Newest results of our R&D team at Scantox validate severe and very early motor deficits in hA53Ttg mice, making this model well-suited for preclinical Parkinson’s disease (PD) research.
PD belongs to the most devastating neurodegenerative diseases of the 21st century. The development of new drugs halting disease progression is therefore the main focus of PD research. To be able to test these new drugs, appropriate animal models are needed. The hA53Ttg α-synuclein transgenic mouse model expresses A53T mutant human α-synuclein under the control of the murine Thy-1 promoter and mimics the most crucial phenotypic symptoms. It therefore and belongs to the best PD models available.
Behavioral analysis of hA53Ttg mice at 3 different age groups revealed an onset of motor deficits already at the age of 2 months as analyzed with the beam walk test (Fig. 1A, B). The time to traverse the beam as well as the number of slips while walking over the beam was significantly increased in hA53Ttg mice compared to non-transgenic (ntG) littermates at the age of two months. With increasing age, hA53Ttg mice performed even worse in these parameters while ntgs presented a stable performance. Evaluation of hA53Ttg mice in the RotaRod test showed first significant deficits at the age of 4 months (Fig. 1C) and thus later compared to the beam walk test.
Evaluation of motor strength in the wire hanging test of hA53Ttg mice revealed very severe deficits already at the age of 2 months that did not further increase with age (Fig. 2A). Finally, hA53Ttg mice were evaluated for orofacial deficits in the pasta gnawing test. Evaluation of bites per episode showed, that hA53Ttg mice perform significantly worse compared to ntg littermates at the age of 4 months (Fig. 2B). Due to a decrease in performance of ntg mice at older age, this difference fades with age.
In conclusion, these results show, that hA53Ttg mice present a very severe motor phenotype including muscle weakness and orofacial muscle deficits.
Figure 1: Motor deficits in the beam walk and RotaRod test of hA53Ttg mice compared to non-transgenic 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.
Figure 2: Muscle strength and motor deficits in the wire hanging test and pasta gnawing test of hA53Ttg mice compared to non-transgenic 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.
