hA53Ttg α-synuclein transgenic mice express human α-synuclein with A53T mutation under the control of the murine Thy-1 promoter.
hA53Ttg mice present an early motor phenotype that is measurable as early as 2 months of age. Several motor tests can be applied to evaluate muscle strength and motor deficits.
The most important characteristics of hA53Ttg mice are:
- Muscle weakness
- Motor deficits
- Increased α-synuclein and pSer129 α-synuclein levels
- Increased neurofilament light chain levels
- Neuroinflammation
First deficits of hA53Ttg mice in the beam walk test can be observed already at 2 months of age. Deficits in the RotaRod test are significant starting at the age of 4 months.
Figure 1: Motor deficits in the beam walk and RotaRod test of hA53Ttg mice compared to non-transgenic (ntg) littermates. Time to traverse the beam (A) and number of slips (B) in the beam walk test as well as time to fall off the rod in the RotaRod test (C). n = 23-24 per group. Two-way ANOVA with Bonferroni’s post hoc test; mean + SEM; ***p<0.001.
Severe muscle weakness of hA53Ttg mice as measured with the wire hanging test can already be observed at the age of 2 months. Orofacial deficits in the pasta gnawing test are measurable at the age of 4 months.
Figure 2: Muscle strength in the wire hanging test and orofacial motor deficits in the pasta gnawing test of hA53Ttg mice compared to non-transgenic (ntg) littermates. Wire hanging time observed in the wire hanging test (A) and bites per episode in the pasta gnawing test (B). n = 23-24 per group. Two-way ANOVA with Bonferroni’s post hoc test; mean + SEM; **p<0.01; ***p<0.001.
QPS Neuropharmacology offers a custom-tailored study design for hA53Ttg mice, and we are flexible to accommodate to your special interest. We are also happy to advise you and propose study designs. hA53Ttg mice show a relevant Parkinson’s disease (PD) phenotype at the age of 2 months. This grants a remarkable fast processing time of your PD study. Furthermore, non-transgenic littermates are available as control animals needed for proper study design.
We are happy to evaluate the efficacy of your compound in the hA53Ttg mouse model! The most common readouts are:
- Muscle weakness
- Motor deficits
- α-synuclein and pSer129 α-synuclein expression levels
- Neurofilament light chain levels