Wilson Disease Animal Model Service
Animal models for Wilson disease facilitate the study of disease mechanisms, regulation of copper metabolism, and the safe and effective evaluation of potential therapeutics. Protheragen provides comprehensive and highly specialized animal model development services to accelerate therapeutic breakthroughs for Wilson disease. We provide fully integrated services to assist in the preclinical phase of research, from the development and validation of the model to bespoke in vivo studies, thereby supplying the client with the necessary models that are solid, trustworthy, and pertinent for assessing new therapeutics.
Overview of Wilson Disease Animal Models
Wilson disease is an autosomal recessive disorder of copper transport caused by mutations in the ATP7B gene, leading to toxic copper accumulation primarily in the liver and brain. Unraveling this disease complex pathophysiology and assessing new therapeutic approaches, ranging from small molecules and gene therapy to cell-based therapies, requires a strong and predictive animal model. Animal models recapitulate key aspects of the human condition, including hepatic copper accumulation, liver pathology, and in some cases, neurological manifestations. These models serve as a critical bridge between in vitro findings and human trials, providing invaluable data on drug efficacy, mechanism of action, and biodistribution.
Fig.1 LEC ameliorates liver injury and restores lipid metabolism in Atp7b-/- mice. (Ho, W. I., et al., 2022)Our Services
Protheragen offer end-to-end support for your Wilson disease research, including model selection, custom generation of genetically engineered models, phenotypic characterization, and tailored preclinical trial design. Our team manages all aspects of in vivo study execution, from dosing and monitoring to tissue collection and biomarker analysis, delivering robust, reliable data tailored to your drug development pipeline.
Animal Models of Wilson Disease
Protheragen utilizes advanced technologies to create tailored models with high precision to accelerate your Wilson disease research. Each model is validated through extensive phenotypic, biochemical, and histological analyses to confirm copper accumulation and functional deficits.
Optional models:
- Atp7b knockout model
- Atp7b mutation model
- Others
Mouse Model for Wilson Disease Research
| Model Name | Modeling Method | Sales Status | Detailed Description |
|---|---|---|---|
| Atp7b-KO Mouse Model | Knockout | Sperm Cryopreservation | This model features a targeted deletion of exon 2 in the Atp7b gene, achieved through gene editing technology. |
| Atp7b-KO (2) Mouse Model | Knockout | Sperm Cryopreservation | This model carries an extensive genomic deletion spanning exons 2 to 20 of the Atp7b gene. |
| hATP7B Mouse Model | Knock-in | Repository Live | This humanized model is designed to express the human ATP7B protein in place of the murine equivalent. |
| hATP7B*H1069Q Mouse Model | Point Mutation | Repository Live | This model carries the classic human pathogenic mutation H1069Q within the context of the humanized ATP7B gene. |
Case Study-Atp7b KO Mouse Model Development
Model Introduction
The Atp7b knockout (Atp7b KO) mouse model serves as a robust and well-characterized preclinical tool for investigating Wilson disease pathogenesis and evaluating therapeutic interventions. This model is characterized by the loss of functional ATP7B protein, a pivotal hepatic copper-transporting ATPase. This loss leads to a progressive failure of biliary copper excretion, thereby mirroring the biochemical defect observed in human individuals. As a result, the model reliably recapitulates the hallmark features of systemic copper accumulation, making it ideal for studying disease progression and therapy efficacy.
Methodology
- Animal Model: The Atp7b KO mouse model was generated on a C57BL/6 background via advanced genetic engineering techniques. The targeting strategy involved the deletion of a genomic segment spanning exons 2 to 20, thereby ensuring the abolishment of functional ATP7B protein.
- Phenotypic Analysis Methods: A comprehensive phenotypic characterization was performed to validate the model. Hepatic Atp7b mRNA expression levels were quantified using RT-qPCR. Protein expression of ATP7B in liver tissue was assessed by western blot analysis. Key serum biomarkers of hepatic function, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP), were measured. Additionally, renal function was evaluated by measuring serum creatinine (CREA-S) and uric acid levels.
Phenotypic Analysis & Results
A near-total absence of Atp7b mRNA expression was confirmed in the livers of Atp7b KO mice via RT-qPCR compared to wild-type (WT) controls. Western blot analysis further demonstrated the complete lack of ATP7B protein expression in the knockout animals. Biochemically, Atp7b KO mice exhibited markedly elevated serum levels of liver enzymes (ALT, AST, ALP), indicating substantial hepatocellular damage and cholestatic stress. Additionally, significant increases in renal biomarkers (creatinine and uric acid) were detected, pointing to concomitant renal metabolic abnormalities.
Fig.2 Validation of the Atp7b KO Mouse Model. (A) Hepatic Atp7b mRNA expression levels were nearly abolished in Atp7b KO mice compared to WT controls. (B) Serum levels of liver enzymes (ALT, AST, ALP) were significantly elevated in Atp7b KO mice. (C) Atp7b KO mice exhibited significant increases in renal function markers (CREA-S, uric acid). Data are presented as mean ± SEM (n=6; **p < 0.01, *p < 0.05).Conclusion
The comprehensive dataset from the Atp7b KO mouse model collectively demonstrates its high pathophysiological relevance to human Wilson disease. The strong correlation with the human disease profile establishes this model as a valuable and predictive system, ideally suited for investigating disease mechanisms, screening novel copper-chelating agents, and evaluating advanced therapeutic modalities such as gene therapy.
Contact Us
Protheragen's expertise in rare disease models, combined with deep knowledge of copper metabolism and disease pathologies, enables us to deliver physiologically relevant, well-validated animal models that meet stringent regulatory standards. Our end-to-end support includes model generation, comprehensive phenotypic validation, therapeutic efficacy studies, and critical pharmacokinetics and drug safety evaluation services. We ensure rapid turnaround, high reproducibility, and full study support, from design to data delivery. If you are interested in our services, please feel free to contact us.
Reference
- Ho, Wai-In et al. "Liposome-encapsulated curcumin attenuates HMGB1-mediated hepatic inflammation and fibrosis in a murine model of Wilson's disease." Biomedicine & pharmacotherapy 152 (2022): 113197.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.