Session Information
Date: Sunday, October 7, 2018
Session Title: Other
Session Time: 1:45pm-3:15pm
Location: Hall 3FG
Objective: The aim of this study is to create mouse models reproducing the course of PD pathology and symptoms.
Background: Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by a variety of motor and non-motor symptoms. The important pathologies of PD are the loss of dopaminergic neurons in the substantia nigra pars compacta (SNc) and the consequent loss of dopamine in the striatum, in association with Lewy bodies and Lewy neurites that are mainly composed of abnormally aggregated α-synuclein (α-syn). An appropriate animal model is essential not only to explore the pathogenesis but for the therapeutic intervention in PD. So far, genetic PD animal models have not completely recapitulated the whole process of aggregated α-syn progression in association with dopaminergic neuron loss.
Methods: We generated human α-syn bacterial artificial chromosome transgenic mice harboring the entire human α-syn gene and its gene expression regulatory regions with the A53T mutation which is a causative gene mutation for familial PD, a functional repeat polymorphism (REP1) in the α-Syn promoter region and single nucleotide polymorphisms (rs3857059 and rs11931074) which increase the risk of sporadic PD identified in GWAS-PD.
Results: A53T BAC tg mice expressed α-syn in a similar pattern with that of human α-syn. Abnormal phosphorylated α-syn was accumulated in the olfactory bulb, the cerebral cortex, the striatum, the substantia nigra pars compacta (SNc) and the dorsal motor nucleus of the vagus nerve. The number of tyrosine hydroxylase positive cells in SNc was decreased in an age-dependent manner. In the behavioral analyses, A53T BAC tg mice showed hyposmia, which is considered as prodromal symptom of PD.
Conclusions: A53T BAC tg mice can recapitulate the PD pathogenesis, especially in the early stage of PD. This novel tg mouse model is expected to be a valuable tool to tackle with the PD pathogenesis.
To cite this abstract in AMA style:
T. Taguchi, I. Masashi, M. Uemura, Y. Hatanaka, N. Uemura, H. Yamakado, R. Takahashi. A53T mutant human α-synuclein BAC transgenic mice as a model for Parkinson’s disease [abstract]. Mov Disord. 2018; 33 (suppl 2). https://www.mdsabstracts.org/abstract/a53t-mutant-human-%ce%b1-synuclein-bac-transgenic-mice-as-a-model-for-parkinsons-disease/. Accessed June 14, 2025.« Back to 2018 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/a53t-mutant-human-%ce%b1-synuclein-bac-transgenic-mice-as-a-model-for-parkinsons-disease/