Histopathology Facility, Instituto Gulbenkian de Ciência (IGC), 2780-156 Oeiras, Portugal.
Veterinary Medicine Department, University of Évora, 7004-516 Évora, Portugal.
Int J Mol Sci. 2021 Sep 28;22(19):10441. doi: 10.3390/ijms221910441.
Portugal was among the first European countries to report cases of Atypical Scrapie (ASc), the dominant form of Transmissible Spongiform Encephalopathy (TSE) in Portuguese small ruminants. Although the diagnostic phenotypes observed in Portuguese ASc cases seem identical to those described for Nor98, unequivocal identification requires TSE strain-typing using murine bioassays. In this regard, we initiated characterization of ASc isolates from sheep either homozygous for the ARQ genotype or the classical scrapie-resistant ARR genotype. Isolates from such genotypes were transmitted to TgshpXI mice expressing ovine PrPARQ. Mean incubation periods were 414 ± 58 and 483 ± 107 days in mice inoculated with ALRQ/AFRQ and ALRR/ALRR sheep isolates, respectively. Both isolates produced lesion profiles similar to French ASc Nor98 'discordant cases', where vacuolation was observed in the hippocampus (G6), cerebral cortex at the thalamus (G8) level, cerebellar white matter (W1) and cerebral peduncles (W3). Immunohistochemical PrP deposition was observed in the hippocampus, cerebellar cortex, cerebellar white matter and cerebral peduncles in the form of aggregates and fine granules. These findings were consistent with previously reported cases of ASc Nor98 transmitted to transgenic TgshpXI mice, confirming that the ASc strain present in Portuguese sheep corresponds to ASc Nor98.
葡萄牙是最早报告非典型痒病（ASc）病例的欧洲国家之一，ASc 是葡萄牙小反刍动物中传染性海绵状脑病（TSE）的主要形式。尽管在葡萄牙 ASc 病例中观察到的诊断表型似乎与诺福克痒病（Nor98）描述的表型相同，但需要使用鼠生物测定法进行 TSE 菌株分型才能明确识别。在这方面，我们开始对 ARQ 基因型或经典抗瘙痒病 ARR 基因型纯合的绵羊 ASc 分离株进行特征描述。从这些基因型的绵羊中分离出的毒株被传代到表达绵羊 PrPARQ 的 TgshpXI 小鼠中。接种 ALRQ/AFRQ 和 ALRR/ALRR 绵羊分离株的小鼠的平均潜伏期分别为 414±58 和 483±107 天。两种分离株产生的病变谱与法国 ASc Nor98“不一致病例”相似，在海马（G6）、丘脑（G8）水平的大脑皮层、小脑白质（W1）和大脑脚（W3）中观察到空泡化。在海马、小脑皮质、小脑白质和大脑脚中观察到 PrP 沉积的免疫组织化学形式为聚集体和细颗粒。这些发现与先前报道的 ASc Nor98 传播给转基因 TgshpXI 小鼠的病例一致，证实了葡萄牙绵羊中存在的 ASc 株与 ASc Nor98 相对应。
