Tissue distribution of pathological prion protein and infectivity in orally BSE infected goats of different genotypes.

Background/Introduction:
Two natural cases of BSE infected goats have been identified so far, but only limited data are known concerning a genotype dependent spread of pathological prion protein (PrPD)/infectivity as well as transmission routes within the herds. The data presented here are important for both the development of future breeding programs and for public health protections measures.

Material and Methods:
Groups of three goats carrying five PRNP genotypes with decreasing susceptibility to Scrapie (I142R211Q222/IRQ: wild type (WT), MRQ/IRQ (IM142), MRQ/MRQ (MM142), IRQ/IQQ: (RQ211) and IRQ/IRK: (QK222)) were orally challenged with cattle (INRA) or goat (Roslin) derived BSE and sequentially culled at 6, 12, 17-18, and 24-26, 28-36, 44-46 months post-inoculation (mpi). Additionally 19 goat kids of different genotypes were bred and five horizontal control goats (WT) were kept within the herd. Together about 140 goats have been included. At necropsies, a large number of samples were taken for the detection of PrPD (IHC, ELISA, WB) and of infectivity (transgenic mouse bioassays).

Results:
Only traces of PrPD were detectable in Peyer`s patches, autonomous (ANS) and central (CNS) nervous system in WT and RQ211 goats up to 17 mpi. The first clinical symptoms were observed in 9 WT goats after 24-26 mpi, in 5 RQ211 goats after 28-36 mpi and in two IM142 goats after 45 mpi. The clinically affected goats revealed high amounts of PrPD in the ANS/ENS and CNS, but only limited amounts in the lymphoreticular system and in the muscles. Additionally, infectivity was present in the peripheral nerves, muscles, mammary gland, spleen and tongue of a clinically affected WT goat. Up to now only two QK222 goats showed signs of a BSE infection, confined to the CNS. PrPD deposits were seen in one goat killed 43 mpi and traces of infectivity in another goat killed 45 mpi. Furthermore, neither horizontal control goats nor placenta and goat kids showed any signs of a BSE infection.

Conclusion:
A clear influence of the goat genotype on susceptibility to BSE is demonstrated. Invasion of the CNS was very late in QK222 goat and two goats are still alive 65 months after infection. Although clinical goats showed a wide distribution of PrPD and/or infectivity, vertical and horizontal transmission routes seem to be of minor relevance. However, infectivity studies of dam tissues in transgenic mice are ongoing, including milk.

This work was supported by EU-project FOOD-CT-2006-36353, and by national fundings in the different partner`s countries.