Experimental Animals最新文献_第8页

Circadian and sleep phenotypes in a mouse model of Alzheimer's disease characterized by intracellular accumulation of amyloid β oligomers. 以淀粉样β寡聚体细胞内积累为特征的阿尔茨海默病小鼠模型的昼夜节律和睡眠表型。

IF 2.4 4区农林科学

Experimental Animals Pub Date : 2024-05-03 Epub Date: 2023-12-14 DOI: 10.1538/expanim.23-0104

Tomoyuki Sato, Tomoyo Ochiishi, Sayaka Higo-Yamamoto, Katsutaka Oishi

{"title":"Circadian and sleep phenotypes in a mouse model of Alzheimer's disease characterized by intracellular accumulation of amyloid β oligomers.","authors":"Tomoyuki Sato, Tomoyo Ochiishi, Sayaka Higo-Yamamoto, Katsutaka Oishi","doi":"10.1538/expanim.23-0104","DOIUrl":"10.1538/expanim.23-0104","url":null,"abstract":"Disturbances in sleep-wake and circadian rhythms may reportedly precede the onset of cognitive symptoms in the early stages of Alzheimer's disease (AD); however, the underlying mechanisms of these AD-induced sleep disturbances remain unelucidated. To specifically evaluate the involvement of amyloid beta (Aβ) oligomers in AD-induced sleep disturbances, we examined circadian and sleep phenotypes using an Aβ-GFP transgenic (Aβ-GFP Tg) mouse characterized by intracellular accumulation of Aβ oligomers. The circadian rhythm and free-running period of wheel running activity were identical between Aβ-GFP Tg and littermate wild-type mice. The durations of rapid eye movement (REM) sleep were elongated in Aβ-GFP Tg mice; however, the durations of non-REM sleep and wakefulness were unaffected. The Aβ-GFP Tg mice exhibited shifts in the electroencephalogram (EEG) power spectra toward higher frequencies in the inactive light phase. These findings suggest that the intracellular accumulation of Aβ oligomers might be associated with sleep quality; however, its impact on circadian systems is limited.","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"186-192"},"PeriodicalIF":2.4,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11091359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138801034","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

Lonicerin alleviates ovalbumin-induced asthma of mice via inhibiting enhancer of zeste homolog 2/nuclear factor-kappa B signaling pathway. 忍冬素通过抑制EZH2/NF-κB信号通路减轻卵清蛋白诱导的小鼠哮喘。

IF 2.4 4区农林科学

Experimental Animals Pub Date : 2024-05-03 Epub Date: 2023-11-10 DOI: 10.1538/expanim.23-0068

Rui Dai, Yun Xiang, Rui Fang, Hai-Han Zheng, Qing-Song Zhao, Yan Wang

{"title":"Lonicerin alleviates ovalbumin-induced asthma of mice via inhibiting enhancer of zeste homolog 2/nuclear factor-kappa B signaling pathway.","authors":"Rui Dai, Yun Xiang, Rui Fang, Hai-Han Zheng, Qing-Song Zhao, Yan Wang","doi":"10.1538/expanim.23-0068","DOIUrl":"10.1538/expanim.23-0068","url":null,"abstract":"Asthma is the most common chronic disease in the respiratory system of children caused by abnormal immunity that responses to common antigens. Lonicerin exerts anti-inflammatory activity in other inflammatory models through targeting enhancer of zeste homolog 2 (EZH2) that is related to asthma. We sought to explore the role and mechanism of lonicerin in regulating allergic airway inflammation. Mice were intraperitoneally injected 10 µg ovalbumin (OVA) on postnatal day 5 (P5) and P10, and then inhaled 3% aerosolized OVA for 10 min every day on P18-20, to establish asthmatic mice model. Lonicerin (10 or 30 mg/kg) was given to mice by intragastric administration on P16-P20. Notably, the administration of lonicerin amended infiltration of inflammatory cells and mucus hypersecretion. OVA-specific IgE level, inflammatory cell count and inflammatory cytokines in asthmatic mice were reduced after lonicerin treatment. Moreover, it suppressed the activity of EZH2 and activation of nuclear factor-kappa B (NF-κB) as evidenced by decreasing tri-methylation of histone H3 at lysine 27 and reducing nuclear translocation of NF-κB p65. In a word, Lonicerin may attenuate asthma by inhibiting EZH2/NF-κB signaling pathway.","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"154-161"},"PeriodicalIF":2.4,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11091354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89717533","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

Functional role of IL-19 in a mouse model of L-arginine-induced pancreatitis and related lung injury. IL-19在l -精氨酸诱导的胰腺炎及相关肺损伤小鼠模型中的功能作用

IF 2.4 4区农林科学

Experimental Animals Pub Date : 2024-05-03 Epub Date: 2023-12-06 DOI: 10.1538/expanim.23-0094

Naoshige Ono, Joji Horikoshi, Takeshi Izawa, Kazuhiro Nishiyama, Miyuu Tanaka, Takashi Fujita, Mitsuru Kuwamura, Yasu-Taka Azuma

{"title":"Functional role of IL-19 in a mouse model of L-arginine-induced pancreatitis and related lung injury.","authors":"Naoshige Ono, Joji Horikoshi, Takeshi Izawa, Kazuhiro Nishiyama, Miyuu Tanaka, Takashi Fujita, Mitsuru Kuwamura, Yasu-Taka Azuma","doi":"10.1538/expanim.23-0094","DOIUrl":"10.1538/expanim.23-0094","url":null,"abstract":"IL-19 is a member of IL-10 family and is mainly produced by macrophages. Acute pancreatitis (AP) is an inflammatory disease characterized by acinar cell injury and necrosis. In the present study, the role of IL-19 in AP and AP-associated lung injury in mice was explored using L-arginine-induced pancreatitis. Experimental pancreatitis was induced by intraperitoneal injection of L-arginine in wild-type (WT) and IL-19 gene-deficient (IL-19 KO) mice. Among the mice treated with L-arginine, the serum amylase level was significantly increased in the IL-19 KO mice, and interstitial edema, analyzed using hematoxylin and eosin-stained sections, was aggravated mildly in IL-19 KO mice compared with WT mice. Furthermore, the mRNA expression of tumor necrosis factor-α was significantly upregulated in IL-19 KO mice treated with L-arginine compared with WT mice treated with L-arginine. IL-19 mRNA was equally expressed in the pancreases of both control and L-arginine-treated WT mice. The conditions of lung alveoli were then evaluated in WT and IL-19 KO mice treated with L-arginine. In mice with L-arginine-induced pancreatitis, the alveolar area was remarkedly decreased, and expression of lung myeloperoxidase was significantly increased in IL-19 KO mice compared with WT mice. In the lungs, the mRNA expression of IL-6 and inducible nitric oxide synthase was significantly increased in IL-19 KO mice compared with WT mice. In summary, IL-19 was proposed to alleviate L-arginine-induced pancreatitis by regulating TNF-α production and to protect against AP-related lung injury by inhibiting neutrophil migration.","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"175-185"},"PeriodicalIF":2.4,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11091360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138498137","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 compensatory increase of Gli-similar 3 inhibited neuronal apoptosis through regulating Mps one binder kinase activator 1b (MOB1b): a possible strategy for the functional recovery after spinal cord injury. Gli-similar 3的代偿性增加通过调节Mps one bind kinase activator 1b (MOB1b)抑制神经细胞凋亡：脊髓损伤后功能恢复的一种可能策略。

IF 2.4 4区农林科学

Experimental Animals Pub Date : 2024-02-14 Epub Date: 2023-08-12 DOI: 10.1538/expanim.23-0041

Hong-Bo Yang, Ying Li, Xiu-Hai Li, Qing-Ming Yan, Xian-Zhang Han, Jian Cao, Hong-Peng Sang, Jin-Long Li

{"title":"The compensatory increase of Gli-similar 3 inhibited neuronal apoptosis through regulating Mps one binder kinase activator 1b (MOB1b): a possible strategy for the functional recovery after spinal cord injury.","authors":"Hong-Bo Yang, Ying Li, Xiu-Hai Li, Qing-Ming Yan, Xian-Zhang Han, Jian Cao, Hong-Peng Sang, Jin-Long Li","doi":"10.1538/expanim.23-0041","DOIUrl":"10.1538/expanim.23-0041","url":null,"abstract":"Spinal cord injury (SCI) is a devastating disease characterized by neuronal apoptosis. Gli-similar 3 (GLIS3), a transcriptional factor, was involved in cell apoptosis and associated with the transcription of downstream target genes related to neuronal function. However, the function of GLIS3 in SCI remains unknown. Therefore, we used the mouse model of SCI to explore the role of GLIS3 in SCI. The results showed that GLIS3 expression was significantly increased in spinal cord tissues of SCI mice, and GLIS3 overexpression promoted the functional recovery, reserved histological changes, and inhibited neuronal apoptosis after SCI. Through online tools, the potential target genes of GLIS3 were analyzed and we found that Mps one binder kinase activator 1b (Mob1b) had a strong association with SCI among these genes. MOB1b is a core component of Hippo signaling pathway, which was reported to inhibit cell apoptosis. MOB1b expression was significantly increased in mice at 7 days post-SCI and GLIS3 overexpression further increased its expression. Dual-luciferase reporter assay revealed that GLIS3 bound to the promoter of Mob1b and promoted its transcription. In conclusion, our findings reveal that the compensatory increase of GLIS3 promotes functional recovery after SCI through inhibiting neuronal apoptosis by transcriptionally regulating MOB1b. Our study provides a novel target for functional recovery after SCI.","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"61-72"},"PeriodicalIF":2.4,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10877155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9992686","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

Effects of two weeks of food restriction on toxicological parameters in cynomolgus monkeys. 禁食两周对猴毒性参数的影响

IF 2.4 4区农林科学

Experimental Animals Pub Date : 2024-02-14 Epub Date: 2023-08-29 DOI: 10.1538/expanim.23-0017

Nozomi Fujisawa, Tomochika Matsushita, Saori Matsuo, Mayumi Hiranuma, Hiroko Azabu, Ryota Saito, Shun-Ichiro Komatsu, Atsuhiko Kato, Naoto Toyota, Junko Taketo, Hiromi Suzuki

{"title":"Effects of two weeks of food restriction on toxicological parameters in cynomolgus monkeys.","authors":"Nozomi Fujisawa, Tomochika Matsushita, Saori Matsuo, Mayumi Hiranuma, Hiroko Azabu, Ryota Saito, Shun-Ichiro Komatsu, Atsuhiko Kato, Naoto Toyota, Junko Taketo, Hiromi Suzuki","doi":"10.1538/expanim.23-0017","DOIUrl":"10.1538/expanim.23-0017","url":null,"abstract":"Animals frequently eat less after a test-article treatment in nonclinical toxicological studies, and it can be difficult to distinguish test article-derived toxicities from secondary changes related to this reduced food intake. Therefore, in this study, we restricted the food intake of cynomolgus monkeys (Cambodian, male, n=2 or 3, 48 ± 3 months old) to 25% of the control for two weeks and evaluated the effects on toxicological parameters (general conditions, body weight, electrocardiography, urinalysis, hematology, blood chemistry, bone marrow analysis, pathological examination). After 2 weeks, the monkeys exhibited decreases in bone marrow erythropoiesis (e.g., decreases in reticulocytes and bone marrow erythrocytes), as well as glycogenesis induction (e.g., increase in aspartate aminotransferase (AST)) and malnutrition (e.g., decrease in triglyceride and systemic adipocytes atrophy). Additionally, histopathological analysis revealed granuloma and inflammatory cell infiltration in coronary fat, which had never been found in previous food restriction studies using other animal species. These findings will enable researchers to more accurately evaluate the toxicological risks of test articles that simultaneously induce food intake reduction.","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"73-82"},"PeriodicalIF":2.4,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10877149/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10176958","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

Disruption of testis-enriched cytochrome c oxidase subunit COX6B2 but not COX8C leads to subfertility. 破坏睾丸富含的细胞色素 c 氧化酶亚基 COX6B2 而非 COX8C 会导致不育。

IF 2.2 4区农林科学

Experimental Animals Pub Date : 2024-02-14 Epub Date: 2023-07-10 DOI: 10.1538/expanim.23-0055

Keisuke Shimada, Yonggang Lu, Masahito Ikawa

{"title":"Disruption of testis-enriched cytochrome c oxidase subunit COX6B2 but not COX8C leads to subfertility.","authors":"Keisuke Shimada, Yonggang Lu, Masahito Ikawa","doi":"10.1538/expanim.23-0055","DOIUrl":"10.1538/expanim.23-0055","url":null,"abstract":"Mammalian sperm flagellum contains the midpiece characterized by a mitochondrial sheath that packs tightly around the axoneme and outer dense fibers. Mitochondria are known as the \"powerhouse\" of the cell, and produce ATP through the tricarboxylic acid (TCA) cycle and oxidative phosphorylation (OXPHOS). However, the contribution of the TCA cycle and OXPHOS to sperm motility and male fertility is less clear. Cytochrome c oxidase (COX) is an oligomeric complex localized within the mitochondrial inner membrane, and the terminal enzyme of the mitochondrial electron transport chain in eukaryotes. Both COX6B2 and COX8C are testis-enriched COX subunits whose functions in vivo are poorly studied. Here, we generated Cox6b2 and Cox8c knockout (KO) mice using the CRISPR/Cas9 system. We examined their fertility and sperm mitochondrial function to determine the significance of testis-enriched COX subunits in male fertility. The mating test revealed that disrupting COX6B2 induces male subfertility, while disrupting COX8C does not affect male fertility. Cox6b2 KO spermatozoa showed low sperm motility, but mitochondrial function was normal according to oxygen consumption rates. Therefore, low sperm motility seems to cause subfertility in Cox6b2 KO male mice. These results also indicate that testis-enriched COX, COX6B2 and COX8C, are not essential for OXPHOS in mouse spermatozoa.","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"1-10"},"PeriodicalIF":2.2,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10877148/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10101512","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

Time course of histopathology of bleomycin-induced pulmonary fibrosis using an intratracheal sprayer in mice. 使用气管内喷雾器诱导小鼠肺纤维化的博莱霉素组织病理学时间过程。

IF 2.4 4区农林科学

Experimental Animals Pub Date : 2024-02-14 Epub Date: 2023-07-28 DOI: 10.1538/expanim.23-0048

Hideyuki Kobayashi, Ayami Tachi, Sumihiko Hagita

{"title":"Time course of histopathology of bleomycin-induced pulmonary fibrosis using an intratracheal sprayer in mice.","authors":"Hideyuki Kobayashi, Ayami Tachi, Sumihiko Hagita","doi":"10.1538/expanim.23-0048","DOIUrl":"10.1538/expanim.23-0048","url":null,"abstract":"Idiopathic pulmonary fibrosis (IPF) is a poor prognosis disease that affects approximately 5 million people worldwide, and the detailed mechanisms underlying the pathogenesis of IPF remain unclear. Bleomycin-induced pulmonary fibrosis has been widely used as a representative animal model of IPF that induces fibrosis in lung tissue. The lungs of rodent consist of five lobes and each bronchus enters each lobe of the lung at a different bifurcation angle, path length, and diameter. The method of administration of bleomycin is considered as important thing to establish appropriate animal models. We conducted a time-dependent histopathological study to examine how pulmonary fibrosis develops in each lung lobe when bleomycin was intratracheally sprayed in ICR mice. And we then explored the suitable points for evaluation of anti-fibrotic agents in this model. As a result, we found that homogeneous fibrosis was induced in the 5 lobes of the lungs following initial inflammation. The expression of transforming growth factor (TGF)-β1 and phospho-Smad2 (pSmad2) was observed from Day 1, and their positivity increased until Day 21. In conclusion, we have observed a detailed time course of histological changes in bleomycin-induced pulmonary fibrosis in ICR mice using the aerosolization technique. We found that our protocol can induce a highly homogeneous lesion in the lung and that the most suitable time point to assess anti-fibrotic agents is 14 days after treatment in this model.","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"41-49"},"PeriodicalIF":2.4,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10877150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9951834","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

Comparison of retinal parameters between rhesus and cynomolgus macaques. 恒河猴与猕猴视网膜参数的比较。

IF 2.4 4区农林科学

Experimental Animals Pub Date : 2024-02-14 Epub Date: 2023-07-18 DOI: 10.1538/expanim.22-0022

Chengjie He, Jingyi Peng, Jiayi Jin, Wanwen Shao, Yongxin Zheng, Liuxueying Zhong

{"title":"Comparison of retinal parameters between rhesus and cynomolgus macaques.","authors":"Chengjie He, Jingyi Peng, Jiayi Jin, Wanwen Shao, Yongxin Zheng, Liuxueying Zhong","doi":"10.1538/expanim.22-0022","DOIUrl":"10.1538/expanim.22-0022","url":null,"abstract":"Nonhuman primates are important research models for basic vision research, preclinical pathogenesis, and treatment studies due to strong similarities in retinal structure and function with humans. We compared retinal parameters between 10 healthy normal rhesus macaques (Macaca mulatta) and 10 cynomolgus macaques (Macaca fascicularis) by optical coherence tomography and electroretinography. The Heidelberg Spectralis® HRA+OCT and Roland multifocal electrophysiometer were used to analyze retinal morphology, multifocal electroretinograms (mfERGs), and full-field electroretinograms (ff-ERGs). Mean retinal thickness was lowest in the central fovea of macaques and did not differ significantly between species, but the retinal thicknesses of the nerve fiber ganglion cell layer and the inner plexiform layer were significantly different. The amplitude density of the N1 wave was lower in rhesus macaques than in cynomolgus macaques in ring and quadrant areas. Dark-adapted 3.0 oscillatory potentials (reflection of amacrine cell activity) and light-adapted 30-hz flicker ERG (a sensitive cone-pathway-driven response) waveforms of the ff-ERG were similar in both species, while the times to peaks in dark-adapted 0.01 ERG (the rod-driven response of bipolar cells) and dark-adapted 3.0 ERG (combined rod and cone system responses) as well as the implicit times of the a- and b-waves in light-adapted 3.0 ERG (the single-flash cone response) were substantially different. This study provides normative retinal parameters for nonhuman primate research on basic and clinical ophthalmology, as well as a reference for researchers in the appropriate selection of rhesus or cynomolgus macaques as models for ophthalmology studies.","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"20-28"},"PeriodicalIF":2.4,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10877147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10185806","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

Renal transcriptome analysis of uninephrectomized db/db mice identified a mechanism for the transition to severe diabetic nephropathy. 对未切除肾脏的 db/db 小鼠的肾脏转录组分析确定了向严重糖尿病肾病转变的机制。

IF 2.4 4区农林科学

Experimental Animals Pub Date : 2024-02-14 Epub Date: 2023-07-21 DOI: 10.1538/expanim.22-0168

Mariko Maekawa, Tatsuya Maekawa, Tomohiko Sasase, Takeshi Wakashima, Atsuhiro Uemura, Kinuko Uno, Takeshi Ohta, Takahisa Yamada

{"title":"Renal transcriptome analysis of uninephrectomized db/db mice identified a mechanism for the transition to severe diabetic nephropathy.","authors":"Mariko Maekawa, Tatsuya Maekawa, Tomohiko Sasase, Takeshi Wakashima, Atsuhiro Uemura, Kinuko Uno, Takeshi Ohta, Takahisa Yamada","doi":"10.1538/expanim.22-0168","DOIUrl":"10.1538/expanim.22-0168","url":null,"abstract":"Diabetic nephropathy (DN), included in diabetic kidney disease (DKD), is a primary driver of end-stage renal disease (ESRD) leading to dialysis treatment. To develop new therapeutic drugs to prevent ESRD and avoid dialysis treatment, insight into DKD pathophysiology and animal models suitable for drug efficacy testing are needed. In this study, transcriptome analysis of kidneys from 26-week-old and 35-week-old uninephrectomized (UNX) db/db mice was used to identify the pathways that affect the deterioration of renal function in db/db mice. Differentially expressed genes suggested that there was increased interferon (IFN)-γ signaling during the 26 to 35-week period. Modules that changed between 26 and 35 weeks of age extracted by weighted gene co-expression network analysis (WGCNA) suggested increased the tumor necrosis factor (TNF)-α and nuclear factor-kappa B (NF-κB) signaling pathway in component cells of glomeruli. The protein-protein interaction (PPI) network analysis identified Cxcl16 as a hub gene for those signaling pathways, and it was shown that the pathways in this module changed when the glomerular filtration rate decreased in patients with DN. These results suggested the possibility that signaling mediated by Cxcl16 induced by IFN-γ and TNF-α between 26 and 35 weeks of age leads to renal fibrosis, resulting in severe disease. Drugs that target such pathways can be options for developing drugs for DN. We also think that the uninephrectomized db/db mouse can be used as an animal model of severe DKD and to evaluate efficacy in patients with DN.","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"29-40"},"PeriodicalIF":2.4,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10877145/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9860272","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

Null mutation of exocyst complex component 3-like does not affect vascular development in mice. 外囊复合体 3-like 成分的无效突变不会影响小鼠的血管发育。

IF 2.4 4区农林科学

Experimental Animals Pub Date : 2024-02-14 Epub Date: 2023-09-01 DOI: 10.1538/expanim.23-0105

Satsuki Takashima, Eiichi Okamura, Yusuke Ichiyama, Kiyoto Nishi, Akio Shimizu, Chisato Watanabe, Masanaga Muto, Shoma Matsumoto, Setsuko Tsukiyama-Fujii, Tomoyuki Tsukiyama, Hisakazu Ogita, Eiichiro Nishi, Masahito Ohji, Fumihiro Sugiyama, Satoru Takahashi, Seiya Mizuno, Ken-Ichi Mizutani, Masatsugu Ema

{"title":"Null mutation of exocyst complex component 3-like does not affect vascular development in mice.","authors":"Satsuki Takashima, Eiichi Okamura, Yusuke Ichiyama, Kiyoto Nishi, Akio Shimizu, Chisato Watanabe, Masanaga Muto, Shoma Matsumoto, Setsuko Tsukiyama-Fujii, Tomoyuki Tsukiyama, Hisakazu Ogita, Eiichiro Nishi, Masahito Ohji, Fumihiro Sugiyama, Satoru Takahashi, Seiya Mizuno, Ken-Ichi Mizutani, Masatsugu Ema","doi":"10.1538/expanim.23-0105","DOIUrl":"10.1538/expanim.23-0105","url":null,"abstract":"Exocyst is an octameric protein complex implicated in exocytosis. The exocyst complex is highly conserved among mammalian species, but the physiological function of each subunit in exocyst remains unclear. Previously, we identified exocyst complex component 3-like (Exoc3l) as a gene abundantly expressed in embryonic endothelial cells and implicated in the process of angiogenesis in human umbilical cord endothelial cells. Here, to reveal the physiological roles of Exoc3l during development, we generated Exoc3l knockout (KO) mice by genome editing with CRISPR/Cas9. Exoc3l KO mice were viable and showed no significant phenotype in embryonic angiogenesis or postnatal retinal angiogenesis. Exoc3l KO mice also showed no significant alteration in cholesterol homeostasis or insulin secretion, although several reports suggest an association of Exoc3l with these processes. Despite the implied roles, Exoc3l KO mice exhibited no apparent phenotype in vascular development, cholesterol homeostasis, or insulin secretion.","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"93-100"},"PeriodicalIF":2.4,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10877151/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10202084","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