{"title":"Biochemical and hematological reference intervals in rhesus and cynomolgus macaques and implications for vaccine and drug development","authors":"Xianglei Yan, Rodrigo Arcoverde Cerveira, Sebastian Ols, Klara Lenart, Fredrika Hellgren, Marcos Miranda, Olivia Engstrand, Annika Reinhardt, Bengt Eriksson, Karin Loré","doi":"10.1038/s41684-025-01547-y","DOIUrl":"https://doi.org/10.1038/s41684-025-01547-y","url":null,"abstract":"<p>Nonhuman primates have a key role in the evaluation of novel therapeutics including vaccine and drug development. Monitoring biochemical and hematological parameters of macaques is critical to understand toxicity and safety, but general reference intervals following standardized guidelines remain to be determined. Here we compiled multiple internal datasets to define normal ranges of classical biochemical and hematological parameters in Indian and Chinese rhesus macaques as well as cynomolgus macaques. Furthermore, the combination of hematological data with phenotypic information of cells obtained by flow cytometry enabled analyses of specific immune cell subsets. We found that vaccination generally induced transient changes at 24 h in cell frequencies accompanied by fluctuation in selected liver enzymes and metabolites. However, most parameters remained within our identified reference intervals. These deviations did not lead to noticeable side effects. Fluctuation in selected biochemical and hematological parameters was accompanied with differentiation of CD14<sup>+</sup>CD16<sup>+</sup> intermediate monocytes and upregulation of genes associated with interleukin-1 signaling. By contrast, two animals with noticeable side effects showed sustained deviations. This study provides insights into baseline and vaccine-induced biochemical and hematological profiles of healthy macaques, facilitating the interpretation of toxicity and safety assessments in preclinical trials of novel therapies.</p>","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":"233 1","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144066938","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}
Lab AnimalPub Date : 2025-05-02DOI: 10.1038/s41684-025-01553-0
Jorge Ferreira
{"title":"Non-invasive detection of Duchenne muscular dystrophy","authors":"Jorge Ferreira","doi":"10.1038/s41684-025-01553-0","DOIUrl":"https://doi.org/10.1038/s41684-025-01553-0","url":null,"abstract":"<p>Duchenne muscular dystrophy (DMD) is a severe, progressive muscle-wasting disease caused by mutations in the <i>DMD</i> gene, leading to a lack of dystrophin—a protein essential for stabilizing muscle cell membranes. The absence of dystrophin results in repeated muscle damage, degeneration and chronic inflammation. The canine model identified and characterized in 1988 remains the most widely used large-animal model for DMD research. However, studies of muscle inflammation have traditionally relied on invasive biopsies or necropsies, creating a need for minimally invasive approaches. A study in <i>Disease Models & Mechanisms</i> used a canine-specific Luminex assay—a multiplex immunoassay—to quantify 13 cytokines and chemokines inflammatory markers in frozen serum samples from normal and dystrophic dogs across various ages. Additionally, it evaluated the impact of sample storage (fresh vs. frozen) and type (serum vs. plasma) on cytokine measurements. From all the markers, only CCL2, a proinflammatory chemokine, showed consistent changes at all ages, with the most pronounced increase occurring between 3 and 9 months compared to healthy dogs. These results establish a foundation for using CCL2 as a robust non-invasive circulatory immune biomarker for monitoring DMD progression and assessing responses to experimental therapies.</p><p><b>Original reference:</b> Pérez-López, D. O. et al. <i>Dis. Model. & Mech</i>. <b>18</b>, dmm052137 (2025)</p>","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":"27 1","pages":"114-114"},"PeriodicalIF":6.9,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143901485","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}
Lab AnimalPub Date : 2025-05-02DOI: 10.1038/s41684-025-01549-w
Alexandra Le Bras
{"title":"Studying bovine TB in 3D","authors":"Alexandra Le Bras","doi":"10.1038/s41684-025-01549-w","DOIUrl":"https://doi.org/10.1038/s41684-025-01549-w","url":null,"abstract":"<p>Bovine tuberculosis (BTB), primarily caused by <i>Mycobacterium bovis</i>, is an important animal health and economic problem for the cattle industry and a potential zoonotic threat. Large animal models present practical and ethical limitations, calling for alternative experimental models to study BTB pathogenesis and identify therapies. In a new study in <i>Communications Biology</i>, researchers from the National Institute of Animal Biotechnology in Hyderabad report the development of an ex vivo bovine pulmosphere model that recapitulates TB infection, including host responses during the early stage of infection. The pulmospheres, created from primary lung cells isolated from cattle lung tissue from slaughterhouses, encompassed macrophages, epithelial cells, fibroblasts, alveolar cells and other immune cells together with diverse extracellular matrix components. Transcriptomic and proteomic analyses revealed that infection with <i>M. bovis</i> BCG, an attenuated vaccine strain, and <i>M. tuberculosis</i> H37Rv, a laboratory-adapted human clinical strain, upregulated key host pathways in the pulmospheres, but with pathogen-specific variations. This new bovine 3D pulmosphere model could have important implications for biomarker discovery, drug screening and TB control strategies.</p><p><b>Original reference:</b> Bhaskar, V. et al<i>. Commun. Biol</i>. <b>8</b>, 559 (2025)</p>","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":"18 1","pages":"113-113"},"PeriodicalIF":6.9,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143901486","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}
Lab AnimalPub Date : 2025-05-02DOI: 10.1038/s41684-025-01556-x
Jorge Ferreira
{"title":"Pathogenic role of Arhgef18 in cardiomyopathies","authors":"Jorge Ferreira","doi":"10.1038/s41684-025-01556-x","DOIUrl":"https://doi.org/10.1038/s41684-025-01556-x","url":null,"abstract":"<p>Cardiomyopathies (CMs), including dilated, hypertrophic and left-ventricular noncompaction types, are common yet poorly understood myocardial diseases in children, with genetic factors explaining only a third of cases. A study in <i>Disease Models & Mechanisms</i> investigates the role of Rho/Rac guanine nucleotide exchange factor 18 (<i>Arhgef18)</i>, a gene previously identified as having a potential role in CM pathogenesis, by developing a cardiomyocyte-specific <i>Arhgef18</i> conditional knockout (cKO) mouse model using the Cre/LoxP system. These mice exhibited hallmark CM phenotypes, including ventricular dilation wall thinning, and reduced cardiac function compared to control animals. Notably, cytoskeletal remodeling and loss of cardiomyocyte polarity were observed, suggesting that <i>Arhgef18</i> is critical for maintaining myocardial structure and organization. Tissue-specific analysis confirmed that <i>Arhgef18</i> was specifically knocked down in heart tissue, with no change in other organs. The findings highlight <i>Arhgef18</i> as a potential pathogenic gene contributing to CM through its role in cytoskeletal integrity and polarity regulation. This model provides a stable and reliable platform for exploring CM mechanisms and offers foundational insights for developing targeted diagnostic and therapeutic strategies for pediatric cardiomyopathies.</p><p><b>Original reference:</b> Fu, X. et al. <i>Dis. Model. & Mech</i>. <b>18</b>, dmm052172 (2025)</p>","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":"112 1","pages":"114-114"},"PeriodicalIF":6.9,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143901488","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}
Lab AnimalPub Date : 2025-05-02DOI: 10.1038/s41684-025-01554-z
Jorge Ferreira
{"title":"New OCD suppression target","authors":"Jorge Ferreira","doi":"10.1038/s41684-025-01554-z","DOIUrl":"https://doi.org/10.1038/s41684-025-01554-z","url":null,"abstract":"<p>Obsessive-compulsive disorder (OCD) is a disabling psychiatric condition affecting up to 3% of the population, marked by intrusive thoughts and compulsive behaviors. Current treatments, such as selective serotonin reuptake inhibitors, are not universally effective. OCD pathology is linked to hyperactivity in corticostriatal-thalamic circuits and elevated glutamate:GABA ratios in brain regions like the anterior cingulate cortex. A study in <i>Psychopharmacology</i> analyzes the potential of targeting glutamatergic signaling via metabotropic glutamate receptors to reduce compulsive behaviors in male Lister-Hooded rats. Using the Observing Response Task after categorizing rats into groups that mimic OCD-like checking behavior, characterized by repetitive actions, researchers tested two compounds: the metabotropic glutamate receptor 2 (mGluR2) positive allosteric modulator AZD-8529 and the mGluR2/3 agonist LY404039 (pomaglumetad). Both drugs dose-dependently reduced excessive checking without impairing reward-seeking behavior or cue-guided responses when compared with vehicle-treated animals. These findings indicate that mGluR2-targeting compounds can selectively and safely suppress compulsive-like checking, highlighting a promising new therapeutic avenue. This work supports further research of glutamatergic modulation in treating OCD, offering potential future treatment for patients unresponsive to conventional therapies.</p><p><b>Original reference:</b> McKenzie, C. et al. <i>Psychopharmacology</i> (2025). https://doi.org/10.1007/s00213-025-06774-2</p>","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":"44 1","pages":"114-114"},"PeriodicalIF":6.9,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143901489","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}
Lab AnimalPub Date : 2025-05-02DOI: 10.1038/s41684-025-01552-1
Alexandra Le Bras
{"title":"Valve function in Drosophila","authors":"Alexandra Le Bras","doi":"10.1038/s41684-025-01552-1","DOIUrl":"https://doi.org/10.1038/s41684-025-01552-1","url":null,"abstract":"<p>In vertebrates, which harbor a closed circulatory system, intracardiac valves regulate the directionality of blood flow and valve failure or dysfunction can result in diminished heart functionality. Compared to vertebrates, invertebrate hearts exhibit rather simple valves. In <i>Drosophila</i>, which like all insects, has an open circulatory system, each valve consists of two contralaterally located cells with a unique histology. To date, no report has described in detail the biomechanical functionality of valve cells in <i>Drosophila</i>. A new study in <i>PLoS Genetics</i> investigated the physiological consequences of cardiac valve malformation induced by genetic manipulation in <i>Drosophila</i>. The findings notably show that a reduction in deformation capability of valve cells in mutant flies decreased luminal opening, resulting in decreased transport and distribution of hemolymph in the body and impaired heart performance. This study highlights for the first time the physiological importance of cardiac valves in an invertebrate model organism and calls for further research on hemodynamics in insects and the role of valves cells in circulation.</p><p><b>Original reference:</b> Meyer, C. & Paululat, A. <i>PLoS Genet</i>. <b>21</b>, e1011613 (2025)</p>","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":"97 1","pages":"113-113"},"PeriodicalIF":6.9,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143901490","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}
Lab AnimalPub Date : 2025-05-02DOI: 10.1038/s41684-025-01555-y
Jorge Ferreira
{"title":"Aripiprazole intestinal side effects in flies","authors":"Jorge Ferreira","doi":"10.1038/s41684-025-01555-y","DOIUrl":"https://doi.org/10.1038/s41684-025-01555-y","url":null,"abstract":"<p>Aripiprazole, a third-generation antipsychotic, acts as a dopamine partial agonist and is generally better tolerated than older antipsychotics by humans. However, many patients report gastrointestinal side effects, the mechanisms of which remain unclear. A study in <i>Disease Models & Mechanisms</i> used <i>Drosophila melanogaster</i> to model the potential gut toxicity of aripiprazole, exploring the conserved drug metabolism pathways and well-characterized intestinal system. Oral aripiprazole exposure in flies caused mitochondrial dysfunction, leading to elevated reactive oxygen species (ROS) and activation of the JNK (c-Jun N-terminal kinase) signaling pathway, linked to cellular stress and death, specifically via the fly orthologue <i>basket</i> (bsk). Chronic JNK activation disrupted intestinal homeostasis, triggered apoptosis and led to gut tissue degeneration. Here, the gene <i>puckered</i>, a negative regulator of JNK signaling, was upregulated, confirming pathway engagement. Notably, supplementation with antioxidants mitigated these toxic effects. These findings link aripiprazole-induced gut toxicity to mitochondrial dysfunction and ROS-dependent JNK activation and suggest a mechanistic basis for the drug’s gastrointestinal side effects observed in patients.</p><p><b>Original reference:</b> Hurcomb, J.D. et al. <i>Dis. Model. & Mech</i>. <b>18</b>, dmm052180 (2025)</p>","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":"22 1","pages":"114-114"},"PeriodicalIF":6.9,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143901484","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}
Lab AnimalPub Date : 2025-05-02DOI: 10.1038/s41684-025-01550-3
Alexandra Le Bras
{"title":"Dogs and humans share obesity genes","authors":"Alexandra Le Bras","doi":"10.1038/s41684-025-01550-3","DOIUrl":"https://doi.org/10.1038/s41684-025-01550-3","url":null,"abstract":"<p>Obesity is a global health problem mainly attributed to environmental and lifestyle factors such as diet, low physical activity or socioeconomic factors. However, genetic factors also considerably contribute to weight-gain susceptibility. Although large-scale population genomic studies in humans have identified >1,000 loci associated with body mass index, effectively narrowing down candidate genes for further mechanistic studies has been challenging. Pet dogs represent a valuable model for studying the genetic basis of obesity because, like humans, they are experiencing an obesity pandemic (40-60% of pet dogs are classified as overweight or obese), and because modern breeds are genetically homogenous, making trait mapping highly tractable. To identify obesity genes, Wallis and colleagues performed a canine genome-wide association (GWAS) study for body condition score—a measure of obesity—in 241 Labrador retrievers, a dog breed prone to obesity. From the GWAS, they identified the gene DENN domain containing 1B (<i>DENND1B</i>) as an obesity gene in dogs and confirmed its relevance to human obesity using data from human studies. These findings demonstrate the benefits of studying complex diseases, including obesity, in nontraditional animal models, such as the dog.</p><p><b>Original reference:</b> Wallis, N.J. et al<i>. Science</i> <b>387</b>, eads2145 (2025)</p>","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":"40 1","pages":"113-113"},"PeriodicalIF":6.9,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143901483","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}
Lab AnimalPub Date : 2025-05-02DOI: 10.1038/s41684-025-01551-2
Alexandra Le Bras
{"title":"AAV toolkit for axolotl nervous system","authors":"Alexandra Le Bras","doi":"10.1038/s41684-025-01551-2","DOIUrl":"https://doi.org/10.1038/s41684-025-01551-2","url":null,"abstract":"<p>The axolotl, which can regenerate injuries to the central and peripheral nervous system, is an emerging model system to study neural circuit regeneration. Most findings in this model come from using classical tracers and imaging techniques, which present important limitations. Therefore, there is a need for new tools to efficiently label and/or manipulate cells in the axolotl nervous system and capture neural circuit regeneration. Studies in rodents and other mammals have frequently used recombinant adeno-associated viruses (AAVs) for targeted gene delivery in the nervous system, facilitating both circuit identification and functional circuit analysis. However, there are still no reports of AAV-mediated gene delivery to axolotl nervous system tissue. A new study in <i>PNAS</i> presents a set of AAV serotypes for efficient gene delivery in the axolotl nervous system, which could facilitate the study of nervous system regeneration. The findings notably show that while AAV8, AAV9, AAVRG and AAVPHP.eB are most suited to label neurons of the axolotl brain, AAV8, AAV9, and AAVPHP.eB are also suited to label cells of the spinal cord, with AAV9 being also the most suitable to label retinal cells.</p><p><b>Original reference:</b> Lust, K. & Tanaka, E.M. <i>Proc. Natl. Acad. Sci. USA</i> <b>122</b><i>,</i> e2421373122 (2025)</p>","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":"224 1","pages":"113-113"},"PeriodicalIF":6.9,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143901487","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}
Lab AnimalPub Date : 2025-05-01DOI: 10.1038/s41684-025-01557-w
Alexandra Le Bras
{"title":"Impact of intermittent fasting on male sexual behavior.","authors":"Alexandra Le Bras","doi":"10.1038/s41684-025-01557-w","DOIUrl":"https://doi.org/10.1038/s41684-025-01557-w","url":null,"abstract":"","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":"36 1","pages":"115"},"PeriodicalIF":6.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143903083","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}
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