Generation of human chronic wasting disease in transgenic mice
| العنوان: | Generation of human chronic wasting disease in transgenic mice |
|---|---|
| المؤلفون: | Justin J. Greenlee, Zerui Wang, Manuel V. Camacho, Ignazio Cali, Wen-Quan Zou, Kefeng Qin, Pingping Shen, Qingzhong Kong, Jue Yuan, James A. Mastrianni |
| المصدر: | Acta Neuropathologica Communications, Vol 9, Iss 1, Pp 1-11 (2021) Acta Neuropathologica Communications |
| بيانات النشر: | Springer Science and Business Media LLC, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Genetically modified mouse, PrPSc Proteins, animal diseases, Bovine spongiform encephalopathy, Prion disease, Mice, Transgenic, Cellular prion protein (PrPC), Biology, Chronic wasting disease (CWD), Serial protein misfolding cyclic amplification (sPMCA), Pathology and Forensic Medicine, Mice, Cellular and Molecular Neuroscience, Zoonoses, medicine, Animals, Humans, PrPC Proteins, RC346-429, Research, Deer, Human brain, Chronic wasting disease, medicine.disease, Virology, In vitro, nervous system diseases, Blot, Disease Models, Animal, Prions (PrPSc), medicine.anatomical_structure, nervous system, biology.protein, Wasting Disease, Chronic, Protein Misfolding Cyclic Amplification, Neurology. Diseases of the nervous system, Neurology (clinical), Antibody |
| الوصف: | Chronic wasting disease (CWD) is a cervid prion disease caused by the accumulation of an infectious misfolded conformer (PrPSc) of cellular prion protein (PrPC). It has been spreading rapidly in North America and also found in Asia and Europe. Although bovine spongiform encephalopathy (i.e. mad cow disease) is the only animal prion disease known to be zoonotic, the transmissibility of CWD to humans remains uncertain. Here we report the generation of the first CWD-derived infectious human PrPSc by elk CWD PrPSc-seeded conversion of PrPC in normal human brain homogenates using in vitro protein misfolding cyclic amplification (PMCA). Western blotting with human PrP selective antibody confirmed that the PMCA-generated protease-resistant PrPSc was derived from the human PrPC substrate. Two lines of humanized transgenic mice expressing human PrP with either Val or Met at the polymorphic codon 129 developed clinical prion disease following intracerebral inoculation with the PMCA-generated CWD-derived human PrPSc. Diseased mice exhibited distinct PrPSc patterns and neuropathological changes in the brain. Our study, using PMCA and animal bioassays, provides the first evidence that CWD PrPSc can cross the species barrier to convert human PrPC into infectious PrPSc that can produce bona fide prion disease when inoculated into humanized transgenic mice. |
| تدمد: | 2051-5960 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::347c202114890e296dedfd91ab35c0c9Test https://doi.org/10.1186/s40478-021-01262-yTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....347c202114890e296dedfd91ab35c0c9 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20515960 |
|---|