DYRKIA BAC transgenic mice show altered synaptic plasticity with learning and memory defects
DYRKIA BAC transgenic mice show altered synaptic plasticity with learning and memory defects
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DOI：
10.1016/j.nbd.2005.12.006
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发表时间：
2006-06-01
影响因子：
6.1
通讯作者：
Song, Woo-Joo
中科院分区：
文献类型：
--
作者：
Ahn, Kyoung-Jin;Jeong, Hey Kyeong;Song, Woo-Joo
在唐氏综合征（DS）中观察到的各种表型中，精神发育迟滞是DS患者最常见和最令人衰弱的病症。人类染色体21q22.2上的DYRK1A基因编码蛋白激酶的亚家族，其显示双底物特异性并且已知在神经发育中起关键作用。为了研究DS精神发育迟滞，我们已经产生了转基因小鼠，在细菌人工染色体中仅含有一个完整的人类DYRK1A基因拷贝。转基因小鼠在Morris水迷宫中表现出明显的海马依赖性记忆障碍。有趣的是，我们观察到长时程增强和长时程抑制的变化，这表明DYRK1A在双向突触可塑性中的作用。这些小鼠代表了迄今为止临床上最相关的DYRK1A小鼠模型，并为我们提供了一个有价值的工具，在体内研究的机制，在DS的学习和记忆缺陷。(c)2005年爱思唯尔公司All rights reserved.
Among the various phenotypes seen in Down syndrome (DS), mental retardation is the most common and most debilitating condition suffered by individuals with DS. The DYRK1A gene on human chromosome 21q22.2 encodes a subfamily of protein kinases that displays dual substrate specificities and is known to play a critical role in neurodevelopment. To study DS mental retardation, we have generated transgenic mice that contain only one copy of the complete human DYRK1A gene in a bacterial artificial chromosome. The transgenic mice showed significant impairment in hippocampal-dependent memory tasks in a Morris water maze. Interestingly, we observed shifts in both long-term potentiation and long-term depression, which suggests a role for DYRK1A in bidirectional synaptic plasticity. These mice represent the most clinically relevant DYRK1A mouse model to date and provide us a valuable tool for the in vivo study of mechanisms that underlie the learning and memory deficit in DS. (c) 2005 Elsevier Inc. All rights reserved.