Rescue of neurophysiological phenotype seen in PrP null mice by transgene encoding human prion protein
Rescue of neurophysiological phenotype seen in PrP null mice by transgene encoding human prion protein
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通过编码人朊病毒蛋白的转基因拯救 PrP 缺失小鼠的神经生理表型
作者：
M. Whittington;K. Sidle;I. Gowland;J. Meads;A. Hill;M. Palmer;John Gordon Ralph Jefferys;J. Collinge
朊病毒蛋白（PrP）是朊病毒疾病（人和动物的可传播的神经退行性疾病）的病因学的核心。PrP基因敲除小鼠表现出突触神经生理学异常，特别是GABAA受体介导的快速抑制减弱和海马长时程增强受损。在这里，我们证明，这种PrP空表型是拯救小鼠与高拷贝数的转基因编码人PrP，但不是在低拷贝数的小鼠，确认特异性的表型损失的功能PrP。人类PrP补偿鼠PrP损失的能力将允许直接研究导致遗传性朊病毒疾病的18种人类PrP突变的功能后果;这种表型现在可以形成PrP的第一个功能测定的基础。
The prion protein (PrP) is central to the aetiology of the prion diseases, transmissible neurodegenerative conditions of humans and animals. PrP null mice show abnormalities of synaptic neurophysiology, in particular weakened GABAA receptor–mediated fast inhibition and impaired long–term potentiation in the hippocampus. Here we demonstrate that this PrP null phenotype is rescued in mice with a high copy number of a transgene encoding human PrP but not in low copy number mice, confirming the specificity of the phenotype for loss of function of PrP. The ability of human PrP to compensate for loss of murine PrP will allow direct study of the functional consequences of the 18 human PrP mutations, which cause the inherited prion diseases; this phenotype can now form the basis of the first functional assay for PrP.
影响因子：
2.9
作者：
N. Stahl;D. Borchelt;S. Prusiner
通讯作者：
N. Stahl;D. Borchelt;S. Prusiner
链脲佐菌素糖尿病大鼠膀胱试纸的长度-张力关系。
影响因子：
3.1
作者：
Longhurst,PA;Kang,J;Wein,AJ;Levin,RM
通讯作者：
Levin,RM
DOI：
10.1073/pnas.90.9.4309
发表时间：
1993-05-01
影响因子：
11.1
作者：
HARRIS, DA;LELE, P;SNIDER, WD
通讯作者：
SNIDER, WD