Kojima N, Wang J, Mansuy I M, Grant S G, Mayford M, Kandel E R
Laboratory of Neurochemistry, National Institute for Physiological Sciences, Okazaki 444, Japan.
Proc Natl Acad Sci U S A. 1997 Apr 29;94(9):4761-5. doi: 10.1073/pnas.94.9.4761.
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 IIalpha 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.
为了研究Fyn酪氨酸激酶在神经元中的生理作用，我们构建了转基因小鼠，其在钙/钙调蛋白依赖性蛋白激酶IIα启动子的控制下表达fyn cDNA。利用这个启动子，我们在新生小鼠大脑中仅检测到Fyn的低表达。相反，在成年前脑的神经元中fyn转基因有强烈表达。为了确定在成年fyn缺陷小鼠中观察到的长时程增强（LTP）损伤是直接由成年海马神经元中Fyn的缺乏引起的，还是由神经元发育损伤间接引起的，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构建了fyn拯救小鼠。在fyn拯救小鼠中，即使fyn缺陷小鼠特有的形态学异常仍然存在，Schaffer侧支LTP也得以恢复。这些结果表明，Fyn至少部分地参与了LTP诱导的分子机制。
