The new line of genetically modified mice with constitutive knockout of the gene alpha synuclein to study pathogenetic aspects of differential loss of dopaminergic neurons .

T V Tarasova, A A Ustyugov, N N Ninkina, V I Skvortsova
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Abstract

The purpose: This study investigated the role of alpha-synuclein in the development of dopaminergic neurons.

Methods: In this study a new SNCA knockout mouse line has been used to model the deficiency of alpha-synuclein function. In the knockout and control mice the dynamics of the formation of two distinct populations of dopaminergic neurons differently affected in patients with PD was studied by the comparative morphometric analysis.

Results: Here, we revealed a prominent modulating effect of alpha-synuclein on the developing DA neurons in substantia nigra (SN) which is the most affected region in PD patients. Yet, alpha-synuclein had no effect on the formation of DA neurons in ventral tegmental area which is much less susceptible to degeneration in PD patients.

Conclusion: The new line of knockout mice is a convenient model for studying pathophysiologic aspects of selective impairment of DA neurons.

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通过敲除α -突触核蛋白基因来研究多巴胺能神经元差异缺失的致病机制。
目的:探讨α -突触核蛋白在多巴胺能神经元发育中的作用。方法:本研究采用一种新的SNCA基因敲除小鼠系来模拟α -突触核蛋白功能缺失。通过比较形态计量学分析,在敲除小鼠和对照小鼠中,研究了PD患者两种不同群体多巴胺能神经元的形成动力学。结果:我们发现α -突触核蛋白对PD患者受影响最大的黑质(SN) DA神经元的发育具有显著的调节作用。而α -突触核蛋白对PD患者不易变性的腹侧被盖区DA神经元的形成没有影响。结论:新敲除小鼠系是研究DA神经元选择性损伤病理生理方面的方便模型。
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