X-linked Adrenoleukodystrophy (X-ALD) Animal Model Service

The Abcd1-KO mouse model is a genetically engineered platform that recapitulates the biochemical hallmarks of X-linked adrenoleukodystrophy (X-ALD) through targeted disruption of the ABCD1 transporter gene. Protheragen provides the rigorously validated Abcd1-KO mouse model, characterized by comprehensive phenotypic and biochemical profiling, to deliver highly reliable preclinical data for X-ALD therapeutic development and mechanism studies.

Introduction to X-linked Adrenoleukodystrophy (X-ALD) Animal Models

Animal models of X-linked adrenoleukodystrophy (X-ALD), primarily the Abcd1 knockout mouse, serve as essential tools for investigating the pathophysiology and therapeutic development for this neurodegenerative disorder. These models recapitulate key biochemical hallmarks of the human disease, notably the accumulation of very long-chain fatty acids (VLCFAs) in tissues and associated oxidative stress and neuroinflammation. The establishment of animal models for X-ALD is crucial for evaluating therapeutic strategies, providing critical insights into disease mechanisms and treatment efficacy.

Fig.1 Development of a rabbit model for adrenoleukodystrophy (ALD): A pilot study on gene therapy using rAAV9. (Zhou X, et al., 2025)

Our Services

As a leader in rare neurometabolic disease research, Protheragen offers comprehensive and highly specialized animal model development services for X-linked adrenoleukodystrophy (X-ALD). Our expertise in genetic engineering and phenotyping enables us to provide reliable, well-characterized, and customizable models that accurately recapitulate the complex pathophysiology of X-ALD, providing valuable tools for client's mechanistic studies and preclinical efficacy testing.

Animal Models of X-linked Adrenoleukodystrophy (X-ALD)

Case Study-Human ABCD1-p.G512S (c.1534G>A) KI Mouse Model

Model Introduction

X-linked adrenoleukodystrophy (X-ALD) is a progressive neurodegenerative disorder caused by mutations in the ABCD1 gene, leading to impaired peroxisomal beta-oxidation and accumulation of very long-chain fatty acids. To establish a clinically relevant platform for studying disease mechanisms and evaluating therapies, we developed a humanized knock-in mouse model carrying the patient-derived ABCD1-p.G512S (c.1534G>A) mutation, designated as the hALD mouse.

Methodology

• Animal Model: Human ABCD1-p.G512S knock-in (hALD) mice and wild-type (WT) controls on a C57BL/6N background.
• Modeling Method: The mouse model was generated by using gene editing to knock-in (KI) human cDNA carrying the patient-derived ABCD1-p.G512S (c.1534G>A) mutation into mouse fertilized embryos, followed by embryo transfer and breeding of positive founders to establish a stable KI line.
• Validation Methods:
  • Genotypic confirmation by DNA sequencing.
  • qRT-PCR analysis of human ABCD1 mRNA expression in brain and testis tissues.

Phenotypic Analysis & Results

Molecular analysis confirmed successful expression of the mutant human transgene in clinically relevant tissues.

• Mutant Gene Expression: qRT-PCR analysis demonstrated significantly elevated expression of mutant human ABCD1 mRNA in both brain and testis of hALD mice compared to WT controls (Fig.2).
• Tissue-Specific Expression Pattern: The robust expression in these two clinically affected organs confirms the model's relevance for studying X-ALD pathology.

Fig.2 Expression of the human ABCD1 gene in the brain and testis of WT and hALD mice. (A) mRNA levels in brain tissue. (B) mRNA levels in testis tissue. Data are presented as mean ± SEM (n=2/genotype; *p < 0.05 vs. WT).

Conclusion

This case study validates the human ABCD1-p.G512S knock-in mouse as a molecularly characterized model for X-linked adrenoleukodystrophy (X-ALD) research. The demonstrated expression of mutant human ABCD1 mRNA in key affected tissues provides a genetically accurate platform for investigating ALD disease mechanisms and evaluating therapeutic interventions targeting ABCD1 dysfunction.

Contact Us

Leveraging precise animal models, Protheragen is dedicated to providing a comprehensive suite of preclinical research services for X-linked adrenoleukodystrophy (X-ALD). Our services include pharmacodynamics (PD), pharmacokinetics (PK), and toxicology studies, all designed to support the development and regulatory approval of potential therapies. 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. Zhou X, Ma C Y, Zhang X, et al. Development of a rabbit model for adrenoleukodystrophy: A pilot study on gene therapy using rAAV9[J]. Molecular Therapy Nucleic Acids, 2025, 36(1).