Shadow of prion protein (SPRN) is an interesting candidate gene thought to be involved in prion pathogenesis. In humans, an association has already been discovered between mutations in SPRN and the incidence of variant and sporadic Creutzfeldt-Jakob disease. However, in sheep, the effect of mutations in SPRN is largely unknown. Therefore, we analysed the presence of mutations in the entire ovine SPRN gene, their association with scrapie susceptibility and their effect on SPRN promoter activity. In total, 26 mutations were found: seven in the promoter region, four in intron 1, seven in the coding sequence and eight in the 3' untranslated region. The mutations detected in the coding sequence and the promoter region were subsequently analysed in more detail. In the coding sequence, a polymorphism causing a deletion of two alanines was found to be associated with susceptibility for classical scrapie in sheep. Furthermore, a functional analysis of deletion constructs of the ovine SPRN promoter revealed that the region 464 to 230 bp upstream of exon 1 (containing a putative AP-2 and putative Sp1 binding sites) is of functional importance for SPRN transcription. Six mutations in the SPRN promoter were also found to alter the promoter activity in vitro. However, no association between any of these promoter mutations and susceptibility for classical scrapie was found.

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Background: TSEs are a group of fatal neurodegenerative diseases occurring in man and animals. They are caused by prions, alternatively folded forms of the endogenous prion protein, encoded by PRNP. Since differences in the sequence of PRNP can not explain all variation in TSE susceptibility, there is growing interest in other genes that might have an influence on this susceptibility. One of these genes is SPRN, a gene coding for a protein showing remarkable similarities with the prion protein. Until now, SPRN has not been described in sheep, a highly relevant species in prion matters.

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Hypersensitivity to ivermectin and certain other drugs in Collies and related breeds is caused by a 4-base pair deletion mutation in the ABCB1 gene, better known as the MDR1 gene, encoding P-glycoprotein. There is no information available, however, regarding the presence of this mutation in dogs in Belgium. In this study, the ABCB1 genotype was assessed in 92 dogs of breeds suspected to possess the deletion mutation. The results indicated that the mutation was present in the Australian Shepherd, Collie, Shetland Sheepdog and Swiss White Shepherd, but was not detected in the Bearded Collies, Border Collies and German Shepherds of this study, which is in accordance with the findings in similar breed populations of other countries. In Belgium it is therefore important to take the ABCB1 genotype of the breeds involved into account, in order to use drugs in a safe and efficient manner and to improve the selection procedure in dog breeding. SAMENVATTINGDe overgevoeligheid van Collies en aanverwante rassen voor ivermectine en bepaalde andere geneesmiddelen wordt veroorzaakt door een deletiemutatie van 4 basenparen in het ABCB1-gen, beter bekend als het MDR1-gen, dat codeert voor P-glycoproteïne. Er is echter geen informatie beschikbaar omtrent de aanwezigheid van deze deletiemutatie bij honden in België. In deze studie werd het ABCB1-genotype bepaald bij 92 honden van verschillende rassen waarvan bekend is dat ze de mutatie kunnen bezitten. De deletiemutatie werd gevonden bij de Australische Herder, Collie, Sheltie en Zwitserse Witte Herder, maar was afwezig bij de Bearded Collies, Border Collies en de Duitse Herders van deze studie, wat overeenkomt met de resultaten van studies van soortgelijke populaties in andere landen. Voor een veilig en efficiënt gebruik van geneesmiddelen en bij de selectie in de hondenfokkerij is het daarom ook in België van belang rekening te houden met het ABCB1-genotype van de betrokken hondenrassen.