>Conclusions: </strong>To our knowledge, this work represents the first successful establishment of a conditional knockout model in the golden Syrian hamster, providing a valuable tool for mechanistic studies of gene function and disease modeling.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145514752","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}