Wilson's Disease Animal Model Service

Wilson's disease animal models, particularly the Atp7b^-/- mouse and LEC rat, are indispensable for elucidating copper homeostasis mechanisms, evaluating the efficacy of chelation therapy, and developing novel gene-based treatments for this metabolic disorder. At Protheragen, we are committed to advancing the understanding and management of Wilson's disease through cutting-edge disease modeling services.

Overview of Wilson's Disease Animal Models

Animal models of Wilson's disease, primarily rodents with targeted disruptions in the Atp7b gene, serve as essential tools for investigating disease pathogenesis and therapeutic development. The most widely used model is the Atp7b knockout mouse, which recapitulates key features of the human condition including hepatic copper accumulation, liver pathology (steatosis, necrosis), and eventual neurological manifestations. Additional models such as the Long-Evans Cinnamon (LEC) rat, which possesses a natural Atp7b mutation, provide complementary insights through spontaneous disease progression.

Fig.1 Evaluation of efficacy and safety of AAV8-ΔC4ATP7B gene therapy in a mutant mouse model of Wilson's disease. (Zeng C, et al., 2025)

Our Services

Protheragen provides comprehensive animal model development services to accelerate groundbreaking research in Wilson's disease. We specialize in creating and validating a diverse portfolio of genetically engineered models that accurately recapitulate the genetic and metabolic hallmarks of the human disease. Our expertise spans multiple species and cutting-edge technologies, enabling us to deliver tailored solutions for every stage of your investigative pipeline.

Animal Models of Wilson's Disease

Featured Animal Models

Case Study-Atp7b^KI/KI Mouse Model

Model Introduction

Wilson's disease is an inherited disorder of copper metabolism caused by mutations in the ATP7B gene, leading to pathological copper accumulation in the liver and other tissues. To establish a genetically precise platform for investigating copper homeostasis disruption and evaluating potential therapies, we developed a knock-in mouse model carrying the pathogenic c.2339G>T (p.R780L) mutation in the Atp7b gene, designated as the Atp7b^KI/KI mouse.

Methodology

• Animal Model: Atp7b^KI/KI homozygous mice and wild-type (Atp7b^+/+) controls on a C57BL/6 background.
• Modeling Method: Using gene editing technology, the c.2339G>T (p.R780L) mutation in the Atp7b gene was introduced into C57BL/6 mice, generating heterozygous knock-in (KI) mice (Atp7b^KI/+). These heterozygous mice were then interbred to generate homozygous KI mice (Atp7b^KI/KI) and wild-type mice (Atp7b^+/+).
• Phenotypic Analysis: Key parameters of copper metabolism were assessed, including:
  • Ceruloplasmin activity: A diagnostic indicator reflecting functional copper utilization.
  • Hepatic copper content: Direct measurement of pathological copper accumulation.
  • Urinary copper excretion: Biomarker of systemic copper overload status.

Phenotypic Analysis & Results

Metabolic analysis confirmed that Atp7b^KI/KI mice recapitulate the characteristic copper homeostasis disruption of human Wilson's disease.

• Impaired Copper Metabolism: Atp7b^KI/KI mice exhibited significantly reduced ceruloplasmin activity compared to wild-type controls, confirming defective copper incorporation and transport (Fig.2A).
• Hepatic Copper Accumulation: Excessive copper accumulation was observed in the liver of Atp7b^KI/KI mice, consistent with the hepatic pathology of Wilson's disease (Fig.2B).
• Increased Copper Excretion: Urinary copper excretion in Atp7b^KI/KI mice was also significantly higher than that in age-matched Atp7b^+/+ mice (Fig.2C).

Fig.2 Copper metabolism profile in Atp7b^KI/KI mice. (A) Ceruloplasmin activity levels. (B) Hepatic copper content. (C) Urinary copper excretion. Data are presented as mean ± SEM (n=6-8). *p < 0.05, **p < 0.01 vs. wild-type.

Conclusion

This case study validates the Atp7b^KI/KI mouse as a highly relevant model for Wilson's disease research. The model demonstrates the hallmark features of copper metabolism dysregulation, including hepatic copper accumulation and altered copper excretion. This genetically precise knock-in model provides a valuable platform for investigating disease mechanisms and evaluating novel therapeutic strategies for Wilson's disease.

Contact Us

At Protheragen, we are committed to developing comprehensive Wilson's disease animal models to advance therapeutic development through integrated pharmacodynamics (PD), pharmacokinetics (PK), and toxicology studies. Our validated models serve as critical tools for evaluating drug efficacy, metabolic stability, and safety profiles, providing robust preclinical data to support regulatory submissions. If you are interested in our animal model development services, please do not hesitate to contact us for more details and quotation information.

Reference

1. Zeng C, Lin Y, Lu X, et al. Evaluation of efficacy and safety of AAV8-ΔC4ATP7B gene therapy in a mutant mouse model of Wilson's disease[J]. Molecular Therapy Methods & Clinical Development, 2025, 33(1).