PrP polymorphisms and their effect on the TSE susceptibility in goats.

Martin Groschup, K Tauscher, E Soto, Martin Eiden, Jan Langeveld, Alex Bossers, F Lantier, F Barrilet, Wilfred Goldmann, Olivier Andreoletti, J M Torres, Christine Fast

Research output: Contribution to conferenceAbstract

Abstract

The susceptibility of sheep for classical scrapie and BSE prions is strongly linked to polymorphisms in the prion gene/protein. Therefore breeding programs were implemented in EU member states to select for genetically resistant sheep. In contrast only few epidemiological and genetic data were available until recently on the molecular factors modulating the TSE susceptibility in goats. Several PrP polymorphisms are known in the caprine prion gene/protein, which have potential to impact the convertability of prion protein. We have therefore carried out cell-free conversion studies with naturally found caprine prion polymorphisms of putatively lower TSE susceptibility. For this purpose prion proteins were expressed as recombinant proteins and exposed to murine BSE or scrapie strains as well as bovine, ovine and caprine BSE and caprine scrapie isolates.
Moreover, the most likely polymorphism candidates for conferring BSE resistance were tested in the frame of a EU-funded BSE challenge and serial time kill study with goats. Following an oral challenge with goat passaged BSE homogenate, animals were clinically assessed after given time points. Moreover, biopsies of tonsil and rectal mucosal and necropsies were performed periodically. Goats were euthanized at defined time points and samples from the lymphoreticular, the central and peripheral nervous system and the placenta and milk were collected and examined histopathologically, immunohistochemically, by immunoblot and/or transgenic mouse bioassay. These investigations revealed that the BSE pathogenesis in goats is not as widespread as seen for example in scrapie in sheep and goats or ovine BSE. Moreover, these studies show that PRNP polymorphism Q/K 222 is strongly associated with an increased but possibly not absolute resistance to BSE under experimental conditions. Together with data from other experiments/groups these data hold promise for future breeding programs for genetically TSE-resistant goats.
Original languageEnglish
Publication statusPublished - 3 Dec 2014
Event3rd Iberian Congress on Prions - Faucltad de Veterinaria, Zaragoza, Spain
Duration: 2 Dec 20143 Dec 2014

Conference

Conference3rd Iberian Congress on Prions
CountrySpain
CityZaragoza
Period2/12/143/12/14

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