The Prion Protein Knockout Mouse
The Prion Protein Knockout Mouse
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朊病毒蛋白敲除小鼠
作者：
Andrew D. Steele;S. Lindquist;A. Aguzzi
朊病毒病的关键致病事件涉及细胞朊蛋白（PrP）的错误折叠和聚集。除了这个基本的观察，PrP在神经元中错误折叠导致损伤和死亡的机制仍然是谜。朊病毒毒性可能是通过破坏PrP的正常功能而产生的。如果是这样，了解PrP的正常功能可能有助于阐明朊病毒病的分子机制。切除Prnp基因（编码PrP）有助于确定PrP的持续产生对复制朊病毒感染性至关重要。由于PrP的结构没有提供任何提示其可能的功能，并且在PrP KO小鼠中没有明显的表型，因此PrP功能的研究通常依赖于直觉和偶然发现。在这里，我们列举了众多的表型中描述的PrP缺陷小鼠，其中许多只表现出生理挑战。我们讨论了多效性表型的PrP缺陷小鼠的可能的正常功能的PrP。关键的问题仍然是开放的：这些表型是PrP缺失的主要影响，他们告诉我们什么PrP的功能？
The key pathogenic event in prion disease involves misfolding and aggregation of the cellular prion protein (PrP). Beyond this fundamental observation, the mechanism by which PrP misfolding in neurons leads to injury and death remains enigmatic. Prion toxicity may come about by perverting the normal function of PrP. If so, understanding the normal function of PrP may help to elucidate the molecular mechansim of prion disease. Ablation of the Prnp gene, which encodes PrP, was instrumental for determining that the continuous production of PrP is essential for replicating prion infectivity. Since the structure of PrP has not provided any hints to its possible function, and there is no obvious phenotype in PrP KO mice, studies of PrP function have often relied on intuition and serendipity. Here, we enumerate the multitude of phenotypes described in PrP deficient mice, many of which manifest themselves only upon physiological challenge. We discuss the pleiotropic phenotypes of PrP deficient mice in relation to the possible normal function of PrP. The critical question remains open: which of these phenotypes are primary effects of PrP deletion and what do they tell us about the function of PrP?