Cain D P, Grant S G, Saucier D, Hargreaves E L, Kandel E R
Department of Psychology, University of Western Ontario, London, Canada.
Epilepsy Res. 1995 Oct;22(2):107-14. doi: 10.1016/0920-1211(95)00029-1.
To identify specific genes involved with epileptogenesis kindling was examined in mice carrying mutations engineered by gene targeting. Amygdala kindling was tested in mice with a null-mutation in the Fyn tyrosine kinase gene, a mutation that raises the threshold for the induction of long-term potentiation in the hippocampus. The fyn mutants had a normal threshold, duration and stability of epileptiform after-discharge, which is crucial for kindling. Despite the normal after-discharge, fyn mutants showed a striking retardation in the rate of kindling. Once the kindled state was established in fyn mutants it remained stable. This implicates a Fyn-dependent biochemical pathway in the induction but not the maintenance of normal amygdala kindling. fyn is the first gene identified to be required for normal epileptogenesis.
为了鉴定与癫痫发生相关的特定基因，我们在携带通过基因靶向工程改造的突变的小鼠中检测了点燃现象。在Fyn酪氨酸激酶基因发生无效突变的小鼠中测试杏仁核点燃，该突变提高了海马体中长时程增强诱导的阈值。Fyn突变体的癫痫样放电后发放的阈值、持续时间和稳定性正常，这对点燃至关重要。尽管放电后正常，但Fyn突变体在点燃速率上表现出明显延迟。一旦在Fyn突变体中建立了点燃状态，它就保持稳定。这表明在正常杏仁核点燃的诱导而非维持过程中存在一条依赖Fyn的生化途径。Fyn是第一个被鉴定为正常癫痫发生所必需的基因。
