DOI: 10.1002/ame2.12564
Refining the adriamycin-induced focal segmental glomerulosclerosis mouse model to improve reproducibility and animal welfare
Haochen Jiang1
Salma Althobaiti1
Braeden Pinkerton1
Xin Fu1
Zhenshan Jia1
Kirk W.Foster2
Geoffrey M.Thiele3
Troy J.Plumb4
Dong Wang1
1.Department of Pharmaceutical Sciences,College of Pharmacy,University of Nebraska Medical Center,Omaha,Nebraska,USA2.Department of Pathology and Microbiology,College of Medicine,University of Nebraska Medical Center,Omaha,Nebraska,USA3.Division of Rheumatology and Immunology,Department of Internal Medicine,College of Medicine,University of Nebraska Medical Center,Omaha,Nebraska,USA;Veterans Affairs(VA) Nebraska-Western Iowa Health Care System,Omaha,Nebraska,USA4.Division of Nephrology,Department of Internal Medicine,College of Medicine,University of Nebraska Medical Center,Omaha,Nebraska,USA
摘要：Background:Reliable animal models are crucial to drug development for focal seg-mental glomerulosclerosis(FSGS),a rare kidney disease.Variability in success rates in literature and significant ethical concerns with animal welfare necessitate further optimization of adriamycin(ADR)-induced FSGS model developed on BALB/c mice.
Methods:High-performance liquid chromatography(HPLC)was used to assess ADR stability in water and upon light exposure.To identify the optimal ADR level,sin-gle intravenous ADR injections with dosing levels from 10 to 17mg/kg body weight were administered to BALB/c mice to induce FSGS-like pathology.Body weight and proteinuria of FSGS mice were monitored and analyzed for FSGS model-associated morbidity.Animals were euthanized for hematological and kidney histological assess-ments 8weeks post induction.To identify the suitable experiment time frame of the ADR-induced FSGS mouse model,a longitudinal study was performed,with an 11-week continuous monitoring of the symptoms.
Results:ADR was found to be unstable in aqueous media and light sensitive.A dosing level of 10.5 mg/kg of ADR was optimal for consistent FSGS mouse model induction on BALB/c strain,characterized by minimal mortality and sustained FSGS-like symp-toms.Findings from the longitudinal study suggest that 6weeks post ADR induction may represent the peak of FSGS pathology severity in this mouse model.This time frame may be used for FSGS drug development projects.
Conclusion:Based on the outcome from this study,we identified the optimal ADR dosing level and model testing duration.A standard operating procedure(SOP)for the ADR-induced FSGS mouse model was established to facilitate FSGS basic research and drug development.
机标关键词：improvemousemodeladriamycinanimalfocalinducedrefining
论文发表日期：2025-03-01
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：10( 854-863 )
英文信息