Fabry Disease Animal Model Service
Fabry disease animal models serve as essential preclinical tools, reproducing the hallmark glycosphingolipid accumulation to evaluate the efficacy and safety of potential new therapies. At Protheragen, we pioneer the development of highly precise Fabry disease animal models to critically accelerate preclinical therapeutic discovery. Our expertise delivers gold-standard, biologically relevant models that provide our clients with the reliable research data.
Overview of Fabry Disease Animal Models
Animal models of Fabry disease, including knockout models completely lacking α-galactosidase A activity and knock-in models carrying specific human pathogenic mutations, successfully replicate the core biochemical hallmark of the disease, namely, the systemic accumulation of globotriaosylceramide (Gb3). Furthermore, they exhibit key pathological features in major target organs such as the kidneys, heart, and nervous system, providing a validated and reproducible platform for evaluating the efficacy of novel investigational therapies, including enzyme replacement therapy, substrate reduction therapy, and gene therapy, ultimately bridging the gap between basic research and clinical application.
Fig.1 ASIC1a-associated mechanical hypersensitivity in the GlaKO Fabry disease mouse model. (Montes M M, et al., 2025)
Challenges in Fabry Disease Animal Model Development
While animal models are essential for Fabry disease research, creating models that accurately recapitulate the human condition is fraught with difficulties. The primary challenges stem from fundamental biological differences between species and the complex nature of the disease itself.
- Incomplete Phenotype Recapitulation: While models successfully exhibit the core biochemical hallmark of Gb3 accumulation, they frequently fail to develop the severe end-organ damage (such as progressive renal failure or significant cardiovascular complications) that characterizes the human disease, limiting their predictive value.
- Species-Specific Differences: Fundamental physiological differences in glycosphingolipid metabolism and pathology between species mean that the pattern and consequences of Gb3 storage observed in animal models do not perfectly mirror the human disease process.
- Genetic and Phenotypic Variability: The wide clinical spectrum of human Fabry disease, driven by specific mutation types and genetic background, is difficult to capture. This necessitates the development of multiple, specific models to represent this diversity adequately.
Our Services
Protheragen empowers researchers in rare neurometabolic diseases with highly accurate, customizable animal models. Our Fabry disease models are rigorously validated to faithfully recapitulate human pathology, bridging the gap between basic research and clinical application. We provide the critical preclinical tools you need to reliably study mechanisms and evaluate novel therapies .
Animal Models of Fabry Disease
| Model Name | Model Type | Sales Status | Detailed Description |
| GlaKO Mice | GEMMs | Repository live | The GlaKO (Gla Knockout) mouse is a foundational model generated by the deletion of exons 2-3 of the endogenous Gla gene, resulting in a complete lack of α-galactosidase A activity. This model robustly recapitulates the core biochemical hallmark of Fabry disease: the systemic accumulation of globotriaosylceramide (Gb3). While these mice exhibit significant glycolipid storage, they typically do not develop the severe symptomatic phenotype, such as progressive organ failure, seen in human patients. |
| TgG3S/GlaKO Mice | GEMMs | Embryo cryopreservation | The TgG3S/GlaKO mouse represents a more advanced and clinically valuable model. This model is derived from a cross between basal GlaKO mice and transgenic mice expressing human Gb3 synthase (TgG3S). This model not only exhibits elevated total Gb3 levels but also displays a distinct symptomatic phenotype, including progressive renal impairment, making it a valuable tool for understanding disease progression and testing new therapies. |
Case Study-Gla Knockout (KO) Mouse Model
Model Introduction
This case study demonstrates the application of our Gla knockout (KO) mouse model for the preclinical efficacy assessment of a novel gene therapy for Fabry disease (FD). FD is an X-linked lysosomal storage disorder caused by mutations in the GLA gene, leading to a deficiency of the enzyme α-galactosidase A (α-Gal A) and subsequent accumulation of globotriaosylceramide (Gb-3). Our model, generated via targeted deletion of exons 2-3 in the endogenous Gla gene on a C57BL/6 background, recapitulates the key biochemical hallmark of the disease: a complete lack of α-Gal A activity.
Methodology
- Animal Model: Gla KO mice on a C57BL/6N or C57BL/6J background.
- Modeling Method: The model was created by embryonic stem cell gene targeting or gene editing-mediated deletion of exons 2-3 of the endogenous Gla gene, resulting in complete deficiency of α-galactosidase A (α-Gal A) activity.
- Therapeutic Intervention: To evaluate a potential therapy, researchers administered a single systemic dose of AAV2/8-hGLA (a recombinant adeno-associated virus vector carrying the human GLA gene) at four escalating concentrations: 0.75, 1, 2.5, and 5 × 1012 vg/kg.
- Efficacy Endpoint: α-Gal A enzymatic activity was measured in key target tissues (heart, kidney, spleen) to quantify dose-dependent restoration of enzyme function.
Efficacy Analysis & Results
The AAV2/8-hGLA gene therapy demonstrated a clear and potent dose-dependent restoration of enzymatic activity in the Gla KO mice (Fig.2).
- Dose-Dependent Enzyme Restoration: Analysis of heart, kidney, and spleen tissues revealed a significant, progressive increase in α-Gal A activity with each escalating dose of AAV2/8-hGLA (Fig.2A-C).
- Target Tissue Engagement: The robust increase in α-Gal A activity across all three critically affected organs confirms successful transduction and transgene expression, indicating the therapy's potential to reverse the underlying biochemical defect in Fabry disease (FD).
Fig.2 Dose-dependent efficacy of AAV2/8-hGLA gene therapy in Gla KO mice. α-Gal A activity was significantly restored in (A) heart, (B) kidney, and (C) spleen tissues following a single administration of the therapy. Data are presented as mean ± SD (n=5-8). *p < 0.05, **p < 0.01, ***p < 0.001 vs. Vehicle-treated KO group.
Conclusion
This case study successfully validates the Gla KO mouse as a highly predictive preclinical model for screening Fabry disease (FD) therapeutics. The data robustly demonstrate that our model is responsive to intervention, as shown by the dose-dependent restoration of α-Gal A activity following AAV gene therapy. These results highlight the critical role of this animal model in:
- Quantifying Therapeutic Efficacy: Precisely evaluating the dose-response relationship of novel treatments.
- De-risking Clinical Translation: Providing compelling in vivo proof-of-concept data to support the advancement of gene therapies into clinical trials.
Contact Us
Specializing in preclinical research, Protheragen leverages advanced genetic engineering technology platform to develop highly precise animal models. These models are instrumental in advancing pharmacodynamic (PD), pharmacokinetic (PK), and toxicology studies, thereby accelerating 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
- Montes M M, Castellanos L C S, Malnati G O M, et al. ASIC1a-associated mechanical hypersensitivity in the GlaKO Fabry disease mouse model[J]. Neurobiology of Pain, 2025: 100189.