Rescuing impairment of long-term potentiation in fyn-deficient mice by introducing Fyn transgene
Rescuing impairment of long-term potentiation in fyn-deficient mice by introducing Fyn transgene
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DOI：
10.1073/pnas.94.9.4761
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发表时间：
1997-04-29
影响因子：
11.1
通讯作者：
Kandel, ER
中科院分区：
文献类型：
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作者：
Kojima, N;Wang, J;Kandel, ER
为了检查Fyn酪氨酸激酶在神经元中的生理作用，我们产生了在钙/钙调蛋白依赖性蛋白激酶II α启动子控制下表达Fyn cDNA的转基因小鼠。使用该启动子，我们在新生儿脑中仅检测到Fyn的低表达。相反，在成年前脑的神经元中存在Fyn转基因的强表达，为了确定在成年fyn缺陷小鼠中观察到的长时程增强（LTP）的损害是由成年海马神经元中Fyn的缺乏直接引起的还是由神经元发育的损害间接引起的，我们通过将野生型fyn转基因导入携带内源性fyn基因靶向缺失的小鼠中来产生fyn拯救小鼠。在fyn拯救小鼠中，Schaffer侧枝LTP恢复，尽管Fyn缺陷小鼠的形态异常特征仍然存在，这些结果表明Fyn至少部分地参与了LTP诱导的分子机制。
To examine the physiological role of the Fyn tyrosine kinase in neurons, we generated transgenic mice that expressed a fyn cDNA under the control of the calcium/calmodulin-dependent protein kinase II alpha promoter, With this promoter, we detected only low expression of Fyn in the neonatal brain, In contrast, there was strong expression of the fyn-transgene in neurons of the adult forebrain, To determine whether the impairment of long-term potentiation (LTP) observed in adult fyn-deficient mice was caused directly by the lack of Fyn in adult hippocampal neurons or indirectly by an impairment in neuronal development, we generated fyn-rescue mice by introducing the wild-type fyn-transgene into mice carrying a targeted deletion in the endogenous fyn gene, In fyn-rescue mice, Schaffer collateral LTP was restored, even though the morphological abnormalities characteristic of fyn-deficient mice were still present, These results suggest that Fyn contributes, at least in part, to the molecular mechanisms of LTP induction.