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":null,"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":3.3000,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Disease Models & Mechanisms","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1242/dmm.052294","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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.
期刊介绍:
Disease Models & Mechanisms (DMM) is an online Open Access journal focusing on the use of model systems to better understand, diagnose and treat human disease.