{"title":"Diacerein alleviates endometrial fibrosis in an intrauterine adhesion model via ferroptosis inhibition.","authors":"Cong Shi, Jianhua Sun, Jumin Niu","doi":"10.1538/expanim.26-0015","DOIUrl":"https://doi.org/10.1538/expanim.26-0015","url":null,"abstract":"<p><p>Intrauterine adhesion (IUA) is a significant contributor to uterine infertility, primarily characterized by endometrial fibrosis. Although diacerein exhibits anti-inflammatory and anti-fibrotic properties, its therapeutic potential in IUA remains unclear. This study investigated the protective effects of diacerein in an IUA rat model induced by mechanical injury. Histological analysis revealed that diacerein treatment alleviated endometrial damage, and immunohistochemical staining confirmed the restoration of CK19 and CK18 expression, indicating improved epithelial integrity and regeneration. Diacerein mitigated endometrial fibrosis by inhibiting epithelial-mesenchymal transition (EMT), as evidenced by increased E-cadherin and decreased N-cadherin expression, likely via suppression of TGFβ/SMAD2 signaling. Diacerein exerted anti-inflammatory effects in IUA rats. Notably, diacerein inhibited ferroptosis by reducing lipid peroxidation, limiting Fe²⁺ accumulation, and modulating ferroptosis-related proteins, including ACSL4, SLC7A11, GPX4, and FTH1. The protective effects of diacerein were mirrored by ferroptosis inhibitor Ferrostatin-1 treatment but reversed by ferroptosis inducer Erastin, confirming that diacerein alleviates endometrial fibrosis in IUA rats through ferroptosis suppression. Mechanistically, diacerein modulated the NRF2/HMGB1 signaling pathway, restoring NRF2 and HO1 levels while downregulating HMGB1 expression. Collectively, these findings suggest that diacerein effectively attenuates ferroptosis-mediated fibrosis in IUA, highlighting ferroptosis inhibition as a promising therapeutic strategy for IUA management.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835476","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}
Limin Li, Cai Zhang, Lu Chen, Wenchao Yao, Xiaoli Hou, Zhengxiao Li, Faming Tian
{"title":"Keratinocyte-specific STAT3 knockout attenuates imiquimod-induced psoriasiform phenotype in mice.","authors":"Limin Li, Cai Zhang, Lu Chen, Wenchao Yao, Xiaoli Hou, Zhengxiao Li, Faming Tian","doi":"10.1538/expanim.26-0047","DOIUrl":"https://doi.org/10.1538/expanim.26-0047","url":null,"abstract":"<p><p>Signal transducer and activator of transcription 3 (STAT3) is critical in psoriasis, but keratinocyte-derived STAT3 remains unclear. This study investigated the effect of keratinocyte-specific STAT3 knockout on imiquimod (IMQ)-induced psoriasis-like dermatitis. Keratinocyte-specific STAT3 knockout (cKO) mice and littermate controls (LC) received daily topical 5% IMQ to induce psoriasis-like lesions. Lesion severity was assessed by PASI score, histopathology by H&E staining, and systemic inflammation by spleen index and serum CXCL1, CCL20, and IL-22 levels (ELISA). Skin expression of inflammation, chemokine, and STAT3 pathway related factors was examined by IHC, qRT-PCR, and Western blot. In vitro, IL-17A‑stimulated HaCaT cells were used with siRNA-mediated STAT3 knockdown; changes in STAT3 signaling and downstream factors were assessed by qRT-PCR and Western blot. In vivo, keratinocyte-specific STAT3 knockout significantly alleviated IMQ-induced skin lesions, reduced PASI score, improved barrier function, decreased spleen index, and lowered serum CXCL1, CCL20, and IL-22. It also suppressed IL-22, CXCL1, and CCL20 expression in skin and inhibited STAT3 activation. In vitro, IL-17A increased STAT3 phosphorylation, which was blocked by STAT3 knockdown, along with suppression of IL-22 and CXCL1 upregulation.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147766559","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}
{"title":"Nicardipine co-administered with medetomidine-midazolam-butorphanol anesthesia attenuates post-anesthetic hypothermia in rats.","authors":"Takeru Sasaki, Masaki Watanabe, Eisuke Hishida, Tomoki Omori, Ryuya Nakagawa, Riyu Inoue, Nobuya Sasaki","doi":"10.1538/expanim.26-0024","DOIUrl":"https://doi.org/10.1538/expanim.26-0024","url":null,"abstract":"<p><p>Medetomidine-midazolam-butorphanol (MMB) anesthesia is widely used in laboratory rodents but is frequently accompanied by peri- and post-anesthetic hypothermia. This study examined whether co-administration of nicardipine could attenuate hypothermia associated with MMB anesthesia in rats, thereby testing the concept that modulation of peripheral vascular tone can complement thermal management. Rats received MMB alone (0Ni) or MMB combined with nicardipine at 0.25 or 0.5 mg/kg. Body temperature was assessed under warmed and non-warmed conditions, and systolic blood pressure (SBP) and heart rate (HR) were monitored to evaluate cardiovascular effects. Under warmed conditions, body temperature profiles did not differ among groups. Under non-warmed conditions, however, nicardipine-treated rats maintained higher body temperatures during recovery, and both nicardipine groups showed significantly higher recovery-phase AUC values than the 0Ni group. Nicardipine did not significantly alter induction or recovery timing. In parallel, nicardipine produced a dose-dependent reduction in SBP and an increase in HR, particularly at 0.5 mg/kg. These findings suggest that nicardipine partially attenuates post-anesthetic hypothermia during recovery from MMB anesthesia under non-warmed conditions and may serve as a complementary approach to thermal management. However, the marked SBP reduction observed at 0.5 mg/kg warrants caution in practical application.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147766674","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}
{"title":"Menstrual cycles, lifespan, and anti-Müllerian hormone in cynomolgus monkeys.","authors":"Akie Takebayashi, Shunichiro Tsuji, Tadashi Sankai, Chizuru Iwatani, Hideaki Tsuchiya, Masatsugu Ema, Takashi Murakami","doi":"10.1538/expanim.25-0098","DOIUrl":"10.1538/expanim.25-0098","url":null,"abstract":"<p><p>The cynomolgus monkey (Macaca fascicularis) is an important experimental animal; however, its menstrual patterns, lifespan, and age-related changes in anti-Müllerian hormone (AMH) levels remain poorly characterized. This study aimed to analyze these factors and evaluate the usefulness of Cynomolgus monkeys in ovarian function research. The age at menarche was examined in 21 cynomolgus monkeys, and the age at menopause and age at death were tracked in another 22 postmenopausal monkeys. In addition, AMH levels were analyzed in 74 cynomolgus monkeys aged 0 to 33 years to evaluate ovarian reserve throughout their lives. Results showed a mean age at menarche of 3.69 ± 2.51 years, menopause at 27.00 ± 2.50 years, and a mean age at death of 32.04 ± 5.33 years. AMH levels throughout life showed a weak negative correlation with age. These findings suggest that changes in ovarian reserve throughout the life span of cynomolgus monkeys are similar to those in humans. To our knowledge, this study is the first to analyze menstruation, lifespan, and lifelong AMH levels in cynomolgus monkeys. Ovarian function throughout life, including childhood and postmenopause, was similar to that in humans, suggesting cynomolgus monkeys may be a useful experimental model.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"234-240"},"PeriodicalIF":1.2,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13100698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145803628","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":"PacBio long-read amplicon sequencing of dog leukocyte antigen genes at full-length level in beagle dogs.","authors":"Hiroya Konno, Jiro Miyamae, Rei Kajitani, Kazuto Kugou, Hiroko Kataoka, Makoto Akai, Tomomichi Ishizaka, Katsuyoshi Chiba","doi":"10.1538/expanim.25-0111","DOIUrl":"10.1538/expanim.25-0111","url":null,"abstract":"<p><p>The major histocompatibility complex (MHC) plays a critical role in individual immune responses and susceptibility to various conditions, including autoimmune diseases and drug reactions. In dogs, the canine MHC (dog leukocyte antigen, DLA) polymorphism is key to understanding immune mechanisms, but technical challenges have impeded its comprehensive genetic analysis. This study addressed these issues by using a novel DLA genotyping method combining long-range PCR and PacBio single-molecule real-time sequencing to analyze the full-length DLA class I and II gene sequences in 83 beagle dogs from two different strains (TOYO and Marshall), which are commonly used as laboratory animals. As a result of genotyping using the full-length sequences, 9, 5, 2, 6, and 8 extended alleles were newly discovered for the DLA class I genes in DLA-88, DLA-12, DLA-88L, DLA-64, and DLA-79, respectively. For the DLA class II genes, 11, 18, 12, and 8 extended alleles were newly discovered in DLA-DRA, DLA-DRB1, DLA-DQA1, and DLA-DQB1, respectively. There were 25 haplotypes consisting of extended alleles, in contrast to only 10 haplotypes classified using only peptide binding site sequences. Furthermore, comparisons between the strains revealed differences in haplotype frequencies and genetic differentiation. The full-length analysis also provided preliminary insights into regulatory elements, such as promoter and CpG island polymorphisms in DLA-DQB1. The results of this research have important implications for the understanding of the relationship between DLA polymorphism at full length and individual immune responses in dogs.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"250-261"},"PeriodicalIF":1.2,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13100700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145984880","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":"Integrative network pharmacology and experimental study of Qingda granule in hypertension-induced endothelial dysfunction.","authors":"Yanyan Yang, Qiurong Xie, Jingyi Zeng, Meizhu Wu, Daxin Chen, Wenqiang Zhang, Chenyu Lai, Aling Shen, Dawei Lian, Jun Peng","doi":"10.1538/expanim.25-0080","DOIUrl":"10.1538/expanim.25-0080","url":null,"abstract":"<p><p>Endothelial dysfunction (ED) plays a pivotal role in the pathogenesis of hypertension and its associated vascular complications. Qingda granule (QDG) exhibits significant antihypertensive properties and demonstrates therapeutic potential in ameliorating vascular dysfunction. This study aimed to explore QDG's role in alleviating endothelial injury in hypertension. An L-NAME (Nω-Nitro-L-arginine methyl ester)-induced hypertensive mouse model was used to evaluate the effects of QDG on blood pressure and endothelial function. Endothelial function was assessed through histological analysis, nitric oxide (NO) quantification, and vascular response measurements. To explore underlying mechanisms, network pharmacology was conducted using databases such as HERB, SwissTargetPrediction and STRING. Key pathways related to inflammation and cell adhesion were identified. Based on these findings, immunohistochemical staining was conducted to analyze the expression of phosphorylation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65 (p-NF-κB p65), NF-κB p65, intercellular adhesion molecule-1 (ICAM-1), and tumor necrosis factor-α (TNF-α) in vascular tissues. QDG treatment significantly reduced blood pressure, increased NO levels, and enhanced endothelial nitric oxide synthase (eNOS) expression in L-NAME-induced hypertensive mice, indicating its potential to restore endothelial function. Experimental validation further confirmed that QDG markedly suppressed the expression of p-NF-κB p65, TNF-α, and ICAM-1 in vascular tissues. These results suggest that QDG alleviates hypertension-induced ED primarily by inhibiting inflammation and endothelial adhesion via the NF-κB signaling pathway. Overall, QDG presents a promising therapeutic candidate for managing hypertension and its vascular complications.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"131-143"},"PeriodicalIF":1.2,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13100706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145400285","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 : 2026-04-22Epub Date: 2025-10-25DOI: 10.1538/expanim.25-0047
Kazuaki Takahashi, Norio Hike, Hiroyuki Ogura, Takayuki Okamura, Dai Yamamoto, Junko Sato
{"title":"Body weight loss without reduction in food consumption observed in cynomolgus monkeys during non-clinical toxicity studies.","authors":"Kazuaki Takahashi, Norio Hike, Hiroyuki Ogura, Takayuki Okamura, Dai Yamamoto, Junko Sato","doi":"10.1538/expanim.25-0047","DOIUrl":"10.1538/expanim.25-0047","url":null,"abstract":"<p><p>In pharmaceutical development, weight loss is occasionally observed in monkeys during non-clinical toxicity studies and can be difficult to differentiate from drug effects. This study retrospectively analyzed data from control group monkeys without drug treatment to investigate the incidence of weight loss and its physiological and pathological characteristics. We also investigated potential improvements through enhanced animal welfare. In the 4- and 13-week toxicity studies conducted at the test facility from 2010 to 2022, 684 control group monkeys were investigated. Among them, 3 animals in the 4-week toxicity studies and 5 animals in the 13-week toxicity studies showed a weight change rate of less than -10%, resulting in an incidence rate of 1.2%. However, these animals had adequate food consumption. Animals in the 4-week toxicity studies showed signs of stress in histopathology. Additionally, 2/3 animals in the 4-week toxicity studies had decreased blood glucose levels and 1/5 animal in the 13-week toxicity study fell into a crouching posture, suggesting hypoglycemia that was alleviated with glucose administration, indicating stress-induced metabolic abnormalities. From 2015, an enrichment program was implemented to improve animal welfare. Prior to this program, 2.4% of animals showed a weight change rate of less than -10%, which dropped to 0.25% post-implementation, suggesting the program's effectiveness in reducing stress. These results clarify the characteristics of animals that lose weight during toxicity studies and suggest that improving animal welfare can reduce the incidence rate.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"121-130"},"PeriodicalIF":1.2,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13100701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145372217","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 : 2026-04-22Epub Date: 2025-11-05DOI: 10.1538/expanim.25-0060
Jonna Rose C Maniwang, Yulan Tang, Mark Joseph M Desamero, Chen Wang, Wataru Fujii, Dunfu Eer, Shigeru Kyuwa, James K Chambers, Kazuyuki Uchida, Yuri Kominami, Hideki Ushio, Cleofas R Cervancia, Maria Amelita C Estacio, Shigeru Kakuta
{"title":"Stingless bee propolis promotes hair follicle regeneration and melanocyte function in chemotherapy-induced alopecia mouse model.","authors":"Jonna Rose C Maniwang, Yulan Tang, Mark Joseph M Desamero, Chen Wang, Wataru Fujii, Dunfu Eer, Shigeru Kyuwa, James K Chambers, Kazuyuki Uchida, Yuri Kominami, Hideki Ushio, Cleofas R Cervancia, Maria Amelita C Estacio, Shigeru Kakuta","doi":"10.1538/expanim.25-0060","DOIUrl":"10.1538/expanim.25-0060","url":null,"abstract":"<p><p>Chemotherapy-induced alopecia (CIA) is one of the most apparent symptoms of side effects in a cancer patient undergoing chemotherapy using anti-cancer drugs, resulting in distress and a lower quality of life. Hence, this study investigated the protective and regenerative effects of Philippine stingless bee propolis on CIA in a murine model. Female C57BL/6N mice were subjected to hair cycle synchronization through depilation, followed by cyclophosphamide (CYP) administration to induce hair loss and graying. Daily topical application of 99.5% ethanol extracted propolis diluted twice with water was performed for 30 days. Results revealed that propolis-treated mice exhibited increased folliculogenesis and epidermal thickness, but not hair length, and improved melanogenesis compared to controls. Immunohistochemical and gene expression analyses revealed increased Ki67<sup>+</sup> proliferative cells and reduced apoptosis (TUNEL<sup>+</sup> cells) at the early 48 h of topical treatment. Moreover, propolis upregulated expressions of Lef1 and melanogenic genes (Tyr, Tyrp1, Dct) at 30 days of treatment. These findings suggest that Philippine stingless bee propolis promotes hair follicle regeneration and melanocyte function, offering a potential natural therapeutic approach for CIA.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"156-171"},"PeriodicalIF":1.2,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13100695/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145451388","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":"Hematologic and biochemical changes associated with age and strain in aged B6 mice breeding in the national center of geriatrics and gerontology.","authors":"Julio A Almunia, Yoshiko Munesue, Noboru Ogiso, Shunsuke Yuri, Haruka Kawasaki, Nobuko Morikawa, Satoko Noma, Kazumichi Takano, Atsushi Watanabe, Shumpei Niida, Akihiko Nishikimi","doi":"10.1538/expanim.25-0071","DOIUrl":"10.1538/expanim.25-0071","url":null,"abstract":"<p><p>At the National Center of Geriatric and Gerontology (NCGG), aged mice and rats are used in research on aging and the treatment and prevention of gerontological diseases. Some of the most commonly used mouse strains in our center and general research were the C57BL/6J (B6J) and C57BL/6N (B6N). In this study, hematological and biochemical changes related to age, strain, and sex, from 3 months (mo) to 24 mo, were characterized every 3 mo in the B6J and B6N strains. Hematological results showed that in B6J males at 24 mo, the levels of WBC, especially lymphocytes, were higher than in the B6N strain. In males B6J, the number of CD4+ T cells did not decrease significantly between 6 and 24 mo, but in females and strain B6N, the number of CD4+ T cells decreased significantly. The levels of red blood cells (RBC) and hemoglobin (HGB) were reduced with age in all strains, while the number of platelets (PLT) increased. Biochemical parameters, Blood urea nitrogen (BUN) and Creatinine (CRE) in B6J males were significantly higher than in the other groups at 24 mo. Glutamate oxalacetate transaminase/aspartate aminotransferase (GOT/AST) and glutamate pyruvate transaminase/alanine aminotransferase (GPT/ALT) levels were higher in the B6N strain than the B6J strain at 24 mo. The present results revealed significant variations in hematological and biochemical parameters between the two strains and between sexes as a result of genetic and hormonal differences in laboratory mice.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"172-193"},"PeriodicalIF":1.2,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13100696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145451400","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":"A nonsense mutation in the Mocos gene induces xanthinuria, obstructive nephropathy, and anemia in rats.","authors":"Mao Urasaki, Kana Nagasaka, Minori Kido, Kenta Hayashi, Ayumi Watanabe, Kosuke Hattori, Takahiro Sekiguchi, Mitsuru Kuwamura, Miyuu Tanaka, Tomoji Mashimo, Takashi Kuramoto","doi":"10.1538/expanim.25-0127","DOIUrl":"10.1538/expanim.25-0127","url":null,"abstract":"<p><p>Xanthinuria type II is a rare hereditary disorder caused by mutations in the MOCOS gene, leading to dual deficiency of xanthine dehydrogenase and aldehyde oxidase. To establish a robust animal model for this condition, we generated Mocos knock-in (KI) rats carrying the Arg419Ter nonsense mutation identified in Japanese patients. Homozygous KI rats exhibited severe growth retardation, anemia, and reduced survival, with all individuals dying by 14 weeks of age. Biochemical analyses revealed elevated levels of hypoxanthine and xanthine, along with decreased uric acid in both serum and urine, confirming xanthinuria. Homozygous KI rats also showed increased blood creatinine (CRE) and urea nitrogen (UN), and decreased urinary CRE and UN, indicating renal dysfunction. Histopathological examination showed obstructive nephropathy characterized by tubular atrophy, crystal deposition, and inflammation. Compared to existing mouse models, Mocos KI rats demonstrated extended lifespan, enabling more detailed investigation of disease mechanisms. This rat model provides a valuable tool for studying the pathogenesis of xanthinuria type II and exploring potential therapeutic strategies.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"202-213"},"PeriodicalIF":1.2,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13100697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145667851","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}