Animal models and experimental medicine最新文献

{"title":"Animal models of lung cancer: Phenotypic comparison of different animal models of lung cancer and their application in the study of mechanisms.","authors":"Zixuan Yang, Xianbin Zhao, Lili Tan, Pingxinyi Que, Tong Zhao, Wei Huang, Dejiao Yao, Songqi Tang","doi":"10.1002/ame2.70028","DOIUrl":"https://doi.org/10.1002/ame2.70028","url":null,"abstract":"<p><p>Lung cancer has one of the highest rates of incidence and mortality worldwide, making research on its mechanisms and treatments crucial. Animal models are essential in lung cancer research as they accurately replicate the biological characteristics and treatment outcomes seen in human diseases. Currently, various lung cancer models have been established, including chemical induction models, orthotopic transplantation models, ectopic transplantation models, metastasis models, and gene editing mouse models. Additionally, lung cancer grafts can be categorized into two types: tissue-based and cell-based grafts. This paper summarizes the phenotypes, advantages, and disadvantages of various induction methods based on their modeling techniques. The goal is to enhance the simulation of clinical lung cancer characteristics and to establish a solid foundation for future clinical research.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144096243","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":"Rapid severe hypertension and organ damage in two-kidney two-clip rats produced by different sizes of clips.","authors":"Jia-Sheng Tian, Qi-Sheng Ling, Yu-Chen Wei, Dao-Xin Wang, Chao-Yu Miao","doi":"10.1002/ame2.70027","DOIUrl":"https://doi.org/10.1002/ame2.70027","url":null,"abstract":"<p><strong>Background: </strong>The two-kidney two-clip (2K2C) rat model is widely used in hypertension, stroke, and drug studies. However, knowledge of this model is quite limited.</p><p><strong>Methods: </strong>In this study, U-shaped silver clips with inner diameters of 0.3, 0.25, and 0.2 mm were used to narrow bilateral renal arteries, inducing different extents of blood flow reduction for preparing 2K2C rats. Blood pressure (BP) was continuously measured during 2K2C procedures until 10 h after 2K2C, and long-term assessments of BP, organ damage, and serum biochemistry were performed at 1, 2, 4, and 6 weeks.</p><p><strong>Results: </strong>BP increased immediately when the 2K2C rats regained consciousness from anesthesia, with a 100% incidence of hypertension on the day of operation, and increased to a plateau at 2 weeks for 0.2 mm clips (248 mmHg), 4 weeks for 0.25 mm clips (219 mmHg), and perhaps 6 weeks for 0.3 mm clips (206 mmHg). BP levels displayed a negative correlation with clip sizes. Organ damage, including aortic and cardiac hypertrophy, cerebrovascular and cardiovascular injury, and renal atrophy or compensatory enlargement, occurred as early as 1 or 2 weeks after 2K2C. Routine serum biochemistry indicated organ dysfunction primarily at 4-6 weeks in 0.2 mm clips, whereas aspartate aminotransferase appeared a sensitive biomarker for early organ damage.</p><p><strong>Conclusion: </strong>2K2C can produce severe hypertension and multi-organ damage in a short time. 2K2C rats in 0.2 mm clips can be used as a hypertensive emergency model. This study provides crucial insights for guiding the development of targeted interventions.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144060364","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":"Influence of the arterial elastic component on the response to balloon angioplasty in femoral arteries of a healthy porcine model.","authors":"María Gracia de Garnica García, Marina Gil Bernabé, Claudia Pérez-Martínez, Laura Mola Solà, Luis Duocastella Codina, María Molina Crisol, Alex Gómez Castel, Armando Pérez de Prado","doi":"10.1002/ame2.70024","DOIUrl":"https://doi.org/10.1002/ame2.70024","url":null,"abstract":"<p><strong>Background: </strong>The efficacy of balloon angioplasty for treating peripheral artery disease is influenced by various factors, some of them not yet totally understood. This study aimed to evaluate the role of elastin content in vascular responses 28 days post-angioplasty using uncoated and paclitaxel-coated balloons with the same platform in femoral arteries of a healthy porcine model.</p><p><strong>Methods: </strong>Eight animals underwent balloon angioplasty on the external and internal branches of femoral arteries. Histopathologic evaluation was conducted at follow-up to assess the elastin content, vascular damage, morphological features, and neointimal formation.</p><p><strong>Results: </strong>The elastin content was significantly higher in the external than in the internal femoral artery (p = 0.0014). After balloon angioplasty, it was inversely correlated with vascular injury score (ρ = -0.4510, p = 0.0096), neointimal inflammation (ρ = -0.3352, p = 0.0607), transmural (ρ = -0.4474, p = 0.0103) and circumferential (ρ = -0.4591, p = 0.0082) smooth muscle cell loss, presence of proteoglycans (ρ = -0.5172, p = 0.0024), fibrin deposition (ρ = -0.3496, p = 0.0499), and adventitial fibrosis (ρ = -0.6229, p = 0.0002). Neointimal formation inhibition with paclitaxel was evident only in arteries with disruption of the internal elastic lamina, with a significant smaller neointimal area in arteries treated with paclitaxel-coated balloons compared to uncoated balloons (median [Q1-Q3]: 10.25 [7.49-15.64] vs. 24.44 [18.96-30.52], p = 0.0434).</p><p><strong>Conclusions: </strong>Elastin content varies between branches of the femoral artery and significantly influences the integrity of the internal elastic lamina, the vessel's adaptive response, and paclitaxel efficacy after balloon angioplasty.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144037422","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":"Neutrophil-to-lymphocyte and monocyte-to-lymphocyte ratios as inflammatory markers in the assessment of glycemic status in diabetic patients of Asir region.","authors":"Ayed A Dera, Abeer Abdullah Alghamdi, Mesfer Al-Shahrani, Reem M Al-Gahtani, Bashayer Saad Alghamdi, Gaffar Sarwar Zaman, Mohammed Abdul Rasheed, Hassan Al-Shehri, Lana Al-Qhtani, Syed Parween Ali, Umme Hani, Talha Bin Emran","doi":"10.1002/ame2.70023","DOIUrl":"https://doi.org/10.1002/ame2.70023","url":null,"abstract":"<p><strong>Background: </strong>Diabetes mellitus (DM) is a prevalent chronic metabolic condition characterized by high blood sugar levels, resulting from insufficient insulin production or ineffective insulin use, posing substantial global health issues. Research on the relationship between glycemic status and the ratio of neutrophils to lymphocytes (NLR) and monocytes to lymphocytes (MLR) is limited. This study aimed to fill these knowledge gaps by examining the connection between DM and inflammatory markers within the Asir region.</p><p><strong>Methods: </strong>Data from 3545 participants were retrospectively analyzed. The dataset, gathered between 2021 and 2023, comprises 38 laboratory tests obtained from the Future Lab Pioneer database. The study's inclusion criteria focused on diabetes profile tests (glycated hemoglobin [HbA1c] and fasting blood glucose [FBG]) and manually computed inflammatory markers (NLR and MLR), which were stratified by age and sex.</p><p><strong>Results: </strong>This study demonstrated significant differences in NLR levels compared with FBG levels across all adult age groups and adult female participants (p < 0.0001), as well as among all elderly age groups (p = 0.0006) and elderly women (p = 0.01). MLR levels were significant in all adult age groups (p = 0.04) and in adult women (p = 0.02). When NLR and MLR were compared to HbA1c levels, a significant difference in the mean NLR was found in adult women (p = 0.005). Additionally, the mean MLR levels were significant in all adult age groups (p = 0.04) and adult women (p = 0.02).</p><p><strong>Conclusion: </strong>Although a larger sample size is necessary for this research, the results indicate that NLR and MLR could serve as valuable indicators for evaluating inflammation in people with disrupted glucose metabolism, particularly in adult and female populations.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144045937","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":"Biocompatibility and healing patterns in experimentally induced canine tibial fractures using Pedicle screw-Rod external fixation.","authors":"Mohammad Mahdi Gooran, Ramin Mazaheri-Khameneh, Seyed Mohammad Hashemi-Asl, Rahim Hobbenaghi","doi":"10.1002/ame2.70022","DOIUrl":"https://doi.org/10.1002/ame2.70022","url":null,"abstract":"<p><strong>Background: </strong>Biological osteosynthesis preserves blood supply and promotes rapid healing by aligning fracture fragments without direct surgical exposure. Pedicle screws are primarily designed for internal fixation in spinal procedures. A key objective of many orthopedic studies is to assess the biocompatibility of implants with bone and adjacent soft tissue. This study aims to evaluate the biocompatibility and effects of the Pedicle screw-Rod configuration as a novel external fixation method in canine tibial osteotomy.</p><p><strong>Methods: </strong>With ethics approval, eight healthy, intact male dogs, aged 10-12 months and weighing between 20 and 22 kg, underwent a minimally invasive medial tibial approach for surgical fixation of tibial osteotomy using a Pedicle screw-Rod configuration. Postoperative evaluations included ultrasound assessments at the osteotomy site and histological evaluations at the bone-screw interface.</p><p><strong>Results: </strong>B-mode ultrasound evaluation indicated healing progress at all osteotomy sites. The color Doppler examination revealed an initial increase in signals in the surrounding soft tissue during the first 4 weeks post-operation, followed by a decrease in signals within the adjacent soft tissue between the 5th and 8th weeks. During this latter period, the signals were primarily concentrated on the bone surface and the callus. The bone-screw interface at various screw sites exhibited similar histological changes, indicating effective integration of the newly formed woven bone into the screw threads.</p><p><strong>Conclusions: </strong>Fixation of non-articular tibial osteotomy with Pedicle screw-Rod configuration resulted in secondary bone healing, characterized by abundant callus formation and neovascularization. This implant demonstrated favorable biocompatibility with bone and surrounding soft tissue, without significant complications.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144045884","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 effects of metformin, citral, Cymbopogon citratus extract and silver nanoparticles of Cymbopogon citratus extract on oxidative stress indices and Nrf2 levels in experimental type 2 diabetes in rats.","authors":"Milad Faraji, Mohammad Foad Noorbakhsh, Nasrin Kazemipour, Saeed Nazifi, Hamid Reza Moradi, Nasrollah Ahmadi, Maryam Azadmanesh","doi":"10.1002/ame2.70017","DOIUrl":"https://doi.org/10.1002/ame2.70017","url":null,"abstract":"<p><strong>Background: </strong>Diabetes, a metabolic disease marked by endocrine dysfunctions, significantly impacts oxidative stress pathways. This study explores the protective effects of lemongrass extract (LE), citral, and lemongrass extract-synthesized silver nanoparticles (LE-AgNP) against hyperglycemia-induced oxidative stress by modulating the Nrf2 pathway, which is crucial for antioxidant responses.</p><p><strong>Methods: </strong>Various techniques characterized the nanoparticles, including ultraviolet-visible spectroscopy, dynamic light scattering, zeta potential analysis, Fourier-transform infrared spectroscopy, scanning electron microscopy and transmission electron microscopy. Seventy rats, divided into seven groups, were used for in vivo experiments. Type 2 diabetes was induced using streptozotocin (65 mg/kg) and nicotinamide (90 mg/kg). After six weeks, biochemical parameters such as total antioxidant capacity, malondialdehyde, Nrf2, and Nrf2 miRNA were evaluated in pancreas tissue and blood serum, along with serum blood glucose levels.</p><p><strong>Results: </strong>LE-AgNP significantly improved weight gain, reduced food and water intake, and lowered blood glucose levels in diabetic rats. LE and citral did not significantly alter these parameters but prevented the decline in Nrf2 gene expression. LE-AgNP showed a significant increase in Nrf2 gene expression compared to the diabetic control group.</p><p><strong>Conclusions: </strong>This study highlights the potential of LE, citral, and especially LE-AgNP in mitigating oxidative stress induced by diabetes. LE-AgNP demonstrated superior therapeutic benefits, including improved oxidative stress conditions and hypoglycemic effects.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144051895","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":"Dual-energy X-ray absorptiometry for detecting neurogenic pulmonary edema in a mouse model of subarachnoid hemorrhage","authors":"Tatsushi Mutoh,&nbsp;Hiroaki Aono,&nbsp;Yushi Mutoh,&nbsp;Tatsuya Ishikawa","doi":"10.1002/ame2.70019","DOIUrl":"10.1002/ame2.70019","url":null,"abstract":"<p>Murine subarachnoid hemorrhage (SAH) induced using the filament perforation method is a useful in vivo experimental model to investigate the pathophysiological mechanisms in the brain underlying SAH. However, identifying mice with comorbid acute neurogenic pulmonary edema (NPE), a life-threatening systemic consequence often induced by SAH, in this model is difficult without histopathological investigations. Herein, we present an imaging procedure involving dual-energy X-ray absorptiometry (DXA) to identify NPE in a murine model of SAH. We quantified the lung lean mass (LM) and compared the relationship between micro-computed tomography (CT) evidence of Hounsfield unit (HU) values and histopathological findings of PE. Of the 85 mice with successful induction of SAH by filament perforation, 16 (19%) had NPE, as verified by postmortem histology. The DXA-LM values correlate well with CT-HU levels (<i>r</i> = 0.63, <i>p</i> &lt; 0.0001). Regarding the relationship between LM and HU in mice with post-SAH NPE, the LM was positively associated with HU values (<i>r</i>² = 0.43; <i>p</i> = 0.0056). A receiver operating characteristics curve of LM revealed a sensitivity of 87% and specificity of 57% for detecting PE, with a similar area under the curve as the HU (0.79 ± 0.06 vs. 0.84 ± 0.07; <i>p</i> = 0.21). These data suggest that confirming acute NPE using DXA-LM is a valuable method for selecting a clinically relevant murine NPE model that could be used in future experimental SAH studies.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"8 6","pages":"1146-1151"},"PeriodicalIF":0.0,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ame2.70019","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144060721","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":"Comparative analysis of short-term and long-term LL-37-induced rosacea-like mouse models: Histopathological features and inflammatory immune responses.","authors":"Yiling Wu, Chuanxi Zhang, Hui Jin, Ruiping Zheng, Tian Li, Fuyu Jin, Yaqian Li, Xuemin Gao, Hong Xu, Zhongqiu Wei, Jie Yang","doi":"10.1002/ame2.70020","DOIUrl":"https://doi.org/10.1002/ame2.70020","url":null,"abstract":"<p><strong>Background: </strong>It is well recognized that developing new animal models, refining the existing mouse models, and thoroughly characterizing their features are essential for gaining a deeper understanding of rosacea pathogenesis and for advancing therapeutic strategies in this direction. Accordingly, we aimed to characterize the pathological features of a long-term LL-37-induced mouse model of rosacea and to compare the disease manifestations and pathophysiological characteristics between short-term and long-term LL-37-induced models. A key focus was to investigate differential gene expression and the underlying mechanisms of immune system dysregulation in these models.</p><p><strong>Methods: </strong>We comparatively assessed skin lesion manifestations, the extent of inflammatory infiltration, sebaceous gland alterations, fibrosis, and angiogenesis in both models. Assessments were performed using photographic documentation, hematoxylin-eosin (HE) staining, Van Gieson's (VG) staining, immunohistochemistry, and Western blotting. Furthermore, we employed RNA sequencing to analyze differential gene expression in mouse skin. The RNA sequencing data were validated using immunofluorescence staining and Western blotting, with a specific focus on gene variations and mechanisms related to immune system dysregulation.</p><p><strong>Results: </strong>Mice subjected to long-term LL-37 induction developed rosacea-like pathological features, including angiogenesis, thickened skin tissue, and sebaceous gland hypertrophy. In the short-term LL-37-induced model, immune dysregulation primarily involved the innate immune response. However, long-term LL-37 induction resulted in significant activation of both innate and adaptive immune responses.</p><p><strong>Conclusion: </strong>The long-term LL-37-induced mouse model offers a valuable animal model for the detailed investigation of the pathological mechanisms driving moderate-to-severe rosacea with prolonged disease duration. Importantly, this model provides a significant experimental foundation for exploring the potential role of immune system dysregulation in rosacea pathogenesis.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144051893","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":"Comparative pathogenicity of vaccinia virus and mpox virus infections in CAST/EiJ mice: Exploring splenomegaly and transcriptomic profiles.","authors":"Yongzhi Hou, Jianrong Ma, Baoying Huang, Na Li, Lin Zhu, Ziqing Jia, Jiasen Yang, Jingjing Zhang, Wenjie Tan, Jing Xue","doi":"10.1002/ame2.70026","DOIUrl":"https://doi.org/10.1002/ame2.70026","url":null,"abstract":"<p><strong>Background: </strong>Vaccinia virus (VACV) and mpox virus (MPXV) belong to the orthopoxvirus genus and share high genetic similarity, making VACV widely used in the mpox pandemic. CAST/EiJ mice have been widely used for studying orthopoxvirus infection. However, the histopathological features of CAST/EiJ mice with mpox virus (MPXV) and vaccinia virus (VACV) infections have not been fully elucidated.</p><p><strong>Methods: </strong>Four group of CAST/EiJ mice were challenged with low-dose VACV (10³ PFU, VACV-L), high-dose VACV (10⁶ PFU, VACV-H), MPXV (10⁶ PFU) or PBS via intraperitoneal route, and the disease signs and body weight were monitored daily. Subsequently, viral loads and titers in the blood and spleen of CAST/EiJ mice were analyzed via qPCR and TCID₅₀ assay. Finally, the spleen samples were analyzed for histopathological, immunohistochemical and RNA-seq.</p><p><strong>Results: </strong>Herein, we found that VACV-L and MPXV caused splenomegaly via the intraperitoneal route, whereas VACV-H caused rapid lethality with limited splenomegaly. Transcriptome analysis from spleen revealed significant differences in gene expression between VACV-L and VACV-H groups, but the differentially expressed genes induced by splenomegaly between VACV-L and MPXV groups were highly similar. Furthermore, pathway enrichment analysis demonstrated that the VACV-L, VACV-H, and MPXV groups were all associated with the calcium, MAPK, and PI3K-Akt signaling pathway. Compared to the lethal infection observed in VACV-H group, the splenomegaly in the VACV-L and MPXV groups was characterized by extramedullary hematopoiesis and increased macrophages infiltration in the red pulp. Transcriptome analysis of the spleen demonstrated that the Wnt, tumor necrosis factor (TNF), and transforming growth factor β (TGF-β) signaling pathways may promote splenomegaly by modulating granulocyte infiltration and inflammatory responses. Compared to VACV-L group, the limited splenomegaly but lethality in VACV-H-infected mice might be associated with extensive splenic necrosis, diffuse congestion, and hemorrhage in the red pulp, as well as changes in the cGMP-PKG, Ras signaling, and Fc gamma R-mediated phagocytosis pathways.</p><p><strong>Conclusions: </strong>Our findings systematically compared the pathogenicity of VACV and MPXV in CAST/EiJ mice, incorporating splenic transcriptome analysis to provide insights into the potential molecular mechanism behind orthopoxvirus-induced splenomegaly in CAST/EiJ mice.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144044535","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":"Green-to-red spectral labeling: A novel polysynaptic retrograde tracing strategy in the marker footprint mouse model.","authors":"Yige Song, Jinyu Zeng, Yunyun Han, Aodi He, Houze Zhu","doi":"10.1002/ame2.70025","DOIUrl":"https://doi.org/10.1002/ame2.70025","url":null,"abstract":"<p><strong>Background: </strong>Rabies virus (RABV)-derived neuronal tracing tools are extensively applied in retrograde tracing due to their strict retrograde transsynaptic transfer property and low neurotoxicity. However, the RABV infection and expression of fluorescence products would be gradually cleared while the infected neurons still survive, a phenomenon known as non-cytolytic immune clearance (NCLIC). This phenomenon introduced the risk of fluorescence loss and led to the omission of a subset of neurons that should be labeled, thereby interfering in the analysis of tracing results.</p><p><strong>Methods: </strong>To compensate for the fluorescence loss problem, in this study, we developed a novel marker footprints (MF) mouse, involving a Cre recombinase-dependent red fluorescent reporter system and systemic expression of glycoprotein (G) and ASLV-A receptor (TVA). Using this mouse model combined with the well-developed RABV-EnvA-ΔG-GFP-Cre viral tool, we developed a novel green-to-red spectral labeling strategy.</p><p><strong>Results: </strong>Neurons in the MF mouse could be co-labeled with green fluorescence from the very quick expression of the viral tool and with red fluorescence from the relatively slow expression of the neuron itself, so neurons undergoing NCLIC with green fluorescence loss could be relabeled red. Furthermore, newly infected neurons could be labeled green and other neurons could be labeled yellow due to the temporal expression difference between the two fluorescent proteins.</p><p><strong>Conclusions: </strong>This is the first polysynaptic retrograde tracing labeling strategy that could label neurons using spectral fluorescence colors with only one injection of the viral tool, enabling its application in recognizing the labeling sequence of neurons in brain regions and enhancing the spatiotemporal resolution of neuronal tracing.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144044538","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}