Oral inoculation of sheep with the agent of bovine spongiform encephalopathy (BSE). 1. Onset and distribution of disease-specific PrP accumulation in brain and viscera
Oral inoculation of sheep with the agent of bovine spongiform encephalopathy (BSE). 1. Onset and distribution of disease-specific PrP accumulation in brain and viscera
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DOI：
10.1053/jcpa.2001.0465
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发表时间：
2001-05-01
影响因子：
0.8
通讯作者：
Bellworthy, SJ
中科院分区：
文献类型：
--
作者：
Jeffrey, M;Ryder, S;Bellworthy, SJ
六十三罗姆尼羊年龄6个月，由三组（PrPARQ/ARQ，PrPARQ/ARR，和PrPARR/ARR基因型）的21只动物，口服感染BSL感染牛的脑组织。将21只PrPARQ/ARQ动物的亚组与未感染的对照组4、10一起处死。接种后16、22或24-28个月（完全临床疾病发展后）（mpi）。免疫组织化学检查显示，在4或10 mpi时杀死的两组各有一只羊在单个淋巴结中具有疾病特异性PrP积累。在16 mpi时，四只感染羊中的两只在某些内脏、脊髓和脑中检测到这种积累。在22 MPI，五只感染羊中有三只在检查的所有组织中具有广泛的疾病特异性PrP积累。但其余两只动物仅在中枢神经系统中得到阳性结果。20-28 mpi时出现临床病变。三只羊被杀的先进的临床症状表现出广泛的PrP积累在脑，脊髓和外周组织。这些结果证实了PrPARQ/ARQ罗姆尼羊对BSE因子的实验感染易感。不同的网站在最初的PrP积累检测表明，感染的进入点不同。然而，一旦建立，感染似乎迅速蔓延到整个淋巴网状系统。结果，表明，在一些疯牛病感染的羊神经侵袭发生在没有检测到的PrP积累在内脏或周围神经系统。与牛疯牛病相反，然而，大多数绵羊表现出疾病特异性的PrP积累在淋巴网状系统。在这方面。疯牛病感染类似羊瘙痒病感染的羊，这是可能的，但是，未来的研究将揭示在淋巴网状和外周神经system.The PrPARQ/ARQ和PrPARR/ARR羊的细胞类型的靶向方面的差异也被杀死的亚组，在接种后的时间间隔。然而，高达24 mpi，这些动物都没有表现出疾病特异性PrP积累。稍后将报告进一步结果。
Sixty-three Romney sheep aged 6 months, consisting of three groups (PrPARQ/ARQ, PrPARQ/ARR, and PrPARR/ARR genotypes) of 21 animals, were infected orally with brain tissue from BSL-infected cattle. Sub-groups of the 21 PrPARQ/ARQ animals were killed, together with uninflected control, 4, 10. 16, 22 or 24-28 (after the development of full clinical disease) months post-inoculation (mpi). One sheep from each of the two groups of four killed at 4 or 10 mpi were shown by immunohistochemical examination to possess disease-specific PrP accumulations in single lymph nodes. At 16 mpi, such accumulations were detected ill two of four infected sheep in some viscera and in the spinal cord and brain. At 22 mpi, three of five infected sheep had widespread disease-specific PrP accumulations in all tissues examined. but the remaining two animals gave positive results only in the central nervous system. Clinical disease appeared at 20-28 mpi. Three sheep killed with advanced clinical signs showed widespread PrP accumulation in brain, spinal cord and peripheral tissues. These results confirmed that PrPARQ/ARQ Romney sheep arc susceptible to experimental infection with the BSE agent. The different sites at which initial PrP accumulations were detected suggested that the point of entry of infection varied. Once established, however, infection appeared to spread rapidly throughout the lymphoreticular system. The result,; suggested that in some BSE-infected sheep neuroinvasion occurred in the absence of detectable PrP accumulations in the viscera or peripheral nervous system. In contrast to cattle with BSE, however, most sheep showed disease-specific PrP accumulations in the lymphoreticular system. In this respect. BSE-inflected resembled scrapie-infected sheep; it is possible, however, that future research will reveal differences in respect of targeting of cell types within the lymphoreticular and peripheral nervous systems.The PrPARQ/ARQ and PrPARR/ARR sheep were also killed in sub-group, at intervals after inoculation. Up to 24 mpi, however, none of these animals showed disease-specific PrP accumulations. Further results will be reported later.