Experimental Animals最新文献_第2页

Trophectoderm-specific gene manipulation using adeno-associated viral vectors. 利用腺相关病毒载体进行滋养外胚层特异性基因操作。

IF 2.2 4区农林科学

Experimental Animals Pub Date : 2025-07-11 Epub Date: 2025-01-11 DOI: 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":"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.","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}

引用次数: 0

Intestinal epithelial cell-specific restoration of Nrf2 gene in whole-body-knockout mice ameliorates acute colitis. 肠道上皮细胞特异性修复Nrf2基因在全身敲除小鼠改善急性结肠炎。

IF 2.2 4区农林科学

Experimental Animals Pub Date : 2025-07-11 Epub Date: 2025-01-25 DOI: 10.1538/expanim.24-0152

Tatsuhiro Sato, Keii To, Fumika Sakurai, Kanako Chihara, Eiji Warabi, Tomonori Isobe, Hideo Suzuki, Junichi Shoda, Kosuke Okada

{"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":"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.","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}

引用次数: 0

The usefulness of HbA1c measurement in diabetic mouse models using various devices. 使用各种设备测量糖尿病小鼠模型HbA1c的有效性。

IF 2.2 4区农林科学

Experimental Animals Pub Date : 2025-07-11 Epub Date: 2025-01-28 DOI: 10.1538/expanim.24-0154

Koya Miyazaki, Aisha Yokoi, Hiroyuki Inoue, Hirotaka Suzuki, Nozomi Kido, Ayumi Kanno, Maki Kimura-Koyanagi, Yoshiaki Kido, Shun-Ichiro Asahara

{"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":"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.","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}

引用次数: 0

Transferrin receptor knockdown attenuates atrial fibrillation by inhibiting cardiomyocyte ferroptosis and atrial fibrosis. TFRC敲低通过抑制心肌细胞铁下垂和心房纤维化来减轻心房颤动。

IF 2.2 4区农林科学

Experimental Animals Pub Date : 2025-07-11 Epub Date: 2025-02-26 DOI: 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":"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.","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}

引用次数: 0

Reference intervals for hematologic and biochemical values in Cynomolgus monkeys from different breeding populations in China. 中国不同繁殖种群食蟹猴血液学和生化指标的参考区间。

IF 2.2 4区农林科学

Experimental Animals Pub Date : 2025-07-11 Epub Date: 2025-06-24 DOI: 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":"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.","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}

引用次数: 0

A novel early onset spinocerebellar ataxia 13 BAC mouse model with cerebellar atrophy, tremor, and ataxic gait. 一种具有小脑萎缩、震颤和共济失调步态的新型早发性脊髓小脑共济失调13 BAC小鼠模型。

IF 2.2 4区农林科学

Experimental Animals Pub Date : 2025-07-11 Epub Date: 2025-03-20 DOI: 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":"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.","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}

引用次数: 0

Birth of offspring derived from cryopreserved rat sperm after shipment in a Styrofoam box at -80°C. 在-80°C的聚苯乙烯泡沫盒中运输后，由冷冻保存的大鼠精子衍生的后代出生。

IF 2.2 4区农林科学

Experimental Animals Pub Date : 2025-06-26 DOI: 10.1538/expanim.25-0041

Naomi Nakagata, Satohiro Nakao, Nobuyuki Mikoda, Katsuma Yamaga, Hiroshi Suzuki, Toru Takeo

{"title":"Birth of offspring derived from cryopreserved rat sperm after shipment in a Styrofoam box at -80°C.","authors":"Naomi Nakagata, Satohiro Nakao, Nobuyuki Mikoda, Katsuma Yamaga, Hiroshi Suzuki, Toru Takeo","doi":"10.1538/expanim.25-0041","DOIUrl":"https://doi.org/10.1538/expanim.25-0041","url":null,"abstract":"Archiving and sharing cryopreserved rat sperm can improve animal experiments' reliability, reproducibility, and sustainability in the scientific community. When sharing cryopreserved sperm from genetically engineered rats, a shipment system is required. Generally, a dry shipper, which can maintain at below -150°C, is the most widely used for sperm transport. However, using it for shipping cryopreserved sperm faces some difficulties, such as the risk of transporting hazardous materials (liquid nitrogen), its high cost, and the round-trip fee. Recently, the shipment of cryopreserved mouse sperm with dry ice at -79°C has been alternatively accepted in the scientific community. However, its outcome in terms of the fertilization and developmental abilities of the cryopreserved rat sperm was not examined. Therefore, this study aimed to examine the fertilization and developmental abilities of cryopreserved rat sperm after being stored in a deep freezer (-80°C) and dry ice (-79°C). We also demonstrated the transport of cryopreserved rat sperm in a Styrofoam box with dry ice. The fertilization rate of cryopreserved sperm stored in a deep freezer or dry ice was comparable to that in liquid nitrogen. In the transport experiment, the rat sperm transported between Kumamoto and Hokkaido maintained a high fertilization rate, and live pups were obtained from the embryos derived from the transported sperm. Fertilization and developmental abilities of cryopreserved rat sperm were maintained after shipment using a Styrofoam box with dry ice for storage.","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505200","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}

引用次数: 0

The protective effects of retinoic acid-induced protein 14 on ischemia/reperfusion-induced myocardial apoptosis involves over-autophagy repression. 维甲酸诱导的蛋白14对缺血/再灌注诱导的心肌凋亡的保护作用包括抑制过度自噬。

IF 2.2 4区农林科学

Experimental Animals Pub Date : 2025-06-07 DOI: 10.1538/expanim.25-0006

Junjie Xu, Lei Zhang, Peng Zhang, Yanhong Su, Yuxia Gao

{"title":"The protective effects of retinoic acid-induced protein 14 on ischemia/reperfusion-induced myocardial apoptosis involves over-autophagy repression.","authors":"Junjie Xu, Lei Zhang, Peng Zhang, Yanhong Su, Yuxia Gao","doi":"10.1538/expanim.25-0006","DOIUrl":"https://doi.org/10.1538/expanim.25-0006","url":null,"abstract":"Uncontrolled activation of autophagy following ischemia/reperfusion (I/R) injury leads to cell death. The superfamily of ankyrin repeat proteins (N-Ank protein) was reported to be involved in autophagy regulation and cardiac protection. Bioinformatics analysis was performed (GSE61592 and GSE160516) and ten N-Ank proteins were differentially expressed in I/R models. Retinoic acid-induced protein 14 (RAI14), a member of N-Ank protein family, was upregulated in I/R-injured cardiac tissue and was first selected for research. A mouse I/R model was established by ligating the left anterior descending coronary artery to induce 90 min of ischemia, followed by 72 h of reperfusion. RAI14 was found upregulated in ischemic penumbra. RAI14 overexpression in cardiac tissue by injecting adeno-associated virus-9-RAI14 plasmid system via tail vein improved cardiac function and reduced infarct and apoptosis. Furthermore, the activated autophagy in ischemic penumbra of I/R mice was reversed by RAI14 overexpression along with decreased LC3-II and increased p62 expressions. RAI14 silence showed an opposite effect. A cell model was established by using mouse cardiomyocytes HL-1 underwent hypoxia/reoxygenation (H/R) treatment. Similarly, H/R also enhanced RAI14 expression and RAI14 overexpression inhibited H/R-induced apoptosis and autophagy in HL-1 cells. Mechanistically, autophagy inhibitor, the AKT/mTOR pathway, was found to be suppressed in mouse and cell models whereas RAI14 overexpression activated this pathway. Collectively, we demonstrated that compensatory increase of RAI14 inhibited I/R-induced myocardial injury by preventing excessive autophagy through activating the AKT/mTOR pathway, which providing an idea to explore strategies for preventing I/R injury.","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247101","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}

引用次数: 0

Evaluation of a mixture of medetomidine, alfaxalone and butorphanol as an alternative drug for euthanasia in mice. 美托咪定、阿法沙龙和布托啡诺合剂作为小鼠安乐死替代药物的评价。

IF 2.2 4区农林科学

Experimental Animals Pub Date : 2025-06-07 DOI: 10.1538/expanim.25-0052

Megumi Kiyoto, Kenta Nakano, Yukiyoshi Watai, Yukiko Shimizu, Mayu Uchihashi, Tadashi Okamura

{"title":"Evaluation of a mixture of medetomidine, alfaxalone and butorphanol as an alternative drug for euthanasia in mice.","authors":"Megumi Kiyoto, Kenta Nakano, Yukiyoshi Watai, Yukiko Shimizu, Mayu Uchihashi, Tadashi Okamura","doi":"10.1538/expanim.25-0052","DOIUrl":"https://doi.org/10.1538/expanim.25-0052","url":null,"abstract":"Euthanasia agents should induce a rapid and painless loss of consciousness, followed by cardiopulmonary arrest and subsequent brain death. Injectable drugs such as pentobarbital sodium are commonly used for laboratory rodents due to their quick and smooth action. However, the discontinuation of pharmaceutical-grade pentobarbital sodium and secobarbital sodium in Japan, along with a global shortage of pentobarbital in late 2020, has increased the demand for new injectable euthanasia drugs. In Japan, the combination of medetomidine, midazolam, and butorphanol (MMB), as well as a newer formulation in which midazolam is replaced with alfaxalone (MAB), have been widely used as balanced anesthesia for rodents. To evaluate their potential as alternative euthanasia agents in mice, we compared mortality rates and the time intervals to the loss of the righting reflex, respiratory arrest, and cardiac arrest following anesthetic administration. An intraperitoneal injection of MAB at five times the anesthetic dose induced death within 10 min with the loss of the righting reflex, respiratory arrest, and cardiac arrest occurring at 1.5 min, 4 min, and 9 min respectively, in all mice, which was comparable to those observed with 300 mg/kg of secobarbital. In contrast, none of the mice administered MMB at five times the anesthetic dose experienced cardiopulmonary arrest within 30 min. Intraperitoneal overdose of MAB induces rapid and irreversible death, supporting its potential use as an effective euthanasia agent in mice.","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247100","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}

引用次数: 0

Effect of gamma-ray exposure on the genome-editing efficiency of improved genome-editing via oviductal nucleic acids delivery (i-GONAD). 伽马射线暴露对经输卵管核酸传递（i-GONAD）改良基因组编辑效率的影响。

IF 2.2 4区农林科学

Experimental Animals Pub Date : 2025-05-27 DOI: 10.1538/expanim.25-0036

Anarkhuu Bold-Erdene, Kento Miura, Norimasa Yamasaki, Shuka Miura, Sawako Ogata, Osamu Kaminuma

{"title":"Effect of gamma-ray exposure on the genome-editing efficiency of improved genome-editing via oviductal nucleic acids delivery (i-GONAD).","authors":"Anarkhuu Bold-Erdene, Kento Miura, Norimasa Yamasaki, Shuka Miura, Sawako Ogata, Osamu Kaminuma","doi":"10.1538/expanim.25-0036","DOIUrl":"https://doi.org/10.1538/expanim.25-0036","url":null,"abstract":"DNA double-strand breaks (DSBs) are among the most hazardous cellular damages, potentially leading to cell death or oncogenesis if unrepaired. Genome editing methods, such as the CRISPR/Cas9 system, induce DSBs and utilize these repair pathways for gene knockout and knock-in. Although ionizing radiation also induces DSBs, it is not clear whether the efficiency of genome editing is affected by ionizing radiation. This study investigated the impact of gamma-ray exposure on the genome editing efficiency of the improved genome editing via oviductal nucleic acid delivery (i-GONAD) method. Gamma-rays were exposed to pregnant mice receiving i-GONAD targeting the Hr gene, whose mutation causes hair loss in mice. The exposure on the fertilization day (Day 0) decreased natural delivery rates and litter sizes, with notable effects at 0.3 Gy or higher. Although the proportions of hairless offspring obtained by i-GONAD differed greatly between single-guide RNAs (sgRNAs) used, total mutation rates, including hairless, mosaic, and indel, were equivalent. Gamma-ray exposure on Day 0 and the day after fertilization (Day 1) similarly and almost dose-dependently enhanced the genome editing efficiency evaluated by the total mutation rate. This study suggests the improvement of genome editing efficiency by gamma-ray exposure, at least in i-GONAD method, potentially facilitating the creation of diverse experimental animal models.","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172812","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}

引用次数: 0