Tanz Centre for Research in Neurodegenerative Diseases and Department of Biochemistry, University of Toronto, Toronto, Ontario M5T 2S8, Canada.
Institute for Neurodegenerative Diseases, Departments of Neurology and Biochemistry and Biophysics, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California 94143.
Cold Spring Harb Perspect Med. 2017 Nov 1;7(11):a027151. doi: 10.1101/cshperspect.a027151.
The inherited prion protein (PrP) prion disorders, which include familial Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker disease, and fatal familial insomnia, constitute ∼10%-15% of all PrP prion disease cases in humans. Attempts to generate animal models of these disorders using transgenic mice expressing mutant PrP have produced variable results. Although many lines of mice develop spontaneous signs of neurological illness with accompanying prion disease-specific neuropathological changes, others do not. Furthermore, demonstrating the presence of protease-resistant PrP species and prion infectivity-two of the hallmarks of the PrP prion disorders-in the brains of spontaneously sick mice has proven particularly challenging. Here, we review the progress that has been made toward developing accurate mouse models of the inherited PrP prion disorders.
遗传性朊病毒蛋白（PrP）朊病毒病，包括家族性克雅氏病、格斯特曼-施特劳斯勒-舍林氏病和致死性家族性失眠症，构成人类所有 PrP 朊病毒病病例的约 10%-15%。使用表达突变型 PrP 的转基因小鼠来生成这些疾病的动物模型的尝试产生了不同的结果。尽管许多小鼠品系会自发出现神经疾病症状，并伴有朊病毒病特异性神经病理学变化，但其他品系则不会。此外，证明自发患病小鼠脑中存在蛋白酶抗性 PrP 物种和朊病毒感染性——这是 PrP 朊病毒病的两个特征——尤其具有挑战性。在这里，我们回顾了在开发遗传性 PrP 朊病毒病准确小鼠模型方面取得的进展。
