Lab Animal最新文献

{"title":"Metabolism drives sex bias in fly gut infection","authors":"Alexandra Le Bras","doi":"10.1038/s41684-026-01781-y","DOIUrl":"10.1038/s41684-026-01781-y","url":null,"abstract":"","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":"55 8","pages":"283-283"},"PeriodicalIF":6.8,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148617435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Generation and characterization of humanized CD4 knock-in mice expressing chimeric mouse/human CD4 protein","authors":"Ka-Man Kam, Tsz-En Shiu, Chien-Ming Hsieh, Wen-Ting Lu, Yu-Yun Pan, Chia-I Lin, Pin-Hung Lin, Ya-Hui Chuang, I-Shing Yu, Pei-Lung Chen","doi":"10.1038/s41684-026-01775-w","DOIUrl":"10.1038/s41684-026-01775-w","url":null,"abstract":"Humanized mouse models have become indispensable tools for investigating human gene function and disease modeling. However, conventional transgenic approaches carry the risk of unforeseen biological consequences. Here, to address this concern, we developed a novel human CD4 knock-in (hCD4 KI) mouse model using CRISPR–Cas9 gene-editing technology. We replaced the region encoding the first two major extracellular domains of the mouse Cd4 gene, which are critical for interaction with major histocompatibility complex (MHC) class II, with the corresponding human CD4 sequence. Subsequently, we conducted comprehensive physiological and immune system analyses on hCD4 KI mice, including both heterozygous (CD4m/h) and homozygous (CD4h/h) genotypes. Our investigations revealed a dosage-dependent impact of the hCD4 KI, resulting in a decreased percentage of CD4+ single-positive cells, accompanied by a corresponding increase in CD8+ single-positive cells within the thymus. These developmental alterations, evident in the thymus, were also observed in the peripheral lymphatic system such as the spleen and in the peripheral blood, exhibiting an increased population of mature CD8+ T cells and a decreased proportion of mature CD4+ T cells. Despite these changes, hCD4 KI mice exhibited normal biological characteristics, including T cell activation and proliferation functions, blood composition, tissue structure and body weight, closely resembling those of wild-type (CD4m/m) mice. Our study underscores hCD4 KI mice as a valuable tool for exploring CD4 and MHC class II interactions, with potential for future integration with humanized MHC class II KI mice, offering insights into immune disease mechanisms. CRISPR-engineered humanized CD4 knock-in mice expressing chimeric mouse/human CD4 protein maintain normal physiology, despite shifts in T cell populations, providing a robust model to study CD4–MHC class II interactions and immune disease mechanisms.","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":"55 10","pages":"402-412"},"PeriodicalIF":6.8,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148552292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Establishment and functional analysis of an inducible Apoc2-knockout mouse model to investigate the role of Apoc2 in normal hematopoiesis","authors":"Xiaochen Zhang, Ritu Chandwani, Mateusz Pospiech, Yiting Meng, Kanaka Dhuri, Atham Ali, Bhakti Thakker, Shephali Milind Kadam, Wenda Zhu, Yiyu Xiao, Denis Sviridov, Anna Wolska, Alan T. Remaley, Houda Alachkar","doi":"10.1038/s41684-026-01748-z","DOIUrl":"10.1038/s41684-026-01748-z","url":null,"abstract":"Apolipoprotein C2 (APOC2) has been identified as a potential therapeutic target for acute myeloid leukemia, but its impact on normal hematopoiesis remains unclear. Here we generated a global inducible Apoc2 knockout (KO) mouse model by breeding R26-CreERT2 mice with mice homozygous for Apoc2 lox sites (Apoc2fl/fl) over three generations. Global Apoc2 KO was induced in 4–8-week-old mice by 5 consecutive days of intraperitoneal administration of tamoxifen. Successful Apoc2 KO was confirmed by measuring Apoc2 mRNA levels, showing 80–99% reduction in the liver, bone marrow, spleen and blood tissues compared with wild type (WT). Despite significantly higher serum triglyceride levels in the Apoc2-KO group, no apparent abnormal phenotypes were observed. In vitro expansion of the hematopoietic stem and progenitor cells and splenocytes from Apoc2-KO were comparable to that of WT mice. In addition, Apoc2 deletion did not significantly affect the colony-forming ability or the competitive repopulation ability of hematopoietic stem and progenitor cells. Hematological analysis revealed no significant differences between Apoc2-KO and WT mice. RNA-sequencing analysis of bone marrow samples from the Apoc2-KO group identified four significantly downregulated genes and five upregulated genes, including Gm16867, which is orthologous to the human SLC25A37 gene involved in mitochondrial iron homeostasis. Gene set enrichment analysis revealed the enrichment of heme metabolism (false discovery rate 0.077). Our study demonstrates that deletion of Apoc2 exhibits limited impact on normal hematopoiesis under normal conditions. Future characterization of this Cre-inducible Apoc2-KO mice under stress conditions or during aging is needed to fully demonstrate the biological impact of Apoc2 deletion. This study shows that inducible global deletion of Apoc2 in mice causes hypertriglyceridemia but has minimal impact on normal hematopoiesis, supporting APOC2 as a potential therapeutic target with limited baseline hematopoietic risk.","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":"55 9","pages":"354-366"},"PeriodicalIF":6.8,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41684-026-01748-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148416030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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":"Structural osteoarthritis pathogenesis correlates with distinct pain and dysfunction profiles after ACL injury in rats","authors":"Nicholas M. Pancheri, Nisha Kyathsandra, Jake Heinonen, Emily Sverdrup, Sanique M. South, Sruthi Ranganathan, Kaitlyn A. Link, Angela SP Lin, Nick J. Willett, Robert E. Guldberg","doi":"10.1038/s41684-026-01762-1","DOIUrl":"10.1038/s41684-026-01762-1","url":null,"abstract":"Post-traumatic osteoarthritis (PTOA) frequently arises following knee injury, such as anterior cruciate ligament (ACL) rupture. Small animal models are critical for studying PTOA pathology and translating therapeutic interventions. Here our objective was to identify key structural PTOA pathologies and evaluate their associations with aberrant pain and function after a clinically relevant ACL injury in a small animal model. This work leveraged a suite of quantitative cartilage and bone analysis techniques using high-resolution contrast-enhanced microcomputed tomography to investigate the associations between pain-related behaviors and structural osteoarthritis pathogenesis throughout the knee joint in rats. We hypothesized that ACL rupture would increase pain sensitization and limb dysfunction and that this would correlate with the development of clinically relevant osteophytes and cartilage lesions at moderate (4 weeks) and severe disease stages (8 weeks). We showed that ACL rupture induced hyperalgesia and prolonged hindlimb weight-bearing dysfunction; these pain-related behaviors were strongly correlated with changes in the tibiofemoral subchondral bone plate, but not with osteophyte formation. Moreover, we show that patella bone pathology correlates strongly with pain sensitivity and limb function. Joint degeneration initially manifested in the posterior aspect of the medial tibiofemoral compartments, as indicated by full-thickness femoral cartilage lesions and tibial osteophytes at 4 weeks and corresponding tibial cartilage hypertrophy and subchondral sclerosis by 8 weeks. The established outcome parameters and association of structural pathogenesis with pain and dysfunction provide a foundation for studying fundamental PTOA disease etiology and testing therapeutic efficacy in a rodent preclinical model. Anterior cruciate ligament rupture in rat induces pain sensitization and limb dysfunction, correlating with tibiofemoral subchondral and patellar bone changes. These findings provide new insights into post-traumatic osteoarthritis disease etiology.","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":"55 9","pages":"344-353"},"PeriodicalIF":6.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41684-026-01762-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148365016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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":"Astrocyte metabolic dynamics drive pain persistence","authors":"Alexandra Le Bras","doi":"10.1038/s41684-026-01765-y","DOIUrl":"10.1038/s41684-026-01765-y","url":null,"abstract":"","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":"55 7","pages":"246-246"},"PeriodicalIF":6.8,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41684-026-01765-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148349859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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":"Role of ceramides in cancer cachexia","authors":"Alexandra Le Bras","doi":"10.1038/s41684-026-01768-9","DOIUrl":"10.1038/s41684-026-01768-9","url":null,"abstract":"","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":"55 7","pages":"243-243"},"PeriodicalIF":6.8,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148349870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NMDA-dependent mechanism of depression","authors":"Jorge Ferreira","doi":"10.1038/s41684-026-01766-x","DOIUrl":"10.1038/s41684-026-01766-x","url":null,"abstract":"","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":"55 7","pages":"247-247"},"PeriodicalIF":6.8,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41684-026-01766-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148349860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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":"Male reproductive phenotype in cystic fibrosis: comparison of existing animal models","authors":"Angèle Boursier, Charles-Henry Cottart, Aissatu Balde-Camara, François Vialard, Anne-Laure Barbotin","doi":"10.1038/s41684-026-01763-0","DOIUrl":"10.1038/s41684-026-01763-0","url":null,"abstract":"In men, cystic fibrosis (CF) leads to infertility in over 95% of cases, due to early and progressive atresia of the vas deferens, resulting in obstructive azoospermia. The advent of highly effective modulator therapy has enabled more men with CF to consider parenthood, raising important questions regarding the impact of these treatments on male fertility. Animal models provide major insights into the mechanism of CF-related reproductive tract abnormalities, yet high interspecies variability complicates model selection. Mouse models display heterogeneous phenotype: knock-in or partial knockout models usually remain fertile, whereas complete knockouts may develop vas deferens atresia with aging. Among currently studied models, CF transmembrane conductance regulator (CFTR)-knockout rats more closely reproduce the human phenotype, showing bilateral absence of the vas deferens and epididymal hypoplasia, although they exhibit more pronounced hypospermatogenesis than observed in men. In larger animal models, including ferrets, pigs, sheep and rabbits, absence of the vas deferens duct and epididymis is frequently observed, often with normal testicular histology; however, most studies in these species have mainly focused on neonatal stages, leaving long-term reproductive outcomes uncharacterized. No single model fully replicates human male reproductive pathology in CF. Combining rodent and large-animal models is probably essential to elucidate the mechanisms of vas deferens absence and to assess the long-term effects of CFTR modulators on male spermatogenesis and reproductive outcomes. This Review discusses how animal models recapitulate male infertility in cystic fibrosis and highlights the need for combined rodent and large-animal studies to investigate reproductive pathology and the effects of highly effective modulator therapy.","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":"55 10","pages":"379-385"},"PeriodicalIF":6.8,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41684-026-01763-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148361041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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":"Postweaning exercise improves sleep deprivation effects","authors":"Jorge Ferreira","doi":"10.1038/s41684-026-01773-y","DOIUrl":"10.1038/s41684-026-01773-y","url":null,"abstract":"","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":"55 7","pages":"244-244"},"PeriodicalIF":6.8,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148349867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Environmental enrichment modulates the mouse immune system","authors":"Jorge Ferreira","doi":"10.1038/s41684-026-01771-0","DOIUrl":"10.1038/s41684-026-01771-0","url":null,"abstract":"","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":"55 7","pages":"244-244"},"PeriodicalIF":6.8,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148349866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}