State Key Laboratories for Agrobiotechnology, Key Lab of Animal Epidemiology and Zoonosis, Ministry of Agriculture, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China.
J Mol Neurosci. 2013 Oct;51(2):591-601. doi: 10.1007/s12031-013-0032-6. Epub 2013 May 30.
The 37/67-kDa laminin receptor precursor (LRP)/laminin receptor (LR) is a cell surface receptor for cellular prion proteins and misfolded pathological prions. Previous research has shown that blocking or decreasing LRP/LP levels by anti-LRP/LR antibodies or small interfering RNAs (siRNAs) can prolong the incubation phase of experimental prion infection. This study aimed to investigate potential mechanisms contributing to prion resistance/susceptibility by using the rabbit, a species unsusceptible to prion infection, as a model. We investigated the expression level and distribution of LRP/LR in rabbit tissues by real-time polymerase chain reaction and by immunochemical analysis with a monoclonal anti-67 kDa LR antibody. Our results showed LRP/LR mRNA expression in all the tissues examined. Very low LRP/LR expression levels were observed in central nervous system (CNS) tissues, whereas high expression levels were observed in reproductive and digestive tissues, which differed from the expression patterns that have been reported for prion-susceptible animals. The immunochemical staining results were generally consistent with the mRNA findings, although no LR protein was detected in CNS tissues. Our findings provide a basis for further studies on prion resistance in rabbits and other animal species.
37/67 kDa 层粘连蛋白受体前体 (LRP)/层粘连蛋白受体 (LR) 是细胞表面细胞朊病毒蛋白和错误折叠病理性朊病毒的受体。先前的研究表明,通过抗 LRP/LR 抗体或小干扰 RNA (siRNA) 阻断或降低 LRP/LP 水平可以延长实验性朊病毒感染的潜伏期。本研究旨在通过使用对朊病毒感染不易感的兔作为模型,来研究导致对朊病毒抗性/敏感性的潜在机制。我们通过实时聚合酶链反应和用单克隆抗 67 kDa LR 抗体进行免疫化学分析,研究了 LRP/LR 在兔组织中的表达水平和分布。我们的结果显示,在所检查的所有组织中均有 LRP/LR mRNA 的表达。中枢神经系统 (CNS) 组织中观察到 LRP/LR 的表达水平非常低,而生殖和消化组织中则观察到高表达水平,这与朊病毒易感动物的表达模式不同。免疫化学染色结果与 mRNA 结果基本一致,尽管 CNS 组织中未检测到 LR 蛋白。我们的研究结果为进一步研究兔和其他动物物种的朊病毒抗性提供了基础。