Department of Companion Animal Clinical Sciences, Faculty of Veterinary Medicine, Norwegian University of Life Sciences, Oslo, Norway.
Department of Basic Sciences and Aquatic Medicine, Faculty of Veterinary Medicine, Norwegian University of Life Sciences, Oslo, Norway.
FASEB J. 2020 Feb;34(2):2359-2375. doi: 10.1096/fj.201902588R. Epub 2019 Dec 13.
Studies in mice with ablation of Prnp, the gene that encodes the cellular prion protein (PrP ), have led to the hypothesis that PrP is important for peripheral nerve myelin maintenance. Here, we have used a nontransgenic animal model to put this idea to the test; namely, goats that, due to a naturally occurring nonsense mutation, lack PrP . Teased nerve fiber preparation revealed a demyelinating pathology in goats without PrP . Affected nerves were invaded by macrophages and T cells and displayed vacuolated fibers, shrunken axons, and onion bulbs. Peripheral nerve lipid composition was similar in young goats with or without PrP , but markedly different between corresponding groups of adult goats, reflecting the progressive nature of the neuropathy. This is the first report of a subclinical demyelinating polyneuropathy caused by loss of PrP function in a nontransgenic mammal.
在敲除编码细胞朊病毒蛋白（PrP）的 Prnp 基因的小鼠研究中，提出了 PrP 对于外周神经髓鞘维持很重要的假说。在这里，我们使用非转基因动物模型对这一观点进行了检验；即，由于天然发生的无义突变，导致羊缺乏 PrP。 teased 神经纤维制备显示，缺乏 PrP 的羊存在脱髓鞘病变。受影响的神经被巨噬细胞和 T 细胞浸润，并显示出空泡纤维、轴突萎缩和洋葱球。年轻的有或没有 PrP 的羊的外周神经脂质组成相似，但成年羊的相应组之间明显不同，反映了神经病变的进行性。这是首例在非转基因哺乳动物中由 PrP 功能丧失引起的亚临床脱髓鞘多发性神经病的报告。
