Parkinson’s Disease (PD) Models
Parkinson’s disease (PD) is a neurodegenerative disease characterized by movement disorder symptoms and a series of non-motor complications. The main clinical behavioral characteristics of PD patients include bradykinesia, resting tremor, rigidity, and gait abnormalities. The clinical pathological features mainly include degeneration of dopaminergic neurons in the substantia nigra pars compacta of the midbrain, decreased dopamine secretion in the striatum, and the accumulation of Lewy bodies in the nigrostriatal system.
The gene encoding α-synuclein, SNCA, has three main gene mutation sites: A53T (Ala-Thr), A30P (Ala-Pro) and E46K (Glu-Lys). These mutations can destroy the original molecular spatial structure and stability of the protein, causing α-synuclein to fail to degrade normally and abnormally aggregate to form amyloid structures, thereby causing neuronal degeneration and leading to PD. The specific knockout of Tfam in dopaminergic neurons will lead to mitochondrial DNA deletion, which will lead to functional impairment of dopaminergic neurons by affecting the electronic respiratory chain and inducing PD-like disease phenotypes.
GemPharmatech has developed four PD mouse models that can be utilized for the screening and safety evaluation of Parkinson’s disease treatments.
● Genetically Engineered PD Mouse Models
Strain No. | Strain Name | Strain Type | Description |
Transgenic | B6-hSNCA-A53T mice show a decline in motor function starting at 2 months of age, with human α-synuclein and p-S129 α-synuclein expression detectable in the brain. | ||
Transgenic | The B6-hSNCA-E46KA53T mouse model exhibits earlier onset of α-synuclein expression (at 1 month of age), higher aggregation levels, and more significant motor function decline compared to the B6-hSNCA-A53T mouse model. However, the median survival time is about 1-2 months longer than that of the B6-hSNCA-A53T strain, providing a longer therapeutic evaluation window. | ||
cKO | The Tfam cKO mice exhibit a reduction in dopaminergic neurons in the substantia nigra starting at 1 month of age. From 2 months of age, there is a decrease in dopamine and its metabolites in the striatum, along with a decline in motor function. |
● Induced PD Mouse Model
Model Name | Description |
6-OHDA Induced PD Mouse Model | The 6-OHDA induced PD mice exhibit motor deficits in the rotarod, grip strength, and gait analysis. Loss of dopaminergic neurons in the substantia nigra and striatum can be observed on the lesioned side. |
● PD Rat Model
In addition to these four mouse models, GemPharmatech has also successfully developed a PD rat model by precisely stereotaxically injecting 6-OHDA into both the Substantia Nigra pars compacta (SNc) and Ventral Tegmental Area (VTA). This well-constructed PD model offers a powerful tool for in-depth research and drug development, enabling a more comprehensive understanding and potential therapeutic interventions for PD.