Ability of wild type mouse bioassay to detect bovine spongiform encephalopathy (BSE) in the presence of excess scrapie

Abstract

IntroductionScrapie and bovine spongiform encephalopathy (BSE) are transmissible spongiform encephalopathies (TSEs) which naturally affect small and large ruminants respectively. However, small ruminants, which are susceptible to BSE under experimental conditions, have been exposed to the same or similar contaminated food additives as cattle. To date two natural cases of BSE in small ruminants have been reported. As a result surveillance projects, combined with appropriate control measures, have been established throughout the European Union (EU) to minimize the overall incidence of small ruminant TSEs. Although BSE can be differentiated from classical scrapie (subsequently referred to as scrapie) if appropriate discriminatory tests are applied, the value of these tests in BSE/scrapie co-infection scenarios has not been evaluated fully. Mouse bioassay is regarded as the gold standard regarding differentiation of distinct TSE strains and has been used as to resolve TSE cases were laboratory tests produced equivocal results. However, the ability of this method to discriminate TSE strains when they co-exist has not been examined systematically. To address this issue we prepared in vitro mixtures of ovine BSE and scrapie and used them to challenge RIII, C57BL/6 and VM mice.ResultsDisease phenotype analysis in all three mouse lines indicated that most phenotypic parameters (attack rates, incubation periods, lesion profiles and Western blots) were compatible with scrapie phenotypes as were immunohistochemistry (IHC) data from RIII and C57BL/6 mice. However, in VM mice that were challenged with BSE/scrapie mixtures a single BSE-associated IHC feature was identified, indicating the existence of BSE in animals where the scrapie phenotype was dominant.ConclusionsWe conclude that wild type mouse bioassay is of limited value in detecting BSE in the presence of scrapie particularly if the latter is in relative excess.Electronic supplementary materialThe online version of this article (doi:10.1186/s40478-015-0194-2) contains supplementary material, which is available to authorized users.

Incomplete inactivation of atypical scrapie following recommended autoclave decontamination procedures

“…All dilutions of a single source were inoculated on the same day in reverse concentration order. Each mouse was inoculated intracerebrally with 20 µl of brain homogenate as described elsewhere (Corda et al, ). All animal procedures were performed according to the Animals (Scientific Procedures) Act 1986, Home Office License Number 70/6310.…”

Molecular characterisation of atypical BSE prions by mass spectrometry and changes following transmission to sheep and transgenic mouse models

“…Cattle and sheep were inoculated intracerebrally or orally in the context of previous studies, as described elsewhere [ 18 , 33 , 36 – 38 ]. Mice were inoculated intracerebrally with 20 μl of TSE inoculum prepared from single-brain material at 10% (w/v) in saline as described previously [ 45 ]. All animal procedures were conducted in accordance with the UK Animal (Scientific Procedures) Act 1986 under license from the Government Home Office (Project Licence numbers 70/6781, and 70/7167 and 70/6892, for ruminant and murine procedures, respectively).…”

Analysis of experimental mouse PRNP genetic polymorphisms and their susceptibility to prion diseases

“…On the other hand, there were no appropriate animal models or limited animal models for the drug development research (Fernandez-Borges et al, 2013, Ghate et al, 2014, Shirai et al, 2014. In the last 20 years, several mouse models had been established and were used in a number of research fields of prion diseases, including pathology (Corda et al, 2015, Ghate et al, 2014 and genetics (Asante et al, 2015, Friedman-Levi et al, 2011. Through the last 35 years, less than 50 different drugs have been tested in different experimental animal models without any hope for the results.…”