{"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, Megumi Sasatani, Takashi Yamamoto, Osamu Kaminuma","doi":"10.1538/expanim.25-0036","DOIUrl":"10.1538/expanim.25-0036","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"457-462"},"PeriodicalIF":1.2,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12665987/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Soyasaponin I alleviates inflammation and oxidative stress in chronic obstructive pulmonary disease through inhibiting the mitogen-activated protein kinase (MAPK) signaling pathway.","authors":"Ruoqi Zhang, Jiabo Yuan, Congyao Wang, Ruiqi Zhao, Fengli Gao, Zhuying Li","doi":"10.1538/expanim.25-0007","DOIUrl":"10.1538/expanim.25-0007","url":null,"abstract":"<p><p>Chronic obstructive pulmonary disease (COPD) is a prevalent lung disease that mainly induced by cigarette smoking (CS). Soyasaponin I is an amphiphilic oleanane triterpenoid glycoside extracted form Astragali Radix. In order to investigate treatment strategies of COPD, this study focused on the effect of soyasaponin I on the lung tissue of COPD model. The mouse model of COPD was induced by CS exposure for 12 weeks, and was administrated with different doses of soyasaponin I. Subsequently, the morphology and histopathology of lung tissue, the proportion of inflammatory cell, the levels of inflammatory cytokines, and indicators of oxidative stress were assessed and analyzed. The signaling pathway potentially regulated by soyasaponin I in the pathogenesis of COPD were predicted by network pharmacology analysis and validated by western blot. Our results demonstrated that soyasaponin I mitigated the lung injury and bronchial lesions induced by COPD through reducing the lung coefficient, wall area of the bronchioles and Periodic Acid Schiff (PAS)-positive cells in the lung tissue. The CS-induced inflammation and oxidative stress was alleviated by soyasaponin I through reversing the levels of inflammatory cytokines and oxidative stress indicators. In addition, the phosphorylation of p38, JNK and ERK1/2 was activated in COPD model, and was reverted by soyasaponin I in the lung tissue. Collectively, the present study confirmed that soyasaponin I is an effective compound that attenuates the lung injury through inhibiting inflammatory response and oxidative stress via the mitogen-activated protein kinase (MAPK) signaling pathway.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"407-418"},"PeriodicalIF":1.2,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12665993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143994469","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 : 2025-10-08Epub Date: 2025-01-17DOI: 10.1538/expanim.24-0125
Xiangyu Fu, Xiang Ren, Maoyuan Zhao, Lan Li, Yaojia Zhou, Yanrong Lu, Chengshi Wang
{"title":"Disruption of intestinal barrier and dysbiosis of gut microbiota in an experimental rhesus macaque model with 6-year diabetes mellitus.","authors":"Xiangyu Fu, Xiang Ren, Maoyuan Zhao, Lan Li, Yaojia Zhou, Yanrong Lu, Chengshi Wang","doi":"10.1538/expanim.24-0125","DOIUrl":"10.1538/expanim.24-0125","url":null,"abstract":"<p><p>This study aims to clarify the disruption of gut barrier and dysbiosis of the microbiota in an experimental macaque model with 6-year diabetes mellitus (DM), and provide evidence for the application of therapeutic strategies targeting the human microbiota in the future. A single intravenous injection of high-dose streptozotocin was used to induce the type 1 diabetes (T1D) macaque model. Hematoxylin-Eosin (HE) and Periodic Acid Schiff (PAS) staining were conducted to observe colon morphological changes. The composition of gut microbiota was detected using 16S rRNA gene sequencing, and bioinformatics analysis was adopted to predict alterations in the microbial phenotype and function. Obvious intestinal inflammation and decreased goblet cells were observed in T1D macaques. 16S rRNA gene sequencing suggested a significantly different β diversity of the microbiota in the T1D group, where expanded Proteobacteria (dominantly Escherichia-Shigella) and Actinomycetota (formerly known as Actinobacteria) replaced the dominance of Bacillota (formerly known as Firmicutes) and Bacteroidota (formerly known as Bacteroidetes), indicating an imbalance in the microbial composition. Archaea was identified as a biomarker between groups. Moreover, with the reduction of beneficial bacteria (Lactobacillaceae) and the increase of pro-inflammatory bacteria and opportunistic pathogens (Enterobacteriaceae), the phenotypes of the microbiota were reversed, resulting in abnormal up- (e.g., carbohydrate and amino acid metabolism) or down-regulation (e.g., protein digestion and absorption) of multiple metabolic pathways. There were intestinal structural disorders and gut microbiota dysbiosis in T1D macaques, indicating that strategies targeting gut microbiota may be effective to treat metabolic diseases like DM.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"384-398"},"PeriodicalIF":1.2,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12665990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002798","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 : 2025-10-08Epub Date: 2025-06-07DOI: 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":"10.1538/expanim.25-0006","url":null,"abstract":"<p><p>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 microtubule-associated protein 1 light chain 3 beta (LC3) II and increased autophagy receptor 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.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"463-475"},"PeriodicalIF":1.2,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12665994/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Experimental AnimalsPub Date : 2025-10-08Epub Date: 2025-05-14DOI: 10.1538/expanim.24-0159
Himeka Hayashi, Hirotaka Sakamoto
{"title":"Sexual activity is predicted by digit ratio in rats.","authors":"Himeka Hayashi, Hirotaka Sakamoto","doi":"10.1538/expanim.24-0159","DOIUrl":"10.1538/expanim.24-0159","url":null,"abstract":"<p><p>The ratio of the second and fourth digits (2D:4D) is a morphological marker reflecting fetal exposure to sex steroid hormones. This ratio exhibits sexual dimorphism, with males typically showing a significantly lower ratio than females, which results from higher androgen exposure during the fetal period. While studies in humans have suggested a relationship between sexual orientation and the 2D:4D ratio, this relationship in rodents remains elusive. Here, we investigated this relationship using rats as an experimental model. We found that male rats exhibited significantly shorter 2D length than females, resulting in a lower 2D:4D ratio in males, similar to humans. Observations of sexual behavior revealed that males that ejaculated during the first mating test exhibited shorter 2D length compared to males those that did not ejaculate. When males were classified into two groups based on 2D length (long-2D and short-2D groups), short-2D males were more sexually active than long-2D males. Additionally, only short-2D males showed a preference for female odors. These findings suggest that, in rats, 2D length is a useful morphological marker reflecting sexual activity and preference. Furthermore, they provide evidence supporting the potential use of the 2D:4D ratio as a tool for studying the relationship between sexual orientation and the 2D:4D ratio in humans.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"452-456"},"PeriodicalIF":1.2,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12665992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076631","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}