HECTD2 is associated with susceptibility to mouse and human prion disease
Prion diseases are fatal transmissible neurodegenerative disorders, which include Scrapie, Bovine Spongiform Encephalopathy (BSE), Creutzfeldt-Jakob Disease (CJD), and kuru. They are characterised by a prolonged clinically silent incubation period, variation in which is determined by many factors, i...
| Main Authors: | , , , , , , , , , , |
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| Format: | Journal Article |
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Public Library of Science
2009
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| Online Access: | http://hdl.handle.net/20.500.11937/14760 |
| _version_ | 1848748709578276864 |
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| author | Lloyd, S. Maytham, E. Pota, H. Grizenkova, J. Molou, E. Uphill, J. Hummerich, H. Whitfield, J. Alpers, Michael Philip Mead, S. Collinge, J. |
| author_facet | Lloyd, S. Maytham, E. Pota, H. Grizenkova, J. Molou, E. Uphill, J. Hummerich, H. Whitfield, J. Alpers, Michael Philip Mead, S. Collinge, J. |
| author_sort | Lloyd, S. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | Prion diseases are fatal transmissible neurodegenerative disorders, which include Scrapie, Bovine Spongiform Encephalopathy (BSE), Creutzfeldt-Jakob Disease (CJD), and kuru. They are characterised by a prolonged clinically silent incubation period, variation in which is determined by many factors, including genetic background. We have used a heterogeneous stock of mice to identify Hectd2, an E3 ubiquitin ligase, as a quantitative trait gene for prion disease incubation time in mice. Further, we report an association between HECTD2 haplotypes and susceptibility to the acquired human prion diseases, vCJD and kuru. We report a genotype-associated differential expression of Hectd2 mRNA in mouse brains and human lymphocytes and a significant up-regulation of transcript in mice at the terminal stage of prion disease. Although the substrate of HECTD2 is unknown, these data highlight the importance of proteosome-directed protein degradation in neurodegeneration. This is the first demonstration of a mouse quantitative trait gene that also influences susceptibility to human prion diseases. Characterisation of such genes is key to understanding human risk and the molecular basis of incubation periods. © 2009 Lloyd et al. |
| first_indexed | 2025-11-14T07:09:21Z |
| format | Journal Article |
| id | curtin-20.500.11937-14760 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T07:09:21Z |
| publishDate | 2009 |
| publisher | Public Library of Science |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-147602017-09-13T15:03:20Z HECTD2 is associated with susceptibility to mouse and human prion disease Lloyd, S. Maytham, E. Pota, H. Grizenkova, J. Molou, E. Uphill, J. Hummerich, H. Whitfield, J. Alpers, Michael Philip Mead, S. Collinge, J. Prion diseases are fatal transmissible neurodegenerative disorders, which include Scrapie, Bovine Spongiform Encephalopathy (BSE), Creutzfeldt-Jakob Disease (CJD), and kuru. They are characterised by a prolonged clinically silent incubation period, variation in which is determined by many factors, including genetic background. We have used a heterogeneous stock of mice to identify Hectd2, an E3 ubiquitin ligase, as a quantitative trait gene for prion disease incubation time in mice. Further, we report an association between HECTD2 haplotypes and susceptibility to the acquired human prion diseases, vCJD and kuru. We report a genotype-associated differential expression of Hectd2 mRNA in mouse brains and human lymphocytes and a significant up-regulation of transcript in mice at the terminal stage of prion disease. Although the substrate of HECTD2 is unknown, these data highlight the importance of proteosome-directed protein degradation in neurodegeneration. This is the first demonstration of a mouse quantitative trait gene that also influences susceptibility to human prion diseases. Characterisation of such genes is key to understanding human risk and the molecular basis of incubation periods. © 2009 Lloyd et al. 2009 Journal Article http://hdl.handle.net/20.500.11937/14760 10.1371/journal.pgen.1000383 Public Library of Science unknown |
| spellingShingle | Lloyd, S. Maytham, E. Pota, H. Grizenkova, J. Molou, E. Uphill, J. Hummerich, H. Whitfield, J. Alpers, Michael Philip Mead, S. Collinge, J. HECTD2 is associated with susceptibility to mouse and human prion disease |
| title | HECTD2 is associated with susceptibility to mouse and human prion disease |
| title_full | HECTD2 is associated with susceptibility to mouse and human prion disease |
| title_fullStr | HECTD2 is associated with susceptibility to mouse and human prion disease |
| title_full_unstemmed | HECTD2 is associated with susceptibility to mouse and human prion disease |
| title_short | HECTD2 is associated with susceptibility to mouse and human prion disease |
| title_sort | hectd2 is associated with susceptibility to mouse and human prion disease |
| url | http://hdl.handle.net/20.500.11937/14760 |