Asante Emmanuel A, Li Yuan-Gen, Gowland Ian, Jefferys John G R, Collinge John
MRC Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK.
Neurosci Lett. 2004 Apr 22;360(1-2):33-6. doi: 10.1016/j.neulet.2004.01.049.
Infectious prion diseases may be acquired, sporadic or inherited in their aetiology. Inherited prion diseases are caused by coding mutations in the prion protein (PrP) gene. We investigated whether one of the commonest of these mutations, E200K, results in a functionally inactive prion protein by expressing human PrP 200K in transgenic mice homozygous for murine PrP null alleles. We examined the intrinsic properties of hippocampal CA1 pyramidal cells in these mice by measuring the resting potential, time constants and amplitude of the slow after-hyperpolarisation (AHP). These mice show rescue of the reduced slow AHP electrophysiological phenotype found in PrP null mice. Using the AHP as a marker for PrP function, we conclude that this pathogenic PrP mutation, does not significantly affect the normal neuronal function of PrP.
传染性朊病毒病在病因上可能是获得性、散发性或遗传性的。遗传性朊病毒病由朊病毒蛋白（PrP）基因的编码突变引起。我们通过在纯合鼠PrP无效等位基因的转基因小鼠中表达人PrP 200K，研究了这些突变中最常见的一种，即E200K，是否导致功能失活的朊病毒蛋白。我们通过测量静息电位、时间常数和慢后超极化（AHP）的幅度，研究了这些小鼠海马CA1锥体神经元的内在特性。这些小鼠显示出PrP无效小鼠中发现的慢AHP电生理表型降低得到了挽救。以AHP作为PrP功能的标志物，我们得出结论，这种致病性PrP突变不会显著影响PrP的正常神经元功能。
