title: Disease characteristics of bovine spongiform encephalopathy following inoculation into mice via three different routes.
abstract: Mouse-adapted transmissible spongiform encephalopathy (TSE) strains are routinely distinguished based on reproducible disease characteristics in a given mouse line following inoculation via a consistent route. We investigated whether different administration routes (oral, intragastric (i.g.) and intracerebral (i.c.)) can alter the disease characteristics in IM mice after serial dilution of a stabilized mouse-adapted bovine spongiform encephalopathy (BSE) strain (301V). In addition, the infectivity of distal ileum and mesenteric lymph nodes (ln) sampled at three time points (35 days postinoculation (dpi), 70 dpi and terminal disease) after i.g. inoculation of 301V strain was assessed in mice by i.c. challenge. Strain characteristics were assessed according to standard methodology and PrP(Sc) immunohistochemistry deposition patterns. Mean incubation periods were prolonged following oral or i.g. inoculations compared to the i.c. route. Lesion profiles following i.c. challenges were elevated compared to i.g. and oral routes although vacuolation in the dorsal medulla was consistently high irrespective of the route of administration. Nevertheless, the same PrP(Sc) deposition pattern was associated with each route of administration. Distal and mesenteric ln infectivity was detected as early as 35 dpi and displayed consistent lesion profiles and PrP(Sc) deposition patterns. Our data suggest that although 301V retained its properties, some phenotypic parameters were affected by the route of inoculation. We conclude that bioassay data should be interpreted carefully and should be standardized for route of inoculation.
authors.affiliation: Animal Health and Veterinary Laboratories Agency (AHVLA) Weybridge, Addlestone, UK.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Vickery
authors.forename: Katy E
authors.initials: KE
authors.lastname: Beck
authors.forename: Marion M
authors.initials: MM
authors.lastname: Simmons
authors.forename: Stephen A C
authors.initials: SA
authors.lastname: Hawkins
authors.forename: John
authors.initials: J
authors.lastname: Spiropoulos
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002417:Cattle; D004195:Disease Models, Animal; D016643:Encephalopathy, Bovine Spongiform / Q000378:metabolism / Q000473:pathology* / Q000635:transmission*; D007082:Ileum / Q000378:metabolism / Q000473:pathology; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D018620:PrPSc Proteins / Q000378:metabolism; D011328:Prions / Q000008:administration & dosage* / Q000472:pathogenicity*; D013997:Time Factors
chemical_list: D018620:PrPSc Proteins; D011328:Prions
keywords: 301V; bovine spongiform encephalopathy; mouse bioassay; prion; transmissible spongiform encephalopathy
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