{"title":"Acyl-CoA thioesterase 1 (ACOT1) overexpression alleviates heart failure by inhibiting oxidative stress and cardiomyocyte apoptosis through the Kelch-like ECH-associated protein1-NF-E2-related factor2 (KEAP1-NRF2) pathway.","authors":"Xiaolu Hou, Guoling Hu, Heling Wang, Ying Yang, Qi Sun, Xiuping Bai","doi":"10.1538/expanim.24-0129","DOIUrl":"10.1538/expanim.24-0129","url":null,"abstract":"<p><p>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. Adeno-associated virus serotype 9 (AAV9)-mediated ACOT1 overexpression improved cardiac function and pathological injury of heart tissues in transverse aortic coarctation (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 reactive oxygen species (ROS) and malondialdehyde (MDA) levels and elevated superoxide dismutase (SOD) and glutathione (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 Kelch-like ECH-associated protein1-NF-E2-related factor2 (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.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"10-22"},"PeriodicalIF":1.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12861710/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Generation of mice expressing liver-specific fluorescent genes and the optimal conditions for signal detection via in vivo imaging.","authors":"Shuho Hori, Hideki Hayashi, Kayoko Iwao, Ayaka Nakamura, Hideaki Sumiyoshi, Yutaka Inagaki, Masato Ohtsuka, Hiromi Miura","doi":"10.1538/expanim.25-0092","DOIUrl":"10.1538/expanim.25-0092","url":null,"abstract":"<p><p>In vivo imaging enables real-time detection of excitation and emission signals and is useful for the noninvasive evaluation of temporal changes in biological tissues. The near-infrared fluorescent protein iRFP can be used for deep-tissue imaging because it emits light at wavelengths that are less attenuated by biological tissues. However, autofluorescence originating from diet, tissues, and the imaging environment can interfere with fluorescence detection; therefore, appropriate animal pretreatment and optimization of imaging conditions are essential. We generated two mouse strains: Alb<sup>eGiR</sup> reporter mice, in which enhanced green fluorescent protein (eGFP) and iRFP713 genes were tandemly inserted downstream of the Albumin gene, and hairless mice (Hr<sup>Δ164/Δ164</sup>), carrying a mutation in the hairless gene. Their offspring were used in in vivo imaging experiments to investigate: (i) the localization of eGFP and iRFP713 fluorescence, (ii) the influence of hair on fluorescence detection, and (iii) suitable filter combinations for fluorescence detection. In the resulting mice, liver-specific expression of both eGFP and iRFP713 was observed at the same anatomical location. Although autofluorescence was more prominent in hairless mice than in furred mice, signal detection was improved either by using longer-wavelength excitation/emission filters or by applying spectral unmixing to separate the target signal. These findings provide practical guidance for optimizing in vivo fluorescence imaging conditions using standard IVIS platforms.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"99-109"},"PeriodicalIF":1.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12826568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137030","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 : 2026-01-01Epub Date: 2025-07-19DOI: 10.1538/expanim.25-0061
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":"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":"40-49"},"PeriodicalIF":1.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12826566/pdf/","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":"OA","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":"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":"50-62"},"PeriodicalIF":1.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12826574/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"D-galactose treatment accumulates AGEs but induces no further detrimental effects in HR-1 mouse skin.","authors":"Mako Isemura, Ryoga Kinosita, Sakura Hattori, Karina Kouzaki, Yuki Tamura, Hiroya Urabe, Hiroyuki Uno, Ryuji Akimoto, Koichi Nakazato","doi":"10.1538/expanim.25-0026","DOIUrl":"10.1538/expanim.25-0026","url":null,"abstract":"<p><p>As aging affects the appearance of the skin, anti-aging research has intensified in dermatology, skincare, and aesthetic medicine. Because natural aging takes a very long time, one essential anti-aging approach is to pharmacologically mimic aging, such as with D-galactose treatment. Hairless mice (HR-1) have been extensively used in skin research because of their lack of body hair and ease of animal care. In the present study, HR-1 mice were treated with D-galactose to determine whether detrimental effects were induced in the skin. After 3 months of D-galactose treatment, AGEs in the skin significantly increased. On the other hand, no signs of skin disorders (dermal thickness, type I collagen content, expression of various genes, collagen synthesis, and degradation signals) were observed. Even when the concentration of D-galactose increased, no apparent changes in dermal thickness were observed. These findings suggest that D-galactose treatment induces AGEs accumulation but no further detrimental effects in the HR-1 skin.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"81-89"},"PeriodicalIF":1.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12826573/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145014185","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}