Lucie O M Perillat, Tatianna W Y Wong, Eleonora Maino, Abdalla Ahmed, Ori Scott, Elzbieta Hyatt, Paul Delgado-Olguin, Shagana Visuvanathan, Evgueni A Ivakine, Ronald D Cohn
{"title":"Generation and characterization of a mouse model of Becker muscular dystrophy with a deletion of Dmd exons 52 to 55.","authors":"Lucie O M Perillat, Tatianna W Y Wong, Eleonora Maino, Abdalla Ahmed, Ori Scott, Elzbieta Hyatt, Paul Delgado-Olguin, Shagana Visuvanathan, Evgueni A Ivakine, Ronald D Cohn","doi":"10.1242/dmm.050595","DOIUrl":"10.1242/dmm.050595","url":null,"abstract":"<p><p>Becker muscular dystrophy (BMD) is a rare X-linked recessive neuromuscular disorder, frequently caused by in-frame deletions in the DMD gene that result in the production of a truncated, yet functional, dystrophin protein. The consequences of BMD-causing in-frame deletions on the organism are difficult to predict, especially in regard to long-term prognosis. Here, we used CRISPR-Cas9 to generate a new Dmd Δ52-55 mouse model by deleting exons 52-55 in the Dmd gene, resulting in a BMD-like in-frame deletion. To delineate the long-term effects of this deletion, we studied these mice over 52 weeks by performing histology and echocardiography analyses and assessing motor functions. Our results suggest that truncated dystrophin is sufficient to maintain wildtype-like muscle and heart histology and functions in young mice. However, the truncated protein appeared to be insufficient to maintain normal muscle homeostasis and protect against exercise-induced damage at 52 weeks. To further delineate the effects of this exon 52-55 in-frame deletion, we performed RNA sequencing pre- and post-exercise and identified several differentially expressed pathways that reflect the abnormal muscle phenotype observed at 52 weeks in the BMD model.</p>","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12519546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jack Barrington, Jack Rivers-Auty, Patrick Strangward, Sabrina Tamburrano, Nikolett Lénárt, Tessa Swanton, Eloise Lemarchand, Adrian R Parry-Jones, Ádám Dénes, David Brough, Stuart M Allan
{"title":"Interleukin-1 regulates myeloid cell trafficking and cerebral blood flow following intracerebral haemorrhage.","authors":"Jack Barrington, Jack Rivers-Auty, Patrick Strangward, Sabrina Tamburrano, Nikolett Lénárt, Tessa Swanton, Eloise Lemarchand, Adrian R Parry-Jones, Ádám Dénes, David Brough, Stuart M Allan","doi":"10.1242/dmm.052306","DOIUrl":"10.1242/dmm.052306","url":null,"abstract":"<p><p>Intracerebral haemorrhage (ICH) is a devastating stroke subtype lacking effective therapies. Understanding key pathological processes related to acute brain damage will help deliver better outcomes for ICH. Herein, we provide evidence that myeloid cell trafficking to the parenchyma is a conserved feature of ICH in clinical and experimental settings. Consistent with others, we show that monocytes contribute to acute brain damage following collagenase-induced murine ICH. Using RNA sequencing, we identified the pro-inflammatory cytokine interleukin-1 (IL-1) as a potential upstream regulator of the acute inflammatory response, with histological data pinpointing mononuclear phagocytes as the principal cellular source of IL-1 in patient and animal tissue. In agreement, inhibition of IL-1 receptor 1 (IL-1R1) with IL-1 receptor antagonist reduced recruitment of myeloid cells. However, IL-1R1 inhibition also worsened neuromotor outcomes and reduced cerebral blood flow to the affected hemisphere. Thus, we reveal dichotomous actions of IL-1-dependent inflammation following brain haemorrhage. Although IL-1 regulates myeloid cell trafficking, it also appears to regulate cerebral blood flow. Therefore, further investigation into the consequences of IL-1 signalling following brain haemorrhage is required to clarify future therapeutic options.</p>","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12519545/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Clare F Muir, Constantino Carlos Reyes-Aldasoro, Tomasz K Prajsnar, Bartosz J Michno, Justyna Cholewa-Waclaw, Yin X Ho, Audrey Bernut, Catherine A Loynes, Stone Elworthy, Kieran A Bowden, Ashley J Cadby, Lynne R Prince, Jason S King, Felix Ellett, Alison M Condliffe, Stephen A Renshaw
{"title":"Correction: A subset of neutrophil phagosomes is characterised by pulses of Class I PI3K activity.","authors":"Clare F Muir, Constantino Carlos Reyes-Aldasoro, Tomasz K Prajsnar, Bartosz J Michno, Justyna Cholewa-Waclaw, Yin X Ho, Audrey Bernut, Catherine A Loynes, Stone Elworthy, Kieran A Bowden, Ashley J Cadby, Lynne R Prince, Jason S King, Felix Ellett, Alison M Condliffe, Stephen A Renshaw","doi":"10.1242/dmm.052685","DOIUrl":"https://doi.org/10.1242/dmm.052685","url":null,"abstract":"","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":"18 10","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kara Braunreiter, Amber Kempton, Maria Katherine Mejia-Guerra, Andrew Murray, Stephen Baine, Kaitlin Adegboye, Alex Haile, Suruchi Jai Kumar Ahuja, Alessandra Fedoce, Chang Liu, Peter Burch, Ami Meda Kabadi
{"title":"Characterization of a humanized mouse model of Duchenne muscular dystrophy to support the development of genetic medicines.","authors":"Kara Braunreiter, Amber Kempton, Maria Katherine Mejia-Guerra, Andrew Murray, Stephen Baine, Kaitlin Adegboye, Alex Haile, Suruchi Jai Kumar Ahuja, Alessandra Fedoce, Chang Liu, Peter Burch, Ami Meda Kabadi","doi":"10.1242/dmm.052182","DOIUrl":"https://doi.org/10.1242/dmm.052182","url":null,"abstract":"<p><p>Duchenne muscular dystrophy (DMD) is a rare, progressive neuromuscular disease resulting from DMD variants, leading to loss of functional dystrophin. To evaluate human-targeted genetic medicines for functional dystrophin restoration, humanized genetic models containing the full human locus are required. This study characterized the hDMDΔ52/mdx mouse model previously reported by Pickar-Oliver and colleagues. Genomic characterization confirmed complete DMD duplication with identical exon 52 deletion junctions on both copies. Histological analysis showed increased diaphragm fibrosis and skeletal muscle central nuclei in hDMDΔ52/mdx mice versus hDMD/mdx controls. hDMDΔ52/mdx mice demonstrated reduced tibialis anterior specific force, decreased skeletal muscle fiber diameter, decreased resistance to eccentric contraction-induced damage and cardiac defects. Multiple serum biomarkers of disease were identified. Using a CRISPR/Cas9 gene-editing strategy to restore human functional dystrophin protein expression, detectable dystrophin expression in the heart and skeletal muscle and increased resistance to injury in the tibialis anterior muscle were observed. In summary, hDMDΔ52/mdx mice display multiple physiological and functional deficits associated with DMD pathology, which can be restored by human-targeted therapy, confirming the suitability of this model for developing human-targeted genetic medicines.</p>","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":"18 10","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145307220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Max Gijsbertsen, Irene M J Mathijssen, Ana F Duarte Madancos, Johannes P T M van Leeuwen, Jeroen van de Peppel
{"title":"Generation of human induced pluripotent stem cell lines from patients with FGFR2-linked syndromic craniosynostosis.","authors":"Max Gijsbertsen, Irene M J Mathijssen, Ana F Duarte Madancos, Johannes P T M van Leeuwen, Jeroen van de Peppel","doi":"10.1242/dmm.052123","DOIUrl":"10.1242/dmm.052123","url":null,"abstract":"<p><p>Craniosynostosis is a multigenic congenital condition in which one or more calvarial sutures have prematurely fused during the development of the fetus. Pathogenic variants in FGFR2 are associated with the development of syndromic craniosynostosis, such as Crouzon, Apert and Pfeifer syndromes. Investigation of FGFR2-linked craniosynostosis is hindered by the lack of appropriate in vitro models. Patient-derived human induced pluripotent stem cell (hiPSC) in vitro disease models provide the opportunity to investigate the disease, identify molecular targets for pharmaceutical treatments, and enable the generation of autologous pluripotent stem cell catalogues. Here, we report three patient-derived hiPSC lines carrying the C342Y, S252W or E565G FGFR2 pathogenic variant. The patient hiPSC lines express characteristic pluripotency markers and display distinct phosphorylation profiles under unstimulated conditions. FGFR2C342Y showed autophosphorylation in the absence of bFGF ligand, although downstream docking proteins PLCγ and FRS2α were not phosphorylated. FGFR2S252W and FGFR2E565G hiPSCs showed increased phosphorylation of docking proteins PLCγ and FRS2α, whereas FGFR2 was not phosphorylated. These patient hiPSC lines provide molecular and cellular options to investigate FGFR2-linked craniosynostosis in the patient-specific genomic context and develop therapeutic modalities.</p>","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12486208/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Johann G Maass, Dominik Kamionek, Annabelle Mantilleri, Susanne Theiss, Laura Dötsch, Felix Franke, Tim Schubert, Jonas G Scheck, Claudia Pitzer, Paolo Piovani, Michele Bertacchi, Olivier Deschaux, Anubhav Singh, Chun-An Chen, Henning Fröhlich, Michèle Studer, Christian P Schaaf
{"title":"Models of Bosch-Boonstra-Schaaf optic atrophy syndrome reveal genotype-phenotype correlations in brain structure and behavior.","authors":"Johann G Maass, Dominik Kamionek, Annabelle Mantilleri, Susanne Theiss, Laura Dötsch, Felix Franke, Tim Schubert, Jonas G Scheck, Claudia Pitzer, Paolo Piovani, Michele Bertacchi, Olivier Deschaux, Anubhav Singh, Chun-An Chen, Henning Fröhlich, Michèle Studer, Christian P Schaaf","doi":"10.1242/dmm.052426","DOIUrl":"10.1242/dmm.052426","url":null,"abstract":"<p><p>Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS) is a rare, autosomal dominant neurodevelopmental disorder caused by pathogenic variants in NR2F1, characterized by developmental delay, intellectual disability, optic nerve anomalies and autism spectrum disorder. Most pathogenic variants cluster within the highly conserved DNA-binding domain (DBD) or ligand-binding domain (LBD) of NR2F1 and are associated with variable clinical severity, suggesting a genotype-phenotype correlation. Although previous mouse models have provided important insights, comprehensive behavioral characterization remains limited. Here, we present two novel BBSOAS mouse models harboring patient-specific variants in the DBD (Nr2f1+/R139L) and LBD (Nr2f1+/E397*), alongside the established Nr2f1+/- model. We analyzed brain morphology and behavior to further expand the murine phenotype and investigate the genotype-phenotype correlation. We demonstrate that these models recapitulate key aspects of the BBSOAS phenotype, including deficits in cognition, social communication and motor function, and that the presence and severity of behavioral abnormalities are dependent on variant type. Our findings provide new evidence for a genotype-phenotype correlation associated with domain-specific NR2F1 variants and establish a robust platform for future mechanistic and therapeutic studies.</p>","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12505268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Robin A Karge, Florian P Fischer, Hannah Schüth, Aileen Wechner, Sabrina Peter, Lukas Kilo, Mato Dichter, Aaron Voigt, Gaia Tavosanis, Karen M J van Loo, Henner Koch, Yvonne G Weber, Stefan Wolking
{"title":"Modeling AP2M1 developmental and epileptic encephalopathy in drosophila.","authors":"Robin A Karge, Florian P Fischer, Hannah Schüth, Aileen Wechner, Sabrina Peter, Lukas Kilo, Mato Dichter, Aaron Voigt, Gaia Tavosanis, Karen M J van Loo, Henner Koch, Yvonne G Weber, Stefan Wolking","doi":"10.1242/dmm.052419","DOIUrl":"https://doi.org/10.1242/dmm.052419","url":null,"abstract":"<p><p>Genetic defects in AP2M1, which encodes the μ-subunit of the adaptor protein complex 2 (AP-2) essential for clathrin-mediated endocytosis (CME), cause a rare form of developmental and epileptic encephalopathy (DEE). In this study, we modeled AP2M1-DEE in Drosophila melanogaster to gain deeper insights into the underlying disease mechanisms. Pan-neuronal RNA interference (RNAi) against the Drosophila AP2M1 ortholog, AP-2µ, resulted in a consistent heat-sensitive paralysis phenotype and altered morphology in class IV dendritic arborization (c4da) neurons. Unexpectedly, affected flies were resistant to antiseizure medications and exhibited decreased susceptibility to electrically induced seizures. A CRISPR-engineered fly line carrying the recurrent human disease variant p.Arg170Trp displayed a milder seizure resistant phenotype. While these findings contrast with the human phenotype, they align with previous studies on other CME-related genes in Drosophila. Our results suggest that hyperexcitability and seizures in AP2M1-DEE may stem from broader defects in neuronal development rather than direct synaptic dysfunction.</p>","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Noncoding and coding mechanisms of aging heart failure with preserved ejection fraction with thyroid dysfunction.","authors":"Sankalpa Chakraborty, Olivia Sloan, Bryce Dickerson, Gourav Chakraborty, Shuang Li, Curren Bounds, Sophia Lemus, Caleb Hickman, J Mauro Calabrese, Viswanathan Rajagopalan","doi":"10.1242/dmm.052207","DOIUrl":"https://doi.org/10.1242/dmm.052207","url":null,"abstract":"<p><p>Heart Failure with preserved Ejection Fraction (HFpEF) is a lethal, heterogeneous, geriatric syndrome. Long noncoding RNAs (lncRNAs) constitute the majority of the functional mammalian transcriptome and are key regulators in complex pathophysiology. However, the roles of lncRNAs in aging HFpEF associated with thyroid hormone (TH) dysfunction are unclear. We investigated the well-established ZSF1 model in early and severe, aged HFpEF (5-, 13-, and 20-months [mo]). Both serum THs significantly decreased in HFpEF in a temporal manner. Echocardiogram showed preserved cardiac function. Morphometric and histologic analyses showed significant cardiac hypertrophy in HFpEF. LncRNA microarray and RT-qPCR revealed that three lncRNAs were significantly increased predominantly in 13-mo HFpEF. LncRNA knockdown showed improvement in cell viability, which was further enhanced with T3 (active TH). Microarray analyses showed that two mRNAs were significantly altered in early HFpEF. We also identified previously unreported tissue and serum inflammatory cytokine markers in early and late HFpEF. Taken together, we have shown novel noncoding and coding markers in early and/or late-aged hypothyroid HFpEF. Further studies may develop translatable diagnostic and therapeutic targets for HFpEF.</p>","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Roza H A Masalmeh, John C Dawson, Virginia Alvarez Garcia, Morwenna T Muir, Roderick N Carter, Giles Hardingham, Cameron Davies, Rosina Graham, Alex von Kriegsheim, Jair Marques, Chinmayi Pednekar, Steven M Pollard, Neil O Carragher, Valerie G Brunton, Margaret C Frame
{"title":"FAK modulates glioblastoma stem cell energetics via regulation of glycolysis and glutamine oxidation.","authors":"Roza H A Masalmeh, John C Dawson, Virginia Alvarez Garcia, Morwenna T Muir, Roderick N Carter, Giles Hardingham, Cameron Davies, Rosina Graham, Alex von Kriegsheim, Jair Marques, Chinmayi Pednekar, Steven M Pollard, Neil O Carragher, Valerie G Brunton, Margaret C Frame","doi":"10.1242/dmm.052634","DOIUrl":"https://doi.org/10.1242/dmm.052634","url":null,"abstract":"<p><p>Glycolysis and the TCA cycle are reprogrammed in cancer cells to meet bioenergetic and biosynthetic demands, including by engagement with the extracellular matrix (ECM). However, the mechanisms by which the ECM engagement reprograms core energy metabolism is still un known. We show that the canonical cell-ECM adhesion protein FAK, and specifically its kinase activity, is driving cellular energetics. Using a stem cell model of glioblastoma, we show that FAK gene deletion simultaneously inhibits glycolysis and glutamine oxidation, increases mitochondrial fragmentation, elevates phosphorylation of the mitochondrial protein MTFR1L at S235 and triggers a mesenchymal-to-epithelial transition. These metabolic and structural changes arise through altered acto-myosin contractility as shown by phospho-myosin light chain (p-MLC S19). This can be reversed by Rho-kinase (ROCK) inhibitors revealing mechanotransduction pathway control of both mitochondrial dynamics and glutamine oxidation. FAK-dependent metabolic programming is associated with regulation of cell migration, invasive capacity and tumour growth in vivo. Our work describes a previously unrecognised FAK-ROCK axis that couples mechanical cues to the rewiring of energy metabolism, linking cell shape, mitochondrial function, and malignant behaviour.</p>","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145112171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Paula Schuster-Winkelmann, Veronika Weß, Marietta Schindler, Morten Ø Jensen, David E Shaw, Paolo Alberton, Hendrik Schulze-Koops, Silvia Schoenthaler, Andreas Weinhaeusel, Matthias Siebeck, Roswitha Gropp, Attila Aszodi
{"title":"Validation of a rheumatoid arthritis mouse model that uses NOD-scid IL2Rγnull mice reconstituted with patient PBMCs.","authors":"Paula Schuster-Winkelmann, Veronika Weß, Marietta Schindler, Morten Ø Jensen, David E Shaw, Paolo Alberton, Hendrik Schulze-Koops, Silvia Schoenthaler, Andreas Weinhaeusel, Matthias Siebeck, Roswitha Gropp, Attila Aszodi","doi":"10.1242/dmm.052294","DOIUrl":"https://doi.org/10.1242/dmm.052294","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation and joint destruction. Replicating human manifestations of RA in animal models remains challenging, however, due to heterogeneity of the disease. In this study, a humanized mouse model for RA was developed and validated using NOD-scid IL2Rnull (NSG) mice engrafted with peripheral blood mononuclear cells (PBMCs) from RA patients (NSG-RA). RA symptoms were induced using lipopolysaccharide and a cocktail of antibodies against type II collagen. Pathological manifestations were assessed through clinical scoring of hind paw swelling, histological analysis, and evaluation of RA-specific markers in plasma and joints using Luminex, RT-PCR, and RNA-seq. NSG-RA mice exhibited increased levels of RA-specific markers, an influx of inflammatory cells into the synovium, bone erosion, and elevated levels of human autoantibodies. Enriched RNA-seq pathway analysis revealed activation of the RA disease pathway, along with the TNF and IL-17 signaling pathways. Treatment with prednisolone or infliximab ameliorated disease symptoms and decreased levels of inflammatory markers. These findings indicate that the NSG-RA model offers a translational tool for studying RA pathogenesis and testing novel therapeutic approaches.</p>","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145112155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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