Analyses of neuropathogenic effects ofβsynuclein using a novel mouse model of synucleinopathies and post mortem brains

我们发现，表达dlb相关P123Hβs的转基因（tg）小鼠发生进行性神经退行性变，其特征是轴突肿胀、星形胶质细胞增生和行为异常，如记忆障碍。此外，P123Hβs tg小鼠与αs tg小鼠杂交后，神经变性表型显著增强，提示P123Hβs具有致病性，并与s协同刺激小鼠脑内神经变性。因此，p123h β stg小鼠有望成为阐明α-突触核蛋白病机制和开发新型治疗方法的宝贵工具。

We show that transgenic(tg) mice expressing DLB-linked P123Hβs develop progressive neurodegeneration, as characterized by axonal swelling, astrogliosis and behavioural abnormalities, such as memory disorder. Furthermore, cross-breeding of P123Hβs tg mice withαs tg mice, greatly enhanced neurodegeneration phenotypes, suggesting that P123Hβs is pathogenic and cooperates with s to stimulate neurodegeneration in mouse brain. Thus, it is expected that P123Hβs tg mice will be a invaluable tool for the elucidation of the mechanism and development of novel treatment forα-synucleinopathies.