Experimental Animals最新文献_第3页

Dominant effect of a single amino acid mutation in the motor domain of myosin VI on hearing in mice. 肌球蛋白VI运动结构域单个氨基酸突变对小鼠听力的显性影响。

IF 2.2 4区农林科学

Experimental Animals Pub Date : 2025-04-20 Epub Date: 2024-12-17 DOI: 10.1538/expanim.24-0141

Yuta Seki, Shumpei P Yasuda, Xuehan Hou, Kayoko Tahara, Ornjira Prakhongcheep, Ai Takahashi, Yuki Miyasaka, Hirohide Takebayashi, Yoshiaki Kikkawa

{"title":"Dominant effect of a single amino acid mutation in the motor domain of myosin VI on hearing in mice.","authors":"Yuta Seki, Shumpei P Yasuda, Xuehan Hou, Kayoko Tahara, Ornjira Prakhongcheep, Ai Takahashi, Yuki Miyasaka, Hirohide Takebayashi, Yoshiaki Kikkawa","doi":"10.1538/expanim.24-0141","DOIUrl":"10.1538/expanim.24-0141","url":null,"abstract":"An unconventional myosin, myosin VI gene (MYO6), contributes to recessive and dominant hearing loss in humans and mice. The Kumamoto shaker/waltzer (ksv) mouse is a model of deafness resulting from a splice-site mutation in Myo6. While ksv/ksv homozygous mice are deaf due to cochlear hair cell stereocilia fusion at the neonatal stage, the hearing phenotypes of ksv/+ heterozygous mice have been less clear. Due to this splicing error, most MYO6 protein expression is lost in ksv mice; however, MYO6 with a single amino acid mutation (p.E461K) remains expressed. In this study, we investigated the hearing phenotypes and effect of a p.E461K mutation in ksv/+ heterozygous mice. Hearing tests indicated that hearing loss in ksv/+ mice arises concurrently at both low and high frequencies. In the low-frequency region, stereocilia fusions were detected in the inner hair cells of ksv/+ mice. Expression analysis revealed abnormal MYO6 expression and localization, along with atypical expression of proteins in the basal region of the stereocilia, suggesting that these abnormalities may contribute to stereocilia fusion in ksv/+ mice. Conversely, although the expression patterns of MYO6 and stereociliary basal-region proteins appeared normal in the cochlear area corresponding to high-frequency sounds, stereocilia loss in the outer hair cells was observed in ksv/+ mice. These findings suggest that the ksv/+ mice exhibit distinct mechanisms underlying hearing loss across areas responsible for low- and high-frequency hearing, differing from those previously reported in heterozygous Myo6 mice with loss-of-function and missense mutant alleles.","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"251-263"},"PeriodicalIF":2.2,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12044356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853162","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

DNA repair protein RAD50 is involved in the streptozotocin-induced diabetes susceptibility of mice. DNA修复蛋白RAD50参与链脲佐菌素诱导的小鼠糖尿病易感性。

IF 2.2 4区农林科学

Experimental Animals Pub Date : 2025-04-20 Epub Date: 2024-12-24 DOI: 10.1538/expanim.24-0071

Yuki Miyasaka, Tomoki Maegawa, Takuma Nagura, Misato Kobayashi, Naru Babaya, Hiroshi Ikegami, Fumihiko Horio, Tamio Ohno

{"title":"DNA repair protein RAD50 is involved in the streptozotocin-induced diabetes susceptibility of mice.","authors":"Yuki Miyasaka, Tomoki Maegawa, Takuma Nagura, Misato Kobayashi, Naru Babaya, Hiroshi Ikegami, Fumihiko Horio, Tamio Ohno","doi":"10.1538/expanim.24-0071","DOIUrl":"10.1538/expanim.24-0071","url":null,"abstract":"Streptozotocin (STZ) is widely used as a pancreatic beta-cell toxin to induce experimental diabetes in rodents. Strain-dependent variations in STZ-induced diabetes susceptibility have been reported in mice. Differences in STZ-induced diabetes susceptibility are putatively related to pancreatic beta-cell fragility via DNA damage response. In this study, we identified two STZ-induced diabetes susceptibility regions in chromosome 11 (Chr11) of Nagoya-Shibata-Yasuda (NSY) mice via congenic mapping using the C3H-11NSY consomic strains, in which the entire Chr11 of STZ-resistant C3H/He (C3H) mice was replaced with that of NSY mice, and named them STZ susceptibility region for NSY (Ssnsy)-1 and -2, respectively. Screening for variants in the Ssnsy1 region revealed that NSY mice exhibited a characteristic missense c.599G>T (p.G200V) variant in a highly conserved region within the DNA repair gene, RAD50 double-strand break repair protein (Rad50). Subsequently, we generated R2B1-Rad50 knock-in mice, in which c.599T in Rad50 of STZ-susceptible C3H.NSY-R2B1 subcongenic mice was replaced with c.599G via genome editing. Compared with C3H.NSY-R2B1 mice, and R2B1-Rad50 knock-in mice showed suppressed hyperglycemia, incidence of diabetes, and decrease in plasma insulin levels following single high-dose and multiple low-dose injections of STZ. Our results suggest Rad50 as a susceptibility gene for STZ-induced diabetes that is involved in pancreatic beta-cell fragility. Forward genetic approaches using inbred mouse strains with STZ susceptibility as a phenotypic indicator will further elucidate the molecular mechanisms of pancreatic beta-cell destruction via DNA damage response.","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"264-275"},"PeriodicalIF":2.2,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12044362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893387","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

Acot1 overexpression alleviates heart failure by inhibiting oxidative stress and cardiomyocyte apoptosis through the Keap1-Nrf2 pathway. Acot1过表达通过Keap1-Nrf2途径抑制氧化应激和心肌细胞凋亡，从而缓解心力衰竭。

IF 2.2 4区农林科学

Experimental Animals Pub Date : 2025-04-16 DOI: 10.1538/expanim.24-0129

Xiaolu Hou, Guoling Hu, Heling Wang, Ying Yang, Qi Sun, Xiuping Bai

{"title":"Acot1 overexpression alleviates heart failure by inhibiting oxidative stress and cardiomyocyte apoptosis through the Keap1-Nrf2 pathway.","authors":"Xiaolu Hou, Guoling Hu, Heling Wang, Ying Yang, Qi Sun, Xiuping Bai","doi":"10.1538/expanim.24-0129","DOIUrl":"https://doi.org/10.1538/expanim.24-0129","url":null,"abstract":"Heart failure (HF) is a clinical syndrome related to multiple causes, including oxidative stress. Acyl-CoA thioesterase 1 (Acot1) is an enzyme in fatty acids metabolism, but it remains unclear in HF. Transverse aortic coarctation induced HF mouse model and hypoxia-stimulated cardiomyocyte (HL-1) model were established. Acot1 expression was down-regulated in heart tissues of HF mice. AAV9-mediated Acot1 overexpression improved cardiac function and pathological injury of heart tissues in TAC-induced HF mice. Acot1 overexpression ameliorated oxidative stress in heart tissues of HF mice and hypoxia-stimulated HL-1 cells, as indicated by reduced ROS and MDA levels and elevated SOD and GSH levels. We found that Acot1 overexpression inhibited apoptosis both in vivo and in vitro, with decreased protein levels of cleaved PARP, cleaved caspase-3, and cleaved caspase-9. Mechanically, Acot1 activated Keap1-Nrf2 pathway, leading to the nuclear translocation of Nrf2 and increased Nrf2-regulated gene NQO1 expression. Rescue experiment indicated that ML385 (Nrf2 inhibitor) abolished the effect of Acot1 overexpression on oxidative stress. Collectively, these results suggested that Acot1 overexpression protects heart from injury by inhibiting oxidative stress and apoptosis, possibly through activating Keap1-Nrf2 pathway.","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143995907","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

Dual-route medetomidine-alfaxalone-butorphanol anesthesia: a refined protocol for balanced anesthesia in male rabbits. 美托咪定-阿尔法沙龙-布托啡诺双路麻醉：一种完善的雄性家兔平衡麻醉方案。

IF 2.2 4区农林科学

Experimental Animals Pub Date : 2025-04-15 DOI: 10.1538/expanim.24-0151

Risa Iwanaga, Munekatsu Ita, Kanako Sumi, Chizuko Kodama, Mohammad Ibrahim Qasimi, Jun Tamura, Ko Nakanishi, Kayoko Matsumura, Masami Morimatsu, Yasuhiro Yoshida, Teppei Nakamura

{"title":"Dual-route medetomidine-alfaxalone-butorphanol anesthesia: a refined protocol for balanced anesthesia in male rabbits.","authors":"Risa Iwanaga, Munekatsu Ita, Kanako Sumi, Chizuko Kodama, Mohammad Ibrahim Qasimi, Jun Tamura, Ko Nakanishi, Kayoko Matsumura, Masami Morimatsu, Yasuhiro Yoshida, Teppei Nakamura","doi":"10.1538/expanim.24-0151","DOIUrl":"https://doi.org/10.1538/expanim.24-0151","url":null,"abstract":"Injectable anesthesia is widely used in laboratory animals because of its ease of administration and minimal equipment requirements. However, it necessitates careful monitoring as well as thermal and oxygen support. This study evaluated the efficacy of medetomidine-alfaxalone-butorphanol (MAB) anesthesia in male rabbits using a dual-route administration protocol. The anesthetic doses were as follows: medetomidine, 0.2 mg/kg; alfaxalone, 2.0 mg/kg; and butorphanol, 2.0 mg/kg. MAB anesthesia, administered via intravenous and subcutaneous routes, induced rapid and smooth induction, achieving anesthetic scores comparable to those of medetomidine-midazolam-butorphanol (MMB) anesthesia. MAB anesthesia resulted in mild hypothermia during the procedure. Upon atipamezole administration, rabbits under MAB anesthesia exhibited faster recovery of the righting reflex and respiration rate than those under MMB. Importantly, no abnormal behaviors, such as jumping or agitation, were observed during induction or recovery, as reported with alfaxalone use in other species. Both protocols maintained spontaneous breathing, although transient hypoxemia was observed in all rabbits. The dual-route MAB protocol provided effective anesthesia while addressing the limitations of conventional MMB anesthesia in rabbits, suggesting its potential as a refined anesthetic method for this species. Unlike mice, which showed weaker anesthetic effects with MAB compared to MMB, MAB demonstrated superior anesthetic properties in rabbits. This study highlights the importance of species-specific anesthetic protocols and the potential benefits of MAB anesthesia in rabbits, particularly its smooth induction and recovery profile, without adverse behaviors often associated with alfaxalone in other species.","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143974465","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

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 : 2025-04-04 DOI: 10.1538/expanim.24-0110

Shuyan Wang, Yongtao Liu, Caiyun Li, Lei Shi, Qiao 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, Qiao Zhao, Jiang Lv, Yuwen Zhang, Xijie Wang, Yan Chang","doi":"10.1538/expanim.24-0110","DOIUrl":"https://doi.org/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":""},"PeriodicalIF":2.2,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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 : 2025-03-20 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":"https://doi.org/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":""},"PeriodicalIF":2.2,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

TFRC 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 : 2025-02-26 DOI: 10.1538/expanim.24-0127

Yufei Zhan, Yang Zhou, Chi Zhang, Zongwang Zhai, Yi Yang, Xingpeng Liu

{"title":"TFRC 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":"https://doi.org/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 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. 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":""},"PeriodicalIF":2.2,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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 : 2025-01-28 DOI: 10.1538/expanim.24-0154

Kohya 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":"Kohya 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":"https://doi.org/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":""},"PeriodicalIF":2.2,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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 : 2025-01-25 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":"https://doi.org/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":""},"PeriodicalIF":2.2,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Diverse Cre recombinase expression pattern in Albumin-Cre driver rats. 白蛋白驱动大鼠不同Cre重组酶表达模式。

IF 2.2 4区农林科学

Experimental Animals Pub Date : 2025-01-22 DOI: 10.1538/expanim.24-0174

Saeko Ishida, Keiko Taguchi, Ryuya Iida, Kosuke Hattori, Hiroaki Taketsuru, Kazuto Yoshimi, Masayuki Yamamoto, Tomoji Mashimo

{"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":"https://doi.org/10.1538/expanim.24-0174","url":null,"abstract":"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.","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0