Refining the adriamycin‐induced focal segmental glomerulosclerosis mouse model to improve reproducibility and animal welfare
Abstract Background Reliable animal models are crucial to drug development for focal segmental 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)–induce...
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Wiley
2025-05-01
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| Series: | Animal Models and Experimental Medicine |
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| Online Access: | https://doi.org/10.1002/ame2.12564 |
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| author | Haochen Jiang Salma Althobaiti Braeden Pinkerton Xin Fu Zhenshan Jia Kirk W. Foster Geoffrey M. Thiele Troy J. Plumb Dong Wang |
| author_facet | Haochen Jiang Salma Althobaiti Braeden Pinkerton Xin Fu Zhenshan Jia Kirk W. Foster Geoffrey M. Thiele Troy J. Plumb Dong Wang |
| author_sort | Haochen Jiang |
| collection | DOAJ |
| description | Abstract Background Reliable animal models are crucial to drug development for focal segmental 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, single intravenous ADR injections with dosing levels from 10 to 17 mg/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 assessments 8 weeks 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 symptoms. Findings from the longitudinal study suggest that 6 weeks 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. |
| format | Article |
| id | doaj-art-6499cc5e4b0842fc8833dc0e838d76f8 |
| institution | DOAJ |
| issn | 2576-2095 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Wiley |
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| series | Animal Models and Experimental Medicine |
| spelling | doaj-art-6499cc5e4b0842fc8833dc0e838d76f82025-08-20T03:12:31ZengWileyAnimal Models and Experimental Medicine2576-20952025-05-018585486310.1002/ame2.12564Refining the adriamycin‐induced focal segmental glomerulosclerosis mouse model to improve reproducibility and animal welfareHaochen Jiang0Salma Althobaiti1Braeden Pinkerton2Xin Fu3Zhenshan Jia4Kirk W. Foster5Geoffrey M. Thiele6Troy J. Plumb7Dong Wang8Department of Pharmaceutical Sciences, College of Pharmacy University of Nebraska Medical Center Omaha Nebraska USADepartment of Pharmaceutical Sciences, College of Pharmacy University of Nebraska Medical Center Omaha Nebraska USADepartment of Pharmaceutical Sciences, College of Pharmacy University of Nebraska Medical Center Omaha Nebraska USADepartment of Pharmaceutical Sciences, College of Pharmacy University of Nebraska Medical Center Omaha Nebraska USADepartment of Pharmaceutical Sciences, College of Pharmacy University of Nebraska Medical Center Omaha Nebraska USADepartment of Pathology and Microbiology, College of Medicine University of Nebraska Medical Center Omaha Nebraska USADivision of Rheumatology and Immunology, Department of Internal Medicine, College of Medicine University of Nebraska Medical Center Omaha Nebraska USADivision of Nephrology, Department of Internal Medicine, College of Medicine University of Nebraska Medical Center Omaha Nebraska USADepartment of Pharmaceutical Sciences, College of Pharmacy University of Nebraska Medical Center Omaha Nebraska USAAbstract Background Reliable animal models are crucial to drug development for focal segmental 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, single intravenous ADR injections with dosing levels from 10 to 17 mg/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 assessments 8 weeks 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 symptoms. Findings from the longitudinal study suggest that 6 weeks 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.https://doi.org/10.1002/ame2.12564adriamycin (ADR)focal segmental glomerulosclerosis (FSGS)instabilitykidneystandard operating procedure (SOP) |
| spellingShingle | Haochen Jiang Salma Althobaiti Braeden Pinkerton Xin Fu Zhenshan Jia Kirk W. Foster Geoffrey M. Thiele Troy J. Plumb Dong Wang Refining the adriamycin‐induced focal segmental glomerulosclerosis mouse model to improve reproducibility and animal welfare Animal Models and Experimental Medicine adriamycin (ADR) focal segmental glomerulosclerosis (FSGS) instability kidney standard operating procedure (SOP) |
| title | Refining the adriamycin‐induced focal segmental glomerulosclerosis mouse model to improve reproducibility and animal welfare |
| title_full | Refining the adriamycin‐induced focal segmental glomerulosclerosis mouse model to improve reproducibility and animal welfare |
| title_fullStr | Refining the adriamycin‐induced focal segmental glomerulosclerosis mouse model to improve reproducibility and animal welfare |
| title_full_unstemmed | Refining the adriamycin‐induced focal segmental glomerulosclerosis mouse model to improve reproducibility and animal welfare |
| title_short | Refining the adriamycin‐induced focal segmental glomerulosclerosis mouse model to improve reproducibility and animal welfare |
| title_sort | refining the adriamycin induced focal segmental glomerulosclerosis mouse model to improve reproducibility and animal welfare |
| topic | adriamycin (ADR) focal segmental glomerulosclerosis (FSGS) instability kidney standard operating procedure (SOP) |
| url | https://doi.org/10.1002/ame2.12564 |
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