Animal Models for Tay-Sachs Disease
Since Tay-Sachs disease (TSD) is relatively rare in humans, animal models are indispensable tools for further studies of this disease. The information and experimental data obtained from preclinical studies using animal models are essential for advancing experimental therapies for TSD to clinical applications. Our company is committed to helping clients develop TSD animal models to study disease pathogenesis, test potential therapies, and evaluate the safety and efficacy of new drugs. We provide custom solutions, clinically meaningful animal models, and comprehensive data analysis and interpretation to help our clients make informed decisions about TSD drug development.
TSD is a rare autosomal recessive lysosomal storage metabolic disorder that results in progressive impairment of neurological function. The disease is caused by beta-hexosaminidase A (HexA) enzyme deficiency, which leads to the accumulation of GM2 gangliosides in the brain and other tissues, ultimately causing muscle weakness, ataxia, speech, and mental disorders. The disease is usually fatal and death usually occurs in early childhood. There is currently no cure for TSD and treatment is largely supportive.
Spontaneously developed TSD has been identified in several animal species, such as the flamingo Phoenicopterus ruber and Jacob sheep. These affected animals are characterized by a deficiency in HexA enzyme activity and an accumulation of GM2 gangliosides. The selection of animal models with clinical manifestations that most closely resemble the pathological features of humans is essential for the study of the pathogenesis and treatment of human TSD.
Fig. 1 Representative animal models of GM2 gangliosidosis. (Lawson C A, et al., 2016)
Disease Modeling Services
Our team of highly skilled scientists can work with you to develop custom animal models that closely mimic the TSD phenotype using state-of-the-art genetic engineering techniques. In addition, we provide clients with naturally occurring TSD animal models for preclinical research. Our disease models include, but are not limited to:
- TSD mouse model
We help our clients generate double-knockout mice deficient in HEXA and sialidase NEU3 genes. These HEXA/NEU3-deficient mice exhibit progressive neurodegeneration, skeletal structural abnormalities, and neurological abnormalities and are suitable models for studying new TSD therapies.
- Jacob sheep model
In Jacob sheep, TSD clinical and pathological features closely resemble human late-onset TSD. We provide our clients with sheep with TSD to build research models of TSD with measurable clinical symptoms.
- In vitro models
In addition to animal models, we also provide clients with an in vitro model of induced pluripotent stem cells (iPSC) derived from infant TSD patient fibroblasts to study the efficacy of new TSD therapies.
Preclinical Research Services
Our animal models can be utilized for testing a variety of potential therapies for TSD, including substrate reduction therapy (SRT), enzyme replacement therapy (ERT), bone marrow transplantation, gene therapy, and genetically modified multipotent cells. We provide extensive preclinical research services such as neurological assessment, behavior testing, and MRI to help customers understand disease progression and track the efficacy of new therapies. Our services include, but are not limited to:
- Thin-layer chromatography and mass spectrometric analysis
- Histological and immunohistochemical analysis
- Electron microscopic examination
- Passive avoidance test
- Morris water maze test
- Grip strength and open field test
Our company has over 20 years of experience in preclinical research and has a proven track record of success in developing animal models of rare diseases, including TSD. Our team of experts can provide a comprehensive range of services, including genetic engineering, animal breeding, and phenotypic analysis. If you are interested in our disease modeling services, please contact us for more information.
- Lawson, C. A.; Martin, D. R. Animal models of GM2 gangliosidosis: utility and limitations. The Application of Clinical Genetics, 2016: 111-120.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.