Pathogenic human prion protein rescues PrP null phenotype in transgenic mice
Pathogenic human prion protein rescues PrP null phenotype in transgenic mice
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DOI：
10.1016/j.neulet.2004.01.049
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发表时间：
2004-04-22
影响因子：
2.5
通讯作者：
Collinge, J
中科院分区：
文献类型：
--
作者：
Asante, EA;Li, YG;Collinge, J
传染性先天疾病的病因可以是获得性、散发性或遗传性的。遗传性先天疾病是由先天蛋白（PrP）基因编码突变引起的。我们通过在小鼠PrP零等位基因纯合的转基因小鼠中表达人PrP 200K，研究了其中最常见的突变之一E200K是否会导致功能失活的先验蛋白。我们通过测量静息电位、时间常数和慢后超极化（AHP）振幅来检测这些小鼠海马CA1锥体细胞的内在特性。这些小鼠显示出在PrP缺失小鼠中发现的减少的缓慢AHP电生理表型的恢复。利用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。2004爱思唯尔爱尔兰有限公司版权所有。
Infectious priori diseases may be acquired, sporadic or inherited in their aetiology. Inherited priori diseases are caused by coding mutations in the priori protein (PrP) gene. We investigated whether one of the commonest of these mutations, E200K, results in a functionally inactive priori 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. (C) 2004 Elsevier Ireland Ltd. All rights reserved.