Glutaric Acidemia Type 1 (GA1) Animal Model Service
Animal models of glutaric acidemia type 1 (GA1) faithfully replicate the pathophysiology of the human disease and are important tools for evaluating new therapeutics. Protheragen offers comprehensive animal model development services for GA1, providing researchers with genetically precise and pathologically faithful in vivo systems to accelerate therapeutic discovery and validation.
Introduction to Glutaric Acidemia Type 1 (GA1) Animal Models
Glutaric acidemia type 1 (GA1) animal models, primarily genetically engineered murine models, are indispensable preclinical tools designed to recapitulate the human disease's pathophysiology. The most widely utilized models involve the targeted disruption or specific mutation of the glutaryl-CoA dehydrogenase (Gcdh) gene, creating a biochemical phenotype that mirrors the metabolite accumulation seen in patients. These models are characterized by elevated levels of glutaric acid and 3-hydroxyglutaric acid in their tissues and bodily fluids.
Fig.1 Systemic delivery of AAV-GCDH ameliorates HLD-induced phenotype in a glutaric aciduria type I (GA1) mouse model. (Mateu-Bosch A, et al., 2024)
Our Services
At Protheragen, we provide comprehensive and sophisticated animal model development services for glutaric acidemia type 1 (GA1) research, empowering scientists worldwide to accelerate the discovery of novel therapeutic interventions. Our team delivers highly validated, pathologically accurate GA1 models using advanced technologies and deep expertise, providing a robust foundation for disease mechanism studies, biomarker identification, and drug efficacy testing.
Animal Models of Glutaric Acidemia Type 1 (GA1)
| Model Name | Modeling Method | Sales Status | Detailed Description |
| Gcdh-KO Mice | Knockout | Embryo Cryopreservation | Exon 3-7 of Gcdh gene was deleted to generate Gcdh knockout mice. |
| Ghr-Flox Mice | Conditional Knockout | Sperm Cryopreservation | These mice carry loxP sites flanking Exon 4 of Ghr gene. When crossed with a Cre recombinase-expressing strain, this strain is useful in eliminating tissue-specific conditional expression of Ghr gene. |
Case Study-Gcdhki/ki Rat Model
Model Introduction
Glutaric acidemia type 1 (GA1) is an inherited metabolic disorder caused by deficient activity of glutaryl-CoA dehydrogenase (GCDH), leading to the accumulation of neurotoxic metabolites. To establish a genetically accurate platform for investigating GA1 pathophysiology and evaluating therapeutic strategies, this study developed and characterized a novel knock-in rat model carrying the disease-associated p.R411W mutation (orthologous to human p.R402W) in the endogenous Gcdh gene.
Methodology
- Animal Model: Sprague-Dawley Gcdhki/ki homozygous knock-in rats and wild-type (WT) controls.
- Modeling Method: The model was created using gene editing to introduce the p.R411W point mutation into the endogenous Gcdh gene of Sprague-Dawley rats, ensuring precise genetic modeling of the human GA1 condition.
- Phenotypic Analysis Method: GCDH enzymatic activity was quantitatively measured in homogenates from multiple tissues (brain, heart, kidney, liver) of 6-week-old animals to evaluate the functional impact of the mutation.
Phenotypic Analysis & Results
Biochemical analysis confirmed a significant and tissue-specific GCDH deficiency in the Gcdhki/ki rats, effectively modeling key aspects of GA1.
- Significant Enzyme Deficiency: GCDH activity was significantly reduced in the heart, kidney, and liver of Gcdhki/ki rats compared to WT controls (Fig.2).
- Tissue-Specific Enzyme Profile: Consistent with the known metabolic profile in GA1, there was no significant difference in GCDH activity in the brain between WT rats and Gcdhki/ki rats, indicating that brain GCDH activity is very low (Fig.2).
Fig.2 Tissue-specific GCDH deficiency in Gcdhki/ki (KI) rats. Data are presented as mean ± SD (n=4). *p < 0.05, **p < 0.01 vs. wild-type (WT).
Conclusion
This case study validates the Gcdhki/ki rat as a highly relevant and genetically accurate model for glutaric acidemia type 1 (GA1) research. The model recapitulates the tissue-specific enzymatic deficiency characteristic of the human disease, providing a crucial preclinical tool for investigating GA1 disease mechanisms and evaluating novel therapeutic strategies aimed at correcting the systemic metabolic imbalance.
Contact Us
Leveraging precise animal models, Protheragen is dedicated to providing a comprehensive suite of preclinical research services for glutaric acidemia type 1 (GA1). 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
- Mateu-Bosch A, Segur-Bailach E, Muñoz-Moreno E, et al. Systemic delivery of AAV-GCDH ameliorates HLD-induced phenotype in a glutaric aciduria type I mouse model[J]. Molecular Therapy Methods & Clinical Development, 2024, 32(3).