Tra Thi Huong Dinh, Chigusa Imura, Mayu Shiokawa, Shinya Ayabe, Atsushi Yoshiki, Haruhisa Inoue, Takanori Amano
{"title":"A partial deletion of the Tardbp 3´UTR affects TDP-43 regulation and leads to motor dysfunction in mice.","authors":"Tra Thi Huong Dinh, Chigusa Imura, Mayu Shiokawa, Shinya Ayabe, Atsushi Yoshiki, Haruhisa Inoue, Takanori Amano","doi":"10.1538/expanim.25-0061","DOIUrl":"https://doi.org/10.1538/expanim.25-0061","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that causes the selective loss of motor neurons. A histopathological hallmark of ALS is the cytoplasmic aggregation of TDP-43, a ubiquitously expressed RNA-binding protein involved in transcription and splicing regulation. To prevent abnormal accumulation, TDP-43 controls its expression levels through an autoregulatory feedback loop. While most ALS studies have focused on pathogenic variants that impair the protein function of TDP-43, the mechanisms underlying endogenous TDP-43 dysregulation mediated by non-coding elements, including the 3´ untranslated region (3´UTR), remain incompletely understood. In this study, we generated a mouse model carrying a targeted deletion of the Tardbp 3´UTR that encompasses the TDP-binding region, polyadenylation signals, and alternative intronic sequences. Our findings demonstrate that the Tardbp 3´UTR is essential for normal mouse development. Loss of this region led to decreased Tardbp mRNA expression and embryonic lethality after gastrulation. Young heterozygous mice were phenotypically normal with no overt disruption in TDP-43 autoregulation. However, aged heterozygous mice displayed mild locomotor dysfunction accompanied by a modest increase in spinal cord TDP-43 protein levels and a reduction in motor neuron numbers. These findings indicate that regulatory elements within the Tardbp 3´UTR play a pivotal role in normal development and contribute to TDP-43 pathology relevant to ALS.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Suppression of USP2 in mouse skeletal muscle: a model of oxidative stress in muscle tissue.","authors":"Masaki Fujimoto, Tomohito Iwasaki, Marina Hosotani Saito, Naoki Takahashi, Mayuko Hashimoto, Eiki Takahashi, Hiroshi Kitamura","doi":"10.1538/expanim.25-0032","DOIUrl":"https://doi.org/10.1538/expanim.25-0032","url":null,"abstract":"<p><p>Emerging evidence indicates that oxidative stress in skeletal muscle is a prerequisite for sarcopenia in diabetic patients. In this study, we show that ubiquitin-specific protease (USP) 2 mitigates the accumulation of reactive oxygen species (ROS) in mature muscle cells. Treatment with ML364, a canonical USP2 inhibitor, robustly increased mitochondrial ROS in mouse C2C12 myotubes and caused an accompanying increase in the glutathione disulfide (GSSG)/glutathione (GSH) ratio. ML364 also caused mitochondrial damage in C2C12 myotubes, resulting in a reduction in intracellular adenosine triphosphate levels. Correspondingly, under diabetic condition, the muscle-specific Usp2-knockout (msUsp2KO) C57BL/6N mice exhibited a significantly higher lipid peroxide level and GSSG/GSH ratio in skeletal muscle than the control mice. The msUsp2KO mice also exhibited augmented insulin resistance and glucose intolerance, but showed no obvious deterioration in muscle weight or histology relative to the control mice. However, damaged mitochondria in the soleus muscle were more frequently observed in msUsp2KO mice than in the control mice. Together, these data suggest that USP2 mitigates ROS accumulation and subsequent mitochondrial damage in muscle cells in mice.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sherilyn M T Choo, Fatin H Mohamad, Syarifah Maisarah Sayed Mohamad, Jafri Malin Abdullah, Khairul Bariyyah Abd Halim, Azzmer Azzar Abdul Hamid, Ahmad Tarmizi Che Has
{"title":"Exploring the role of zolpidem in alleviating cognitive and motor impairments in chronic cerebral hypoperfusion: a rat model study with in vivo and in silico insights.","authors":"Sherilyn M T Choo, Fatin H Mohamad, Syarifah Maisarah Sayed Mohamad, Jafri Malin Abdullah, Khairul Bariyyah Abd Halim, Azzmer Azzar Abdul Hamid, Ahmad Tarmizi Che Has","doi":"10.1538/expanim.25-0038","DOIUrl":"https://doi.org/10.1538/expanim.25-0038","url":null,"abstract":"<p><p>The ε-containing GABA (A) receptors (GABAARs), a lesser-studied subtype within the GABAAR family, have garnered attention due to their distinct pharmacological properties and potential involvement in brain injury. Zolpidem (ZPM), a widely used Z-drug, is known to induce paradoxical effects in patients with brain injury, although the underlying molecular mechanisms remain unclear. In this study, a chronic cerebral hypoperfusion (CCH) rat model was established using Permanent Bilateral Occlusion of the Common Carotid Arteries (PBOCCA), followed by administration of ZPM at doses of 1.0, 2.0, and 4.0 mg/kg. Behavioral assessments demonstrated that the 1.0 mg/kg dose of ZPM significantly improved spatial learning and memory acquisition (P<0.01) and enhanced memory retention (P<0.001), whereas higher doses resulted in sedation and cognitive impairment. Immunohistochemical analysis revealed an upregulation of the ε subunit expression in the hippocampal CA1 and CA3 regions of CCH rats (P<0.05), suggesting alterations in receptor composition in response to cerebral hypoperfusion. Further investigation of ZPM's interaction with ε-containing GABAARs (specifically the α1β2ε subtype) was conducted using in silico techniques. Molecular docking identified the α1+/ε- binding interface as a favorable ZPM binding site, with key residues being either conserved or suitably replaced. Molecular dynamics simulations demonstrated that ZPM stabilizes the receptor while permitting conformational flexibility, consistent with its role as a positive allosteric modulator. These findings provide evidence that ZPM interacts with ε-containing GABAARs, potentially explaining its paradoxical effects observed in brain injury models.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Diverse Cre recombinase expression pattern in Albumin-Cre driver rats.","authors":"Saeko Ishida, Keiko Taguchi, Ryuya Iida, Kosuke Hattori, Hiroaki Taketsuru, Kazuto Yoshimi, Masayuki Yamamoto, Tomoji Mashimo","doi":"10.1538/expanim.24-0174","DOIUrl":"10.1538/expanim.24-0174","url":null,"abstract":"<p><p>Rats (Rattus norvegicus) have been widely utilized as model animals due to their physiological characteristics, making them suitable for surgical and long-term studies. They have played a crucial role in biomedical research, complementing studies conducted in mice. The advent of genome editing technologies has facilitated the generation of genetically modified rat strains, advancing studies in experimental animals. Among these innovations, Cre-driver rat models have emerged as powerful tools for spatiotemporal control of gene expression. However, their development and characterization remain less advanced compared to mouse models. In this study, we developed liver-targeting Cre knock-in rats and reporter knock-in rats to evaluate Cre recombinase expression profiles in different genetic contexts. Our results revealed that insertion orientation and promoter origin significantly influence Cre expression patterns. Notably, forward insertion of the Albumin (Alb) promoter-driven Cre sequence at the ROSA26 locus resulted in ubiquitous Cre expression, while reverse insertion confined Cre expression predominantly to the liver. Interestingly, Cre expression under an endogenous Alb promoter unexpectedly induced expression in non-liver tissues, which may suggest a potential link to the in vivo dynamics of albumin. These findings underscore the importance of rigorous characterization in Cre-based transgenic systems. By elucidating the roles of promoter origin, insertion site, and orientation, our study provides valuable insights for optimizing Cre-driver rat models. These findings pave the way for refining genetic strategies to enhance tissue specificity and reliability in functional genomics and disease modeling.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"328-334"},"PeriodicalIF":2.2,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12270594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Experimental AnimalsPub Date : 2025-07-11Epub Date: 2025-01-11DOI: 10.1538/expanim.24-0165
Tatsuya Nakagawa, Chihiro Emori, Masahito Ikawa
{"title":"Trophectoderm-specific gene manipulation using adeno-associated viral vectors.","authors":"Tatsuya Nakagawa, Chihiro Emori, Masahito Ikawa","doi":"10.1538/expanim.24-0165","DOIUrl":"10.1538/expanim.24-0165","url":null,"abstract":"<p><p>In mammals, blastocyst-stage trophectoderm (TE) contacts the maternal body at the time of implantation and forms the placenta after implantation, which supports the development of the fetus. Studying gene function in TE and placenta is important to understand normal implantation and pregnancy processes and their dysfunction. However, genetically modified mice are commonly generated by manipulating pronuclear-stage zygotes, which modify both the genome of the fetus and the placenta. Therefore, we previously developed TE/placenta-specific gene expression technology by transducing blastocysts with lentiviral vectors. However, the zona pellucida (ZP) needed to be removed before transduction. In this study, we examined various adeno-associated viral (AAV) vectors to develop a new TE/placenta-specific gene transduction method. As AAV1 can path through ZP, we succeeded in trophoblast-specific gene expression without ZP removal. Furthermore, TE cells genetically modified by AAV1-Cre contributed uniformly to the placenta. Our new technology contributes to advances in implantation and placenta research and leads to the development of new assisted reproductive technology.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"310-318"},"PeriodicalIF":2.2,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12270592/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142978096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Intestinal epithelial cell-specific restoration of Nrf2 gene in whole-body-knockout mice ameliorates acute colitis.","authors":"Tatsuhiro Sato, Keii To, Fumika Sakurai, Kanako Chihara, Eiji Warabi, Tomonori Isobe, Hideo Suzuki, Junichi Shoda, Kosuke Okada","doi":"10.1538/expanim.24-0152","DOIUrl":"10.1538/expanim.24-0152","url":null,"abstract":"<p><p>Unbalanced redox homeostasis leads to the production of reactive oxygen species and exacerbates inflammatory bowel disease. To investigate the role of the transcription factor Nrf2, a major antioxidative stress sensor, in intestinal epithelial cells (IECs), we generated IEC-specific Nrf2 gene knock-in mice (Nrf2-vRes), which express Nrf2 only in IECs, using the cre/loxp system. Colitis was induced in wild-type (WT) mice, whole-body Nrf2-knockout (Nrf2-KO) mice, and Nrf2-vRes mice by administering dextran sulfate sodium (DSS) for 1 week (acute model) or intermittently for 5 weeks (chronic model). The mRNA and protein levels of NAD(P)H:quinone oxidoreductase 1 (NQO1), which is involved in the oxidative stress response in a manner regulated by Nrf2, were reduced in Nrf2-KO compared with those in WT, while these decreases were reversed in Nrf2-vRes at all timepoints. Nrf2-KO mice administered DSS developed more severe colitis with higher disease activity index, higher leucine-rich α2 glycoprotein in serum, shorter colon length, and more severe epithelial damage and infiltration of inflammatory cells histopathologically than did WT mice in the acute model; moreover, these exacerbations of colitis were ameliorated in Nrf2-vRes mice. However, these differences were not observed among the three sets of mice in the chronic model. IEC-specific expression of Nrf2 ameliorated DSS-induced acute colitis. These results suggest that Nrf2 expression in IECs plays a protective role against early-stage colitis and undertakes important regulatory functions during intestinal inflammation.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"335-347"},"PeriodicalIF":2.2,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12270596/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The usefulness of HbA1c measurement in diabetic mouse models using various devices.","authors":"Koya Miyazaki, Aisha Yokoi, Hiroyuki Inoue, Hirotaka Suzuki, Nozomi Kido, Ayumi Kanno, Maki Kimura-Koyanagi, Yoshiaki Kido, Shun-Ichiro Asahara","doi":"10.1538/expanim.24-0154","DOIUrl":"10.1538/expanim.24-0154","url":null,"abstract":"<p><p>In most cases, the diagnosis of diabetes in animal models is based solely on blood glucose levels. While hemoglobin A1c (HbA1c) is widely used in the diagnosis of diabetes in humans, it is rarely measured in mice in diabetes research. This is thought to be because there are no established reference values for mouse HbA1c, as well as the fact that there are very few reports on the variability and reproducibility of measurements taken using different devices. In this study, we measured HbA1c levels in diabetic mouse models using different devices based on different principles, including capillary electrophoresis, high-performance liquid chromatography, and enzymatic methods, and compared the results. A positive correlation was observed between blood glucose and HbA1c levels in all measurement methods, and high reproducibility was confirmed in the measurement of HbA1c. However, HbA1c levels measured using the enzymatic method were slightly higher than those measured using the other two methods. In addition, an examination of diabetic mice given a sodium-glucose cotransporter 2 inhibitor, which is used to treat diabetes, revealed that there was a 2-week difference in the fluctuation of mouse HbA1c levels compared with the fluctuation of blood glucose levels. Based on these results, it is thought that HbA1c can be a reliable indicator in diabetic mouse models, and it is expected to make the evaluation of abnormal glucose metabolism in mice more reliable.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"319-327"},"PeriodicalIF":2.2,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12270598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Experimental AnimalsPub Date : 2025-07-11Epub Date: 2025-02-26DOI: 10.1538/expanim.24-0127
Yufei Zhan, Yang Zhou, Chi Zhang, Zongwang Zhai, Yi Yang, Xingpeng Liu
{"title":"Transferrin receptor knockdown attenuates atrial fibrillation by inhibiting cardiomyocyte ferroptosis and atrial fibrosis.","authors":"Yufei Zhan, Yang Zhou, Chi Zhang, Zongwang Zhai, Yi Yang, Xingpeng Liu","doi":"10.1538/expanim.24-0127","DOIUrl":"10.1538/expanim.24-0127","url":null,"abstract":"<p><p>Atrial fibrillation (AF) is a common arrhythmia in clinical. Its most important pathophysiological factor is atrial fibrosis. Transferrin receptor (TFRC) promotes ferroptosis by facilitating iron uptake. Its role in AF is unknown. TFRC expression in Angiotensin II (Ang II)-induced AF mice was significantly upregulated. TFRC knockdown significantly reduced AF occurrence. TFRC silence ameliorated myocardial fibrosis by inhibiting transforming growth factor-β1 (TGF-β1)/Smad2 pathway in vivo. TFRC interference reduced ferroptosis by inhibiting lipid oxidation product generation in vivo. Ang II-induced HL-1 cardiomyocyte model was employed to simulate an in vivo situation. The in vitro results were consistent with the in vivo results. Forkhead box O3 (FOXO3) was reported to protect atrium against fibrosis and participate in ferroptosis. FOXO3 exerted transcriptional repressive activity by binding to TFRC promoter. FOXO3 overexpression protected HL-1 cells against ferroptosis, which was reversed by TFRC overexpression. In summary, TFRC knockdown reduces AF occurrence by ameliorating atrial fibrosis through inhibiting cardiomyocyte ferroptosis under FOXO3 regulation.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"348-361"},"PeriodicalIF":2.2,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12270597/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Experimental AnimalsPub Date : 2025-07-11Epub Date: 2025-06-24DOI: 10.1538/expanim.24-0110
Shuyan Wang, Yongtao Liu, Caiyun Li, Lei Shi, Qi Zhao, Jiang Lv, Yuwen Zhang, Xijie Wang, Yan Chang
{"title":"Reference intervals for hematologic and biochemical values in Cynomolgus monkeys from different breeding populations in China.","authors":"Shuyan Wang, Yongtao Liu, Caiyun Li, Lei Shi, Qi Zhao, Jiang Lv, Yuwen Zhang, Xijie Wang, Yan Chang","doi":"10.1538/expanim.24-0110","DOIUrl":"10.1538/expanim.24-0110","url":null,"abstract":"<p><p>The Cynomolgus monkey is the most widely used models in non-clinical studies. As factors like age, gender, and breeding province may affect hematologic and serum biochemical parameters, it is important to establish base values of these parameters by these three factors and to determine the effects of these factors on the parameters. In total, 1794 Cynomolgus monkeys (Male: 901, Female: 893) were selected. A total of 24 hematologic and 21 serum biochemical parameters were measured, and the effects of age, gender, and breeding province were analyzed. Base values for hematologic and serum biochemical parameters were established by age, gender, and breeding province. A significant neutrophil percent, alkaline phosphatase, and creatinine differences were observed between different ages; a significant alkaline phosphatase, gamma glutamyl transpeptidase, and creatinine differences were observed between males and females; a significant lymphocyte percent, neutrophil percent, reticulocyte count, alkaline phosphatase, gamma glutamyl transpeptidase, and creatinine differences were observed between different breeding provinces. The results emphasize the importance of improving base values by age, gender, and breeding provinces. There was no statistically significant difference in most of the above parameters, and Cynomolgus monkeys from different breeding provinces can be used in the same study.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"375-383"},"PeriodicalIF":2.2,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12270593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Experimental AnimalsPub Date : 2025-07-11Epub Date: 2025-03-20DOI: 10.1538/expanim.24-0118
Junxiang Yin, Jerelyn A Nick, Swati Khare, Heidi E Kloefkorn, Ming Gao, Michael Wu, Jennifer White, James L Resnick, Kyle D Allen, Harry S Nick, Michael F Waters
{"title":"A novel early onset spinocerebellar ataxia 13 BAC mouse model with cerebellar atrophy, tremor, and ataxic gait.","authors":"Junxiang Yin, Jerelyn A Nick, Swati Khare, Heidi E Kloefkorn, Ming Gao, Michael Wu, Jennifer White, James L Resnick, Kyle D Allen, Harry S Nick, Michael F Waters","doi":"10.1538/expanim.24-0118","DOIUrl":"10.1538/expanim.24-0118","url":null,"abstract":"<p><p>Spinocerebellar ataxia 13 (SCA13) is an autosomal dominant neurological disorder caused by mutations in KCNC3. Our previous studies revealed that KCNC3 (Potassium Voltage-Gated Channel Subfamily C Member 3) mutation R423H results in an early-onset form of SCA13. Previous biological models of SCA13 include zebrafish and Drosophila but no mammalian systems. More recently, mouse models with Kcnc3 mutations presented behavioral abnormalities but without obvious pathological changes in the cerebellum, a hallmark of patients with SCA13. Here, we present a novel transgenic mouse model by bacterial artificial chromosome (BAC) recombineering to express the full-length mouse Kcnc3 expressing the R424H mutation. This BAC-R424H mice exhibited behavioral and pathological changes mimicking the clinical phenotype of the disease. The BAC-R424H mice (homologous to R423H in human) developed early onset clinical symptoms with aberrant gait, tremor, and cerebellar atrophy. Histopathological analysis of the cerebellum in BAC-R424H mice showed progressive Purkinje cell loss and thinning of the molecular cell layer. Additionally, Purkinje cells of BAC-R424H mice showed significantly lower spontaneous firing frequency with a corresponding increase in inter-spike interval compared to that of wild-type mice. Our SCA13 transgenic mice recapitulate both neuropathological and behavioral changes manifested in human SCA13 R423H patients and provide an advantageous approach to understanding the role of voltage-gated potassium channel in cerebellar morphogenesis and function. This mammalian in vivo model will lead to further understanding of the R423H allelic form of SCA13 from the molecular to the behavioral level and serve as a platform for testing potential therapeutic compounds.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"362-374"},"PeriodicalIF":2.2,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12270595/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}