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 PrPSc 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 PrPSc 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 PrPSc 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.

Distinct Transmissibility Features of TSE Sources Derived from Ruminant Prion Diseases by the Oral Route in a Transgenic Mouse Model (TgOvPrP4) Overexpressing the Ovine Prion Protein

“…As this was revealed by further passage in bovine transgenic mice in this last study, strain typing from our orally infected mice showing altered PrPres features will require further passage by intracerebral route in an appropriate experimental model as it has been well established that the route of infection can strongly influence the apparent phenotype of a TSE strain [32], [33].…”

Assessing the Susceptibility of Transgenic Mice Overexpressing Deer Prion Protein to Bovine Spongiform Encephalopathy

“…At necropsy, the brain of each mouse was removed and cut parasagitally into two parts. The larger part was fixed in buffered formalin and processed for histology to detect and semiquantitatively assess spongiosis to produce lesion profiles (17). Fixed material was also assessed by immunohistochemistry (IHC) using Rb486 antibody for detection of the PrP Sc distribution in the brain (18,19).…”

Detection of Pathognomonic Biomarker PrPSc and the Contribution of Cell Free-Amplification Techniques to the Diagnosis of Prion Diseases

“…Regarding the time course of PrP Sc deposition in CNS during the pre-symptomatic stage of the disease, it has been thoroughly studied in animal models of acquired prion disease. Thus, the time course of PrP Sc spreading from peripheral tissues to the CNS has been characterized in several models of infection [47][48][49][50][51][52][53][54] and even distinctive deposition patterns were found after injection of the same prions through different routes [55][56][57]. However, there are few reports trying to unravel the time course of PrP Sc deposition in sporadic and genetic forms of the disease, which are the vast majority in humans.…”