Dystonia Animal Model Service
Dystonia animal models are preclinical research tools that recapitulate key pathological features of human dystonia, including abnormal motor phenotypes and neural circuit dysfunction. Protheragen's team of distinguished researchers and scientists possesses profound expertise in dystonia research, demonstrating an unwavering commitment to pioneering precisely engineered animal models that accelerate therapeutic innovation in this critical field.
Introduction to Dystonia Animal Models
Dystonia animal models are indispensable preclinical tools developed to replicate the hallmark involuntary muscle contractions and abnormal postures seen in the human disorder. The core purpose of these models is to provide a validated in vivo system to elucidate the complex pathophysiology of dystonia, identify novel therapeutic targets, and rigorously test the efficacy and safety of potential pharmacological, genetic, or neuromodulatory treatments before they advance to clinical trials.
Fig.1 Mouse pup model of dystonia. (Van Der Heijden M E, et al., 2022)
Methods of Dystonia Animal Model Development
The development of robust animal models is fundamental to dystonia research, and the chosen method directly reflects the specific research question, whether it is to study genetic mechanisms or circuit dysfunction. The primary strategies for generating these models can be categorized into two main approaches:
Genetically Engineered Method
Genetically engineered models are created by directly altering the animal genome using transgenic or gene-editing techniques to introduce or mimic specific human dystonia-causing mutations, such as mutations in TOR1A or GNAL. These models are essential for studying the lifelong progression of the disease, understanding the underlying molecular pathophysiology, and for studying inherited dystonias in controlled systems.
Induced Method
Induced models involve disrupting neural circuits in otherwise healthy animals through external interventions such as targeted neurotoxin injections (e.g., 3-NP into the striatum) or surgical lesioning. These approaches are highly valuable for rapidly modeling circuit-specific dysfunction, replicating symptoms of acquired dystonia, and performing high-throughput screening of potential therapeutic compounds.
Our Services
Leveraging advanced technology and a dedicated team, Protheragen offers comprehensive animal model development services for dystonia research, supporting the advancement of therapeutic strategies for this complex movement disorder. Our expertise spans the broad spectrum of dystonia, from common focal forms to rare genetic subtypes such as DYT1 and DYT11. Our highly validated models recapitulate key neuropathological and behavioral phenotypes, making them indispensable tools for studying disease mechanisms, validating targets, and testing the efficacy of novel drugs or therapies.
Animal Models of Dystonia
Genetically Engineered Models
Leveraging our expertise in genetic engineering, Protheragen is capable of creating precise animal models that recapitulate the molecular and phenotypic hallmarks of human hereditary dystonias. Our portfolio includes, but is not limited to, the following key models:
- Dstdt-J Mouse Model
- dtsz Hamster Model
- Pnkd Mouse Model
- dt Rat Model
- Tottering Mouse Model
- Purkinje Cell Specific Tottering Mouse Model
Induced Models
In addition to genetic models, we also provide robust induced models of dystonia, which are invaluable for studying circuit dysfunction and screening therapeutic compounds. Our models include but are not limited to:
- 3-Nitropropionic Acid Induced Model
- Chronic Dopamine Therapy Induced Model
- Kainic Acid Induced Model
- Bicuculline Induced Model
- Muscimol Induced Model
- MPTP Induced Model
Sgce-KO (2) Mice for Dystonia Research
| Model Name | Sgce-KO (2) Mice |
| Model Type | Genetically Engineered Mouse Model (GEMM) |
| Modeling Method | Knockout |
| Targeted Disease | Myoclonic Dystonia 11 (DYT11) |
| Sales Status | Embryo Cryopreservation |
| Detailed Description | Exon 2-3 of Sgce gene was deleted to generate Sgce knockout mice. |
| Applications & Therapeutic Areas | The model is primarily used for evaluating therapeutics for myoclonic dystonia 11 (DYT11) and investigating the role of maternally imprinted ε-sarcoglycan gene dysfunction in movement disorders. |
Case Study-Kainic Acid-Induced Dystonia Mouse Model
- Species: C57BL/6J Mouse
- Modeling Method: This model induces dystonia by microinjecting the excitatory glutamate agonist kainic acid directly into the midline cerebellum of anesthetized mice.
- Treatment: To establish a dose-response curve, mice received injections of 0.5 μl of saline vehicle or kainic acid at concentrations of 10, 25, 50, and 100 μg/ml. To determine the neuroanatomical basis of kainic acid -induced dystonia, c-fos mRNA expression was assessed 2 hours after microinjection.
- Results: The dose-response curve showed that the severity of dystonia in mice increased linearly with dose, with a correlation coefficient of 0.97. The results of c-fos mRNA expression evaluation showed that c-fos expression in the cerebellum was dose-dependent. Significant increases in c-fos mRNA expression were also observed in the red nucleus and locus ceruleus.
Fig.2 (A) The dose-response curve after microinjection of kainic acid into the cerebellum of wild-type mice showed a positive correlation. (B) c-fos mRNA expression in the cortex, hippocampus, striatum, red nucleus, locus ceruleus, and cerebellum was assessed 2 hours after microinjection.
At Protheragen, we are committed to developing well-characterized animal models to facilitate preclinical research in dystonia, including 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
- Van Der Heijden M E, Gill J S, Rey Hipolito A G, et al. Quantification of behavioral deficits in developing mice with dystonic behaviors[J]. Dystonia, 2022, 1: 10494.