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Inoculation of BARBs into transgenic mice to examine differences to BSE cases born before and after feed bans - SE1867

• The bovine spongiform encephalopathy (BSE) epidemic in Great Britain (GB) peaked with 36,682 cases in 1992 before declining to 53 cases in 2007, eleven cases in 2010 and 3 cases so far in 2011. The GB epidemic has been largely controlled by the ban on feeding ruminant-derived protein to ruminants introduced in July 1988 as evidenced by the peak infected birth cohort. However, by 1991 it was clear that the 1988 ban was not completely effective. The risk of exposure was further reduced by the ban on the feeding of mammalian protein to ruminants in 1994 and the ban on the feeding of mammalian meat and bone meal to farmed livestock in April 1996. However, these bans were again not completely effective due to the belief that there was still cross-contamination at very low levels, particularly associated with imported feed. In January 2001, the European Union banned the feeding of processed animal protein to farmed animals. Animals born after these two reinforced bans (1996 and 2001) are termed BARBs. There have been 174 such cases reported since 2000 which peaked in 2003 with 38 cases. Since then the number of BARB BSE cases have declined to single figures (2 in 2009, 5 in 2010 and so far there have been 3 cases in 2011).
• The classical form of BSE is generally considered to have been caused by a single prion strain (C-BSE) but since 2003 at least two strain variants of cattle prion disorders have been recognized and classified as atypical forms of C-BSE (H-BSE and L-BSE) which show differences in vacuolation and molecular profiles to C-BSE. The two GB BSE cases detected in 2011 were born in 1998 and 1999 and have been reported as BARB L-BSE cases whereas all previous BARB BSE cases have been reported as C-BSE cases.
• Although there are complete test data-sets for some BARB BSE cases, poor tissue condition and in some cases autolysis have largely ruled out complete comparisons with non-BARB BSE cases. Initially, In the Defra funded project SE2014, three samples were intracerebrally inoculated into 4 different mouse lines (AHVLA developed transgenic mouse lines, Tg(BoPrP)1896 and Tg(OvPrPAHQ) EM16, Tg bov 110 imported from Spain and the wild type RIII mice). One case is a BARB BSE case born in 1999 and two are cases both born in 2003. Approved extended objectives for SE2014 have resulted in two further BARB BSE cases born in 2004 being inoculated and the two BARB L-type BSE cases detected in 2011.
• This present proposal is aimed at collecting more data for BARB BSE cases by extending the transgenic mouse inoculations to nine remaining BARBs, born between 1996 and 2000, and to six more BARB cases, three born in 2001 and three born in 2002, alongside three more C-BSE controls. The analyses of mouse brains will include: incubation period, lesion and molecular profiling, and prion protein distribution by immuohistochemistry (IHC) to look for any differences between BARBs and BSE cases which were not BARBs.
Objective 1. Acquisition and microbial decontamination of brain material from the fifteen BARB cases and the controls by 1st January 2013.

Objective 1.1. Breeding of sufficient mice and intracerebral inoculation into each particular Tg mouse line. To be completed by 31sh August 2014

Objective 1.2. Analysis of incubation period, lesion and molecular profiling, and prion protein distribution for each mouse line (estimated end dates for incubation period after challenge are 14 -16 months (Tg(BoPrP) 1896) and 10 – 12 months (Tgbo110 and Tg(OvPrP) EM16). All analyses completed 31st May 2015

Objective 1.3. Compilation of comparative data within the project and data obtained for between-project comparisons. Final report to customer and submission of publications. 30th September 2015.
Time-Scale and Cost
From: 2012

To: 2016

Cost: £450,630
Contractor / Funded Organisations
Veterinary Laboratories Agency (VLA)
Fields of Study
Animal Health