Codon 141 polymorphisms of the ovine prion protein gene affect the phenotype of classical scrapie transmitted from goats to sheep
Abstract Background A study to investigate transmission of classical scrapie via goat milk was carried out in sheep: firstly, lambs were challenged orally with goat scrapie brain homogenate to confirm transmission of scrapie from goats to sheep. In the second study phase, milk from scrapie-infected...
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| Format: | Article |
| Language: | English |
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BMC
2017-05-01
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| Series: | BMC Veterinary Research |
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| Online Access: | http://link.springer.com/article/10.1186/s12917-017-1036-1 |
| _version_ | 1818943754428481536 |
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| author | Timm Konold Laura J. Phelan Ben R. Donnachie Melanie J. Chaplin Saira Cawthraw Lorenzo González |
| author_facet | Timm Konold Laura J. Phelan Ben R. Donnachie Melanie J. Chaplin Saira Cawthraw Lorenzo González |
| author_sort | Timm Konold |
| collection | DOAJ |
| description | Abstract Background A study to investigate transmission of classical scrapie via goat milk was carried out in sheep: firstly, lambs were challenged orally with goat scrapie brain homogenate to confirm transmission of scrapie from goats to sheep. In the second study phase, milk from scrapie-infected goats was fed to lambs. Lambs were selected according to their prion protein gene (PRNP) genotype, which was either VRQ/VRQ or ARQ/ARQ, with or without additional polymorphisms at codon 141 (FF141, LF141 or LL141) of the ovine PRNP. This report describes the clinical, pathological and molecular phenotype of goat scrapie in those sheep that progressed to clinical end-stage. Results Ten sheep (six VRQ/VRQ and four ARQ/ARQ, of which three FF141 and one LL141) challenged with one of two scrapie brain homogenates, and six pairs of sheep (ARQ, of which five LL141 and seven LF141) fed milk from six different goats, developed clinical disease, which was characterised by a pruritic (all VRQ/VRQ and LL141 sheep) or a non-pruritic form (all LF141 and FF141 sheep). Immunohistochemical (IHC) examination revealed that the pattern of intra- and extracellular accumulation of disease-associated prion protein in the brain was also dependent on PRNP polymorphisms at codon 141, which was similar in VRQ and LL141 sheep but different from LF141 and FF141 sheep. The influence of codon 141 was also seen in discriminatory Western blot (WB), with LF141 and FF141 sheep showing a bovine spongiform encephalopathy-like profile (diminished reactivity with P4 antibody) on brain tissue. However, discriminatory WB in lymphoid tissues, and IHC pattern and profile both in lymphoid and brain tissue was consistent with classical scrapie in all sheep. Conclusions This study provided further evidence that the clinical presentation and the pathological and molecular phenotypes of scrapie in sheep are influenced by PRNP polymorphisms, particularly at codon 141. Differences in the truncation of disease-associated prion protein between LL141 sheep and those carrying the F141 allele may be responsible for these observations. |
| first_indexed | 2024-12-20T07:32:21Z |
| format | Article |
| id | doaj.art-8497f195e06f41fb9718e4b5ef3bf3bd |
| institution | Directory Open Access Journal |
| issn | 1746-6148 |
| language | English |
| last_indexed | 2024-12-20T07:32:21Z |
| publishDate | 2017-05-01 |
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| series | BMC Veterinary Research |
| spelling | doaj.art-8497f195e06f41fb9718e4b5ef3bf3bd2022-12-21T19:48:23ZengBMCBMC Veterinary Research1746-61482017-05-0113111310.1186/s12917-017-1036-1Codon 141 polymorphisms of the ovine prion protein gene affect the phenotype of classical scrapie transmitted from goats to sheepTimm Konold0Laura J. Phelan1Ben R. Donnachie2Melanie J. Chaplin3Saira Cawthraw4Lorenzo González5Animal Sciences Unit, Animal and Plant Health Agency WeybridgeAnimal Sciences Unit, Animal and Plant Health Agency WeybridgePathology Department, Animal and Plant Health Agency WeybridgePathology Department, Animal and Plant Health Agency WeybridgeCentral Sequencing Unit, Animal and Plant Health Agency WeybridgePathology Department, Animal and Plant Health Agency LasswadeAbstract Background A study to investigate transmission of classical scrapie via goat milk was carried out in sheep: firstly, lambs were challenged orally with goat scrapie brain homogenate to confirm transmission of scrapie from goats to sheep. In the second study phase, milk from scrapie-infected goats was fed to lambs. Lambs were selected according to their prion protein gene (PRNP) genotype, which was either VRQ/VRQ or ARQ/ARQ, with or without additional polymorphisms at codon 141 (FF141, LF141 or LL141) of the ovine PRNP. This report describes the clinical, pathological and molecular phenotype of goat scrapie in those sheep that progressed to clinical end-stage. Results Ten sheep (six VRQ/VRQ and four ARQ/ARQ, of which three FF141 and one LL141) challenged with one of two scrapie brain homogenates, and six pairs of sheep (ARQ, of which five LL141 and seven LF141) fed milk from six different goats, developed clinical disease, which was characterised by a pruritic (all VRQ/VRQ and LL141 sheep) or a non-pruritic form (all LF141 and FF141 sheep). Immunohistochemical (IHC) examination revealed that the pattern of intra- and extracellular accumulation of disease-associated prion protein in the brain was also dependent on PRNP polymorphisms at codon 141, which was similar in VRQ and LL141 sheep but different from LF141 and FF141 sheep. The influence of codon 141 was also seen in discriminatory Western blot (WB), with LF141 and FF141 sheep showing a bovine spongiform encephalopathy-like profile (diminished reactivity with P4 antibody) on brain tissue. However, discriminatory WB in lymphoid tissues, and IHC pattern and profile both in lymphoid and brain tissue was consistent with classical scrapie in all sheep. Conclusions This study provided further evidence that the clinical presentation and the pathological and molecular phenotypes of scrapie in sheep are influenced by PRNP polymorphisms, particularly at codon 141. Differences in the truncation of disease-associated prion protein between LL141 sheep and those carrying the F141 allele may be responsible for these observations.http://link.springer.com/article/10.1186/s12917-017-1036-1ScrapieTransmissionGoatSheepClinical pictureImmunohistochemistry |
| spellingShingle | Timm Konold Laura J. Phelan Ben R. Donnachie Melanie J. Chaplin Saira Cawthraw Lorenzo González Codon 141 polymorphisms of the ovine prion protein gene affect the phenotype of classical scrapie transmitted from goats to sheep BMC Veterinary Research Scrapie Transmission Goat Sheep Clinical picture Immunohistochemistry |
| title | Codon 141 polymorphisms of the ovine prion protein gene affect the phenotype of classical scrapie transmitted from goats to sheep |
| title_full | Codon 141 polymorphisms of the ovine prion protein gene affect the phenotype of classical scrapie transmitted from goats to sheep |
| title_fullStr | Codon 141 polymorphisms of the ovine prion protein gene affect the phenotype of classical scrapie transmitted from goats to sheep |
| title_full_unstemmed | Codon 141 polymorphisms of the ovine prion protein gene affect the phenotype of classical scrapie transmitted from goats to sheep |
| title_short | Codon 141 polymorphisms of the ovine prion protein gene affect the phenotype of classical scrapie transmitted from goats to sheep |
| title_sort | codon 141 polymorphisms of the ovine prion protein gene affect the phenotype of classical scrapie transmitted from goats to sheep |
| topic | Scrapie Transmission Goat Sheep Clinical picture Immunohistochemistry |
| url | http://link.springer.com/article/10.1186/s12917-017-1036-1 |
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