Konold Timm, Phelan Laura J, Donnachie Ben R, Chaplin Melanie J, Cawthraw Saira, González Lorenzo
Animal Sciences Unit, Animal and Plant Health Agency Weybridge, Addlestone, UK.
Pathology Department, Animal and Plant Health Agency Weybridge, Addlestone, UK.
BMC Vet Res. 2017 May 4;13(1):122. doi: 10.1186/s12917-017-1036-1.
A study to investigate transmission of classical scrapie via goat milk was carried out in sheep: firstly, lambs were challenged orally with goat scrapie brain homogenate to confirm transmission of scrapie from goats to sheep. In the second study phase, milk from scrapie-infected goats was fed to lambs. Lambs were selected according to their prion protein gene (PRNP) genotype, which was either VRQ/VRQ or ARQ/ARQ, with or without additional polymorphisms at codon 141 (FF, LF or LL) of the ovine PRNP. This report describes the clinical, pathological and molecular phenotype of goat scrapie in those sheep that progressed to clinical end-stage.
Ten sheep (six VRQ/VRQ and four ARQ/ARQ, of which three FF and one LL) challenged with one of two scrapie brain homogenates, and six pairs of sheep (ARQ, of which five LL and seven LF) fed milk from six different goats, developed clinical disease, which was characterised by a pruritic (all VRQ/VRQ and LL sheep) or a non-pruritic form (all LF and FF sheep). Immunohistochemical (IHC) examination revealed that the pattern of intra- and extracellular accumulation of disease-associated prion protein in the brain was also dependent on PRNP polymorphisms at codon 141, which was similar in VRQ and LL sheep but different from LF and FF sheep. The influence of codon 141 was also seen in discriminatory Western blot (WB), with LF and FF sheep showing a bovine spongiform encephalopathy-like profile (diminished reactivity with P4 antibody) on brain tissue. However, discriminatory WB in lymphoid tissues, and IHC pattern and profile both in lymphoid and brain tissue was consistent with classical scrapie in all sheep.
This study provided further evidence that the clinical presentation and the pathological and molecular phenotypes of scrapie in sheep are influenced by PRNP polymorphisms, particularly at codon 141. Differences in the truncation of disease-associated prion protein between LL sheep and those carrying the F allele may be responsible for these observations.
在绵羊中开展了一项研究，以调查经典痒病是否会通过山羊奶传播：首先，给羔羊口服山羊痒病脑匀浆，以确认痒病从山羊传播至绵羊。在第二个研究阶段，将感染痒病的山羊的奶喂给羔羊。根据羔羊的朊病毒蛋白基因（PRNP）基因型进行选择，其基因型为VRQ/VRQ或ARQ/ARQ，绵羊PRNP的第141密码子处有或无额外多态性（FF、LF或LL）。本报告描述了那些进展至临床终末期的绵羊中山羊痒病的临床、病理和分子表型。
用两种痒病脑匀浆之一进行攻击的10只绵羊（6只VRQ/VRQ和4只ARQ/ARQ，其中3只为FF，1只为LL），以及喂了来自6只不同山羊的奶的6对绵羊（ARQ，其中5只为LL，7只为LF）出现了临床疾病，其特征为瘙痒型（所有VRQ/VRQ和LL绵羊）或非瘙痒型（所有LF和FF绵羊）。免疫组化（IHC）检查显示，脑中疾病相关朊病毒蛋白的细胞内和细胞外积累模式也取决于第141密码子处的PRNP多态性，VRQ和LL绵羊中的情况相似，但与LF和FF绵羊不同。在鉴别性蛋白质印迹（WB）中也可见第141密码子的影响，LF和FF绵羊的脑组织呈现牛海绵状脑病样图谱（与P4抗体的反应性降低）。然而，淋巴组织中的鉴别性WB以及淋巴组织和脑组织中的IHC模式及图谱在所有绵羊中均与经典痒病一致。
本研究提供了进一步的证据，表明绵羊痒病的临床表现、病理和分子表型受PRNP多态性影响，尤其是第141密码子处的多态性。LL绵羊与携带F等位基因的绵羊之间疾病相关朊病毒蛋白截短的差异可能是造成这些观察结果的原因。
