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Exploration of genetic factors resulting in abnormal disease in cattle experimentally challenged with bovine spongiform encephalopathy

机译:畜牧业导致畜牧业疾病异常症状的探讨

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Since the discovery of bovine spongiform encephalopathy (BSE), researchers have orally challenged cattle with infected brain material to study various aspects of disease pathogenesis. Unlike most other pathogens, oral BSE challenge does not always result in the expected clinical presentation and pathology. In a recent study, steers were challenged orally with BSE and all developed clinical signs and were sacrificed and tested. However, despite a similar incubation and clinical presentation, one of the steers did not have detectable PrP Sc in its brain. Samples from this animal were analysed for genetic differences as well as for the presence of in vitro PrP Sc seeding activity or infectivity to determine the BSE status of this animal and the potential reasons that it was different. Seeding activity was detected in the brainstem of the abnormal steer but it was approximately one million times less than that found in the normal BSE positive steers. Intra-cranial challenge of bovinized transgenic mice resulted in no transmission of disease. The abnormal steer had different genetic sequences in non-coding regions of the PRNP gene but detection of similar genotypes in Canadian BSE field cases, that showed the expected brain pathology, suggested these differences may not be the primary cause of the abnormal result. Breed composition analysis showed a higher Hereford content in the abnormal steer as well as in two Canadian atypical BSE field cases and several additional abnormal experimental animals. This study could point towards a possible impact of breed composition on BSE pathogenesis.
机译:自牛海绵状脑病(BSE)发现以来,研究人员与受感染的脑材料具有口腔攻击性的牛,以研究疾病发病机制的各个方面。与大多数其他病原体不同,口头BSE挑战并不总是导致预期的临床介绍和病理学。在最近的一项研究中,带有BSE的口头和所有开发的临床症状挑战,并被处死和测试。然而,尽管孵化和临床介绍了,但其中一家阉圈在其大脑中没有可检测的PRP SC。分析来自这种动物的样品进行遗传差异以及体外PRP SC播种活性或感染性以确定这种动物的BSE状态以及它不同的原因。在异常转向的脑干中检测到播种活性,但比在正常的BSE阳性操纵子中发现的比例大约一百万倍。核化转基因小鼠的颅内挑战导致疾病的传播。异常转向在PRNP基因的非编码区中具有不同的遗传序列,但在加拿大BSE场病例中检测类似的基因型,显示出预期的脑病,建议这些差异可能不是异常结果的主要原因。品种成分分析显示出异常方向主的含量较高,以及两种加拿大非典型BSE场病例和几种另外的异常实验动物。本研究可以指出繁殖组合物对BSE发病机制可能的影响。

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