Behavioral abnormalities and Parkinson's-like histological changes resulting from Id2 inactivation in mice.
Behavioral abnormalities and Parkinson's-like histological changes resulting from Id2 inactivation in mice.
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DOI：
10.1242/dmm.010041
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发表时间：
2013-05
影响因子：
4.3
通讯作者：
Holroyd KB
中科院分区：
文献类型：
--
作者：
Havrda MC;Paolella BR;Ward NM;Holroyd KB
在新的遗传动物模型中表征多巴胺能神经元的发育和功能可能会为研究人员开发神经系统疾病的疾病修饰治疗方法提供策略。Id 2是在发育中的中枢神经系统中表达的转录因子。Id 2 −/−小鼠嗅球中的多巴胺能神经元较少，嗅觉辨别力降低，这是帕金森病的临床前标志物。在这里，我们总结了行为，组织学和体外分子生物学分析，以确定是否中脑多巴胺能神经元受到Id 2损失。Id 2 −/−小鼠在1个月和3个月大时表现出过度活跃，但在6个月大时表现出活动减少。Id 2 −/−小鼠表现出与自发活动变化相关的黑质丘脑部（SNpC）多巴胺能神经元的年龄依赖性组织学变化。在Id 2 −/−小鼠的早期观察到多巴胺转运蛋白（DAT）表达减少，并且DAT表达依赖于体外多巴胺能分化模型中的Id 2表达。在老年Id 2 −/−小鼠的SNpC中观察到神经变性的证据，包括活化的caspase-3和胶质细胞浸润。这些发现证明了Id 2在维持中脑多巴胺神经元中的新作用。Id 2 −/−小鼠应该为研究涉及多巴胺系统的神经退行性疾病的进展提供独特的机会。
Characterizing dopaminergic neuronal development and function in novel genetic animal models might uncover strategies for researchers to develop disease-modifying treatments for neurologic disorders. Id2 is a transcription factor expressed in the developing central nervous system. Id2−/− mice have fewer dopaminergic neurons in the olfactory bulb and reduced olfactory discrimination, a pre-clinical marker of Parkinson’s disease. Here, we summarize behavioral, histological and in vitro molecular biological analyses to determine whether midbrain dopaminergic neurons are affected by Id2 loss. Id2−/− mice were hyperactive at 1 and 3 months of age, but by 6 months showed reduced activity. Id2−/− mice showed age-dependent histological alterations in dopaminergic neurons of the substantia nigra pars compacta (SNpC) associated with changes in locomotor activity. Reduced dopamine transporter (DAT) expression was observed at early ages in Id2−/− mice and DAT expression was dependent on Id2 expression in an in vitro dopaminergic differentiation model. Evidence of neurodegeneration, including activated caspase-3 and glial infiltration, were noted in the SNpC of older Id2−/− mice. These findings document a novel role for Id2 in the maintenance of midbrain dopamine neurons. The Id2−/− mouse should provide unique opportunities to study the progression of neurodegenerative disorders involving the dopamine system.
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影响因子：
16.2
作者：
Giasson, BI;Duda, JE;Lee, VMY
通讯作者：
Lee, VMY
影响因子：
25
作者：
Li, Yanping;Liu, Wencheng;Oo, Tinmarla F.;Wang, Lei;Tang, Yi;Jackson-Lewis, Vernice;Zhou, Chun;Geghman, Kindiya;Bogdanov, Mikhail;Przedborski, Serge;Beal, M. Flint;Burke, Robert E.;Li, Chenjian
通讯作者：
Li, Chenjian
影响因子：
64.5
作者：
BENEZRA, R;DAVIS, RL;WEINTRAUB, H
通讯作者：
WEINTRAUB, H
影响因子：
6.1
作者：
BRACHA, HS;SHULTS, C;KLEINMAN, JE
通讯作者：
KLEINMAN, JE
影响因子：
3.6
作者：
Kurosaki, R;Muramatsu, Y;Araki, T
通讯作者：
Araki, T