title: Regional heterogeneity of cellular prion protein isoforms in the mouse brain.
abstract: Prion diseases are a group of invariably fatal neurodegenerative disorders that include Creutzfeldt-Jakob disease in humans, scrapie in sheep and goats, and bovine spongiform encephalopathy in cattle. The infectious agent or prion is largely composed of an abnormal isoform (PrPSc) of a host encoded normal cellular protein (PrPc). The conversion of PrPc to PrPSc is a dynamic process and, for reasons that are not clear, the distribution of spongiform change and PrPSc deposition varies among prion strains. An obvious explanation for this would be that the transformation efficiency in any given brain region depends on favourable interactions between conformations of PrPc and the prion strain being propagated within it. However, identification of specific PrPc conformations has until now been hampered by a lack of suitable panels of antibodies that discriminate PrPc subspecies under native conditions. In this study, we show that monoclonal antibodies raised against recombinant human prion protein folded into alpha or beta conformations exhibit striking heterogeneity in their specificity for truncations and glycoforms of mouse brain PrPc. We then show that some of these PrPc isoforms are expressed differentially in certain mouse brain regions. This suggests that variation in the expression of PrPc conformations in different brain regions may dictate the pattern of PrPSc deposition and vacuolation, characteristic for different prion strains.
authors.affiliation: CNS Infection and Immunity Group, and Department of Neurogenetics, Imperial College, Norfolk Place, London W2 1PG, UK.
authors.forename: Vincent
authors.initials: V
authors.lastname: Beringue
authors.forename: Gary
authors.initials: G
authors.lastname: Mallinson
authors.forename: Maria
authors.initials: M
authors.lastname: Kaisar
authors.forename: Mourad
authors.initials: M
authors.lastname: Tayebi
authors.forename: Zahid
authors.initials: Z
authors.lastname: Sattar
authors.forename: Graham
authors.initials: G
authors.lastname: Jackson
authors.forename: David
authors.initials: D
authors.lastname: Anstee
authors.forename: John
authors.initials: J
authors.lastname: Collinge
authors.forename: Simon
authors.initials: S
authors.lastname: Hawke
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001921:Brain / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D018604:Epitope Mapping; D006031:Glycosylation; D051379:Mice; D008815:Mice, Inbred Strains; D018621:PrPC Proteins / Q000276:immunology / Q000378:metabolism*; D011233:Precipitin Tests; D020033:Protein Isoforms / Q000276:immunology / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D018621:PrPC Proteins; D020033:Protein Isoforms