Prion diseases are progressive and fatal, neurodegenerative disorders described in humans and animals. According to the "protein-only" hypothesis, the normal host-encoded prion protein (PrPC) is converted into a pathological and infectious form (PrPSc) in these diseases. Transgenic knockout models have shown that PrPC is a prerequisite for the development of prion disease. In Norwegian dairy goats, a mutation (Ter) in the prion protein gene (PRNP) effectively blocks PrPC synthesis. We inoculated 12 goats (4 PRNP+/+, 4 PRNP+/Ter, and 4 PRNPTer/Ter) intracerebrally with goat scrapie prions. The mean incubation time until clinical signs of prion disease was 601 days post-inoculation (dpi) in PRNP+/+ goats and 773 dpi in PRNP+/Ter goats. PrPSc and vacuolation were similarly distributed in the central nervous system (CNS) of both groups and observed in all brain regions and segments of the spinal cord. Generally, accumulation of PrPSc was limited in peripheral organs, but all PRNP+/+ goats and 1 of 4 PRNP+/Ter goats were positive in head lymph nodes. The four PRNPTer/Ter goats remained healthy, without clinical signs of prion disease, and were euthanized 1260 dpi. As expected, no accumulation of PrPSc was observed in the CNS or peripheral tissues of this group, as assessed by immunohistochemistry, enzyme immunoassay, and real-time quaking-induced conversion. Our study shows for the first time that animals devoid of PrPC due to a natural mutation do not propagate prions and are resistant to scrapie. Clinical onset of disease is delayed in heterozygous goats expressing about 50% of PrPC levels.

中文翻译：

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自然不含PrPC的山羊具有抗瘙痒性。

on病毒是人类和动物中描述的进行性和致命性神经退行性疾病。根据“仅蛋白质”假说，正常的宿主编码病毒蛋白（PrPC）在这些疾病中转化为病理和传染性形式（PrPSc）。转基因敲除模型表明，PrPC是发展病毒疾病的先决条件。在挪威奶山羊中，病毒蛋白基因（PRNP）中的突变（Ter）有效地阻止了PrPC的合成。我们在大脑内接种了12只山羊（4只PRNP + / +，4只PRNP + / Ter和4只PRNPTer / Ter）和山羊瘙痒病pr病毒。PRNP + / +山羊中直到until病毒疾病临床症状的平均潜伏时间是接种后601天（dpi），PRNP + / Ter山羊是773 dpi。PrPSc和空泡化相似地分布在两组的中枢神经系统（CNS）中，并在所有脑区域和脊髓节段中观察到。通常，PrPSc的积累在外周器官中受到限制，但是所有PRNP + / +山羊和4只PRNP + / Ter山羊中的1只在头部淋巴结中均为阳性。四只PRNPTer / Ter山羊保持健康，没有clinical病毒疾病的临床迹象，并被安乐死1260 dpi。如预期的那样，通过免疫组织化学，酶免疫测定和实时地震诱导的转化评估，在该组的CNS或外周组织中未观察到PrPSc的积累。我们的研究首次表明，由于自然突变而缺乏PrPC的动物不会繁殖ions病毒，并且对瘙痒病具有抵抗力。