Gaucher Disease Animal Model Service
Gaucher disease animal models are indispensable preclinical tools that recapitulate key disease features, enabling the study of pathogenesis and the evaluation of new therapeutics. Building on our pioneering expertise in Gaucher disease research, Protheragen leads in developing cutting-edge animal models that provide critical insights for disease study. As your dedicated partner, we deliver scientifically robust models to ensure your research objectives are met with precision and reliability.
Overview of Gaucher Disease Animal Models
Gaucher disease animal models are genetically engineered organisms, primarily rodents, that replicate the fundamental genetic defect of the human disease. These models are created to mimic the deficiency in glucocerebrosidase enzyme activity, leading to the characteristic accumulation of glucocerebroside. Their primary significance lies in serving as indispensable tools for deciphering disease mechanisms, studying progression across organs, and providing critical preclinical platforms for rigorously evaluating the efficacy and safety of potential new therapies.
Fig.1 Different animal models used to study mutant GBA1 variants associated with Gaucher disease (GD). (Cabasso O, et al., 2023)
Our Services
At Protheragen, we bridge the gap between research concept and clinical translation by providing genetically precise and phenotypically validated Gaucher disease animal models. Our end-to-end service, from custom model generation via advanced gene editing to comprehensive phenotypic and efficacy analyses, is designed to deliver robust, data-driven preclinical studies that accelerate your therapeutic development pipeline.
Animal Models of Gaucher Disease
Genetically Engineered Models
At the core of our service, Protheragen develops precise genetic models of Gaucher disease, including knock-in, knock-out, and conditional mutants, that faithfully mirror human pathology to accelerate the development of advanced therapeutics.
- Gba1 Knockout Model
- Gba1 Conditional Knockout Model
- Gba1 L444P and recNcil Knock-in Model
- Gba1 D409V Point Mutation Model
- D409V/null Model
- Other Models
Chemically Induced Models
Protheragen is committed to providing specialized chemically induced animal models of Gaucher disease to complement genetic models. These models primarily utilize enzyme inhibitors to rapidly replicate the biochemical hallmarks of the disease, enabling efficient therapeutic screening.
- Conduritol-B-epoxide (CBE) Induced Model
- Other Models
Gba-Flox Mice for Gaucher Disease Research
| Model Name | Gba-Flox Mice |
| Model Type | Genetically Engineered Mouse Model (GEMM) |
| Modeling Method | Conditional Knockout |
| Sales Status | Sperm Cryopreservation |
| Detailed Description | These mice carry loxP sites flanking exons 8-11 of the Gba gene. When crossed with a Cre recombinase-expressing strain, this strain helps eliminate tissue-specific conditional expression of the Gba gene. Gba-Flox (2) mice carry loxP sites flanking exons 6-8 of the Gba gene. |
Case Study-Humanized Gba1 F213I Knock-in Mouse Model
Model Introduction
This case study details the generation and biochemical validation of a humanized knock-in mouse model for Gaucher disease (GD). GD is a lysosomal storage disorder caused by mutations in the GBA1 gene, leading to deficient glucocerebrosidase (GCase) enzyme activity. To create a model with high clinical relevance, we engineered a mouse that carries a specific pathogenic point mutation (F213I) within the context of the human GBA1 gene sequence, replacing the corresponding murine genomic region.
Methodology
- Animal Model: C57BL/6J-Gba1F213I/F213I (F213I) mice and wild-type (WT) C57BL/6J controls.
- Modeling Method: The model was generated using embryonic stem (ES) cell-based homologous recombination. This precise genetic engineering strategy replaced exons 5-7 of the endogenous mouse Gba1 gene with the corresponding human exons harboring the F213I mutation. The Neomycin (Neo) selection cassette was subsequently excised via Flp recombinase to ensure proper genetic regulation.
- Phenotypic Analysis Method: GCase enzymatic activity was quantified in homogenates from key tissues (brain, liver, skin) on postnatal day 0 (P0) to assess the functional consequence of the F213I mutation.
Phenotypic Analysis & Results
Biochemical analysis of the Gba1F213I/F213I mice at birth confirmed a severe GCase deficiency, accurately modeling the human disease.
- Severe Enzyme Deficiency: GCase activity was markedly decreased in the brain, liver, and skin of Gba1F213I/F213I mice compared to wild-type controls (Fig.2).
- Clinical Relevance: The residual GCase activity in the Gba1F213I/F213I mice was quantified to be approximately 20% of normal levels. This profound reduction is consistent with the enzymatic activity values observed in human Gaucher disease patients carrying the homologous F213I mutation, validating the high translational fidelity of this model.
Fig.2 Profound glucocerebrosidase (GCase) deficiency in humanized Gba1F213I/F213I (F213I) mice. Data are presented as mean ± SEM (n=3).
Conclusion
This study establishes the humanized Gba1F213I/F213I mouse as a validated and critical model for studying the severe perinatal-onset forms of Gaucher disease. The model successfully recapitulates the profound enzymatic deficiency characteristic of the human condition, providing an essential, genetically accurate platform for investigating the pathophysiology of GBA1 mutations and for screening therapeutic interventions targeting the early stages of the disease.
Contact Us
To advance the commercialization of new therapies for Gaucher disease, Protheragen provides comprehensive animal models to facilitate pharmacodynamic (PD), pharmacokinetics (PK), and toxicology studies. If you are interested in our animal model development services, please do not hesitate to contact us for more details and quotation information.
Reference
- Cabasso O, Kuppuramalingam A, Lelieveld L, et al. Animal models for the study of Gaucher Disease[J]. International Journal of Molecular Sciences, 2023, 24(22): 16035.